acros organics acta n°009

7/28/2019 Acros Organics acta N009

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Acros Organics journalfor chemists

Spring 2002

Acros Organics

actaacta

Acros Organics journalfor chemists

Spring 2002

Acros Organics

A Brief Overview ofCyclopropane Aminoacids . . . . . . . . . 1Nick Kilenyi

Organic Peroxides inRadical Synthesis Reactions . . . . . . . . 6J. Meijer, A.H. Hogt and B. Fischer

(S)- and (R)-N-Boc-N, O-Iso-propylidene--methylserinals . . . . . . . 9

A. Avenozaa, C. Cativielab, F. Corzanaa, J. M.Peregrinaa, D. Sucunzaa and M. M. Zurbanoa

99 ChiroTechproduct range now availableexclusively through Acros Organics

ChiroTechproduct range now availableexclusively through Acros Organics


2/20

More product documentationfor your research

Recent product infosheetsN 50: HEB, (S)-Ethyl 3-hydroxybutyrate,

a next building block for asymmetrical

synthesis

N 51: Sodium polytungstate, the NON-TOXIC

alternative high density solvent for sink-

float analysis

N 52: Chiral Glycidols

You can find more infosheets in the

"product info" department of the library

on our website www.acros.com

Chemistry review printsN 1: Solid Phase synthesis of compound libraries

and their application in drug discovery.

N 2: From homogeneous to heterogeneouscatalysis, recent advantages in asymmetricsynthesis with nitrogen containing ligands.

N 3: 1-Hydroxycyclopropanecarboxylic acid -a readily available and efficient precursor.

N 4: Silylated N-Tert-Butyl Aldimines: Versatileorganosilicon reagents for polyenalsynthesis.

N 5:A complete range (C2 to C20) of fullysynthetic sphingosines and ceramides.

No 6: Organic Peroxides in Radical SynthesisReactions.

No 7: CuCl(OH).TMEDA: A Novel, EfficientCatalyst for Aerobic Oxidative CouplingReactions.

NEW No 8: The wonderful world of the

bis(trimethylsilyl) ketene acetalreagents

New publicationsChirals CD

12 more suggestionsfor the Organic Chemist

Drug Discovery brochure

Solid Phase Synthesis brochure

Ionic liquids handbook

Much has happened since the last issue of

Acros Organics Acta. We see new trends

emerging every day, inside as well as outside

the chemistry lab. These are veryinteresting times for a company like Acros

Organics, and we are working hard to keep

apace with all these trends.

Our site in Belgium, for instance, witnessed

an impressive expansion with the building of

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logues that we published contain more than

2000 new additions, and more products are

added every day.

We initiated important collaboration projects

with ChiroTech for our drug discovery product

line, and with QUILL for ionic liquids, which

play an important role in green chemistry.

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ties in this issue of the Acta.

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ACROS ORGANICSGeel West Zone 2, Janssen Pharmaceuticalaan 3a

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First words


3/20

Introduction

Cyclopropane aminoacids are defined for the purposeof this article as alpha-aminoacids with a bridgingmethylene group forming a cyclopropyl ring.

There are two main families, colloquially named 2,3-methanoaminoacids (1) in which the bridge is connected to thealpha-carbon, and 3,4-methanoaminoacids (2), in which it is oneposition further down the chain. Such compounds are of interest asnatural products, and also as conformationally-restricted analogues ofthe proteinogenic aminoacids. It should be noted that substituted 2,3-

methanoaminoacids can exist in two diastereomeric forms, with thesubstituent either synor anti to the nitrogen. No attempt has beenmade here to provide a comprehensive review of this important field.Instead, emphasis has been placed on the more recent work. Readersdesirous of greater detail should consult the excellent review pub-lished in 1990 by Stammer (ref 1), and the original papers cited here.

Naturally-Occurring CyclopropaneAminoacids

The simplest, and perhaps most important cyclopropane aminoacid isthe parent, 1-aminocyclopropane-1-carboxylic acid (3) (Acc). Thiscompound, originally isolated from apples and pears, is the biogenet-ic precursor of the ripening hormone ethylene in plants. (ref 2)

Coronamic acid (4, R=Et) is a component of the toxins coronatine (5), aplant toxin produced by Pseudomonas corona-facience. The lowerhomologue norcoronamic acid (R=Me) is found in norcoronatine. (ref 3)

Hypoglycine A and B (6), isolated from the Ackee fruit Blighia sapi-da, cause hypoglycaemia in Man and animals. (ref 4)

Applications of CyclopropaneAminoacids

As alluded to above, cyclopropane aminoacids may be regarded asconformationally frozen analogues of the natural aminoacids. It is

therefore of great interest to incorporate them in peptides in order toprobe conformational spaces and reactivity. Enkephalins containing2,3-methanophenylalanine showed very different binding affinitiesand selectivities compared with the native hormone. Furthermore,such peptides were resistant to hydrolysis by chymotrypsin and car-boxypeptidase Y. (ref 5) The dipeptides N-benzoyl-Acc-Phe-OH andN-benzoyl-Acc-Pro-OH inhibited carboxypeptidase A in a time-dependent manner indicative of irreversible covalent binding of thedipeptide to the enzyme. (ref 6) Incorporation of Acc into peptidesfavours folding of the backbone into a C-7 helix or a gamma-turn,unlike the acyclic aminoisobutyric acid residue Aib. (ref 7)

A Brief Overview of Cyclopropane Aminoacids

NH3+

CO2-

H H

HH

Plants

(3)

NH3+

CO2-

R

NH

CO2H

R

O

H

H

OMe

(4)

(5)

CO2-

H3N H

(6)

+

Acros Organics Acta 9 - Spring 2002 1

NH3+

CO2-

H

R

NH3+

CO2-

R

H

(syn) (anti) (1)

H3N

H

CO2 (2)

Nick KilenyiCerise Chemtech sa/nv, Rue de Strasbourg 5,

Da Vinci Science Park, B-1140 Brussels, Belgium.


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References1. Stammer, C. H. Tetrahedron1990, 46, 2231

2. Fowden, L.; Lea, P. J.; Bell, E. J., The Non-Protein Aminoacids of Plants, Advancesin Enzymology, ed. A. Meister, Wiley, New York, 1979, 117

3. Ichihara, A.,;Shiraishi, K.; Sato, H.; Sakamura,; S. Nishiyama, K.; Sakai, R.; Furusaki,A.; Matsumoto, T.J. Am. Chem. Soc. 1977, 99, 636

4. Eloff, J.N.; Fowden, L. Phytochemistry1970, 9, 2423 and references therein

5. Mapelli, C.; Kimura, H.; Stammer, C. H. Int.J. Peptide Protein Res. 1986, 28, 347

6. Ner, S. K.; Suckling. C. J.; Bell, A. R.; Wrigglesworth, R. J.J. Chem. Soc. Chem.Commun. 1987, 480

7. Barone, V.; Franternali, B.; Cristinziano, P. L.; Lelj, F.; Rosa, A. Biopolymers1988,27, 1673.

Acros Organics Acta 9 - Spring 20022

N

OH

O

O

O

CH3

CH3

CH3

N

OH

O

O

O

CH3

CH3

CH3

11162 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Cyclopropanecarboxylic acid 98%

11163 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Cyclopropanecarboxylic acid chloride 98%

34528 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1,1-Cyclopropanedicarboxylic acid 98%

11835 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Ethyl cyclopropanecarboxylate 99%

12671 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Methyl cyclopropanecarboxylate 98%

13046 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .trans-2-Phenylcyclopropane-1-carboxylic acid 95%

13492 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1-(2,4-Dichlorophenyl)cyclopropanecarboxylic acid 95%

16445 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Diethyl 1,1-cyclopropanedicarboxylate 97%

17059 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1-Phenyl-1-cyclopropanecarbonitrile 97%

17068 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1-Phenyl-1-cyclopropanecarboxylic acid 97%

17069 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1-(4-Chlorophenyl)-1-cyclopropanecarboxylic acid 99%

19816 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2-Methylcyclopropanecarboxylic acid 98%

20529 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .DL-3-Methylenecyclopropane-trans-1,2-dicarboxylic acid 98%

25534 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Dimethyl cis-1,2-cyclopropanedicarboxylate 98%

27850 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Dimethyl 1-methyl-trans-1,2-cyclopropanedicarboxylate 99+%

27851 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Dimethyl 3-methyl-trans-1,2-cyclopropanedicarboxylate 99%

30142 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1-Amino-1-cyclopropanecarboxylic acid 99%

30143 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1-Hydroxy-1-cyclopropanecarboxylic acid 98%

23305 . . . . . . . . . . . . . . . . . . . . . .Methyl 3-(2,2-dichlorovinyl)-2,2-dimethyl-(1-cyclopropane)carboxylate, cis/trans 99%

27520 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Methyl (1R,3S)-2,2-dimethyl-3-(2-oxopropyl)-cyclopropaneacetate 96%30211 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Methyl 1-hydroxy-1-cyclopropane carboxylate

30963 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1-(Aminocarbonyl)-1-cyclopropanecarboxylic acid 97%

33530 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Ethyl 1-hydroxycyclopropanecarboxylate 90%

ADDITIONAL CYCLOPROPANE CARBOXYLIC ACIDS AND DERIVATIVES

Acros Organics Offer: NEW Cyclopropane amino acids

35380

(1R,2R)-N-BOC-1-Amino-2-

phenylcyclopropanecarboxylic

acid

35381

(1R,2S)-N-BOC-1-Amino-2-


acid

N

OH

O

O

O

CH3

CH3

CH3

N

OH

O

O

O

CH3

CH3

CH3

35379

(1S,2S)-N-BOC-1-Amino-2-


acid

35382

(1S,2R)-N-BOC-1-Amino-2-


acid

A Brief Overview ofCyclopropane AminoacidsNick Kilenyi

Cerise Chemtech sa/nv, Rue de Strasbourg 5,Da Vinci Science Park, B-1140 Brussels, Belgium.


5/20

Universit de Cergy-Pontoise,Laboratoire de Synthse Organomtallique associ au CNRS,

5 mail Gay Lussac, Neuville sur Oise, F-95031 Cergy-Pontoise Cedex


Since the work of Mukaiyama1 in 1974 on the aldol reaction using silylenol ethers, silylketene acetals have seen an explosive growth in their useas building blocks in organic synthesis. Among these new reagents, bis (trimethylsilyl) ketene acetals are now the organosilicon compounds ofchoice for type aldol condensations because of their ease of preparation, clean products and high selectivity.

The direct homologation of aldehydes into unsaturated conjugated carboxylic acids with the introduction of two carbon atoms in the resultingchain is a very attractive reaction, since polyethylenic carboxylic acids are very useful intermediates in the total synthesis of natural products.

Indeed, the condensation of reagent 33101 with a wide range of aldehydes in the presence of catalytic amount of catalyst takes place at roomtemperature to give the corresponding ,-ethylenic carboxylic acids in excellent yield and with a total E stereoselectivity2,3. Reagent 33105 hasproven to be suitable for one pot four-carbon homologation of aldehydes4 and imines5. Silylated acetate6 33112 and crotonate7 33111 can be usedfor the construction of many important building blocks.

Queen Substance of honeybee was selected as a targetfor total synthesis of a natural product with the aim todemonstrate the utility of our organosilicon reagents.The following retrosynthetic scheme represents themost efficient total synthesis described up today. Thus,the Queen Substance has been prepared in seven stepsin 34% over yield8.

(1) Mukaiyama, T.; Banno, K.; Narasaka, K. J. Am. Chem. Soc. 1974, 96,7503.

(2) Bellassoued,M.; Gaudemar, M. Tetrahedron Lett. 1990, 31, 209.

(3) Bellassoued, M.; Lensen, N.; Bakasse, M.; Mouelhi, S. J. Org. Chem. 1998, 63, 8785.

(4) Bellassoued, M.; Gaudemar, M. J. Organometal. Chem. 1984, 263, C21.

(5) Bellassoued, M.; Ennigrou, R.; Gil, R.; Lensen, N. Synthetic Commun, 1998, 28, 3955.

(6) Bellassoued, M.; Dubois, J. E.; Bertounesque, E. Synthetic Commun, 1987, 17, 1181.

(7) Bellassoued, M.; Ennigrou, R.; Gaudemar, M. J. Organometal. Chem. 1988, 338, 149.

(8) Bellassoued, M.; Majidi, A. Tetrahedron Lett. 1991, 32, 7253.

CO2SiMe3Me3Si

OSiMe3

OSiMe3SiMe3

Me3Si

OSiMe3

OSiMe3CH2-CO2SiMe3

33101 33105 33112 33111

OSiMe3

OSiMe3

Me3Si

OSiMe3

OSiMe3

OCO2H

++CHOO O

Queen Substance of Honeybee

New organosilicon reagentsBis(trimethylsilyl)ketene Acetals:

Versatile Organosilicon Reagents for Aldolisation Reactions.

Request your copy of the Review from Prof. Bel lassoued of

Bis(Trimethylsilyl)Ketene Acetals: A document with a lot of applications,references and many tables of results, complete with the comprehensive list of

these organosilicon reagents available from stock at Acros Organics!

Moncef Bellassouedand Jrme Grugier


6/20

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8/20Acros Organics Acta 9 - Spring 20026

J. Meijer, A.H. Hogtand B. Fischer Akzo Nobel Polymer Chemicals Laboratory Deventer

Zutphenseweg 10, PO Box 10, 7400 AA Deventer, The Netherlands.

Introduction

Radicals can be used as synthetic intermediates inreactions which are often difficult to accomplishby other means and which can selectively occurunder very mild conditions. The protection of func-tional groups, often essential for synthetic sequencesof ionic reactions, is mostly not required for radicalreactions.1

Organic peroxides are a very versatile source of radi-cals that are formed after the thermally induced

homolysis of the peroxide bond. The major radical-molecule reactions are additions and SH2 reactions,e.g. H-abstraction, atom transfer, unimolecular reac-tions, e.g. decarboxylation, -scission and rearrange-ments, e.g. 1,5-H-abstraction.2 In synthesis reactions,undesired radical-radical reactions such as radicalcombination and disproportionation can be avoidedby proper choice of the type of peroxide and reactionconditions. Another major application of organic per-oxides in syntheses is oxidation, which is a non-radi-cal reaction.3

Oxidation reactions withorganic peroxides

Peroxyacids are mostly used for the epoxidation of unsaturated com-pounds. Most important are the Baeyer-Villiger reaction of carbonylcompounds, oxidation of nitrogen and sulfur compounds3 (see Fig. 3).It is generally accepted that such oxidations are non-radical reactions.

Radical reactions withorganic peroxides

Through homolytic scission organic peroxides primarily generateoxy-radicals: alkoxy-, acyloxy- and/or oxycarbonyloxy-radicals.4

Oxy-radicals can also be generated from peroxyesters, diacylperox-ides and hydroperoxides by redox systems.5 (see Fig. 4).

An important reaction of alkoxy-radicals is -scission, and of acyloxy-radicals decarboxylation, both reactions resulting in the formation ofcarbon-radicals. In contrast, alkoxycarbonyloxy-radicals do not showdecarboxylation.4 (see Fig. 5).

Organic Peroxides in Radical Synthesis Reactions

O

O

O HRO

BAEYER-VILLIGER

R3N

R2S

R2S(O)n=1,2

R3N(O)

R1C(O)R 2

R1C(O)OR 2

EPOXIDATIONPEROXY ACID

Figure 3. Oxidation via peroxy-compounds.

O

O

HO

OO

O

OO

OO

OOO

O

OO

O

R1OOR2

C14H29

C16H33

*

**

* *

*

**DTBP

DTAP DCP

BPO

CPDC

MPDC TBCPDC

BPIC

Figure 4.

Generation of oxy-radicals via peroxy-compounds.

H

R1OOR2

*

**

* *

*

** DTBP

DTAP TBPIB

TBPP

BPO

LPO BTMHP

TBPEH

CH3

C2H5

C11H23

Figure 5.

Generation of carbon-radicals via peroxy-compounds.


9/20

In the presence of a substrate, oxy-radicals (R-H) generate substrate-radicals which may undergo combination reactions, addition reac-tions to unsaturated compounds or atom-transfer reactions. Examplesof such reactions in practical applications are (see Fig. 6): combina-tion of phenylisopropyl-radicals to 2,3-dimethyl-2,3-diphenylbutane,applied as flame-retardant synergist,6 addition of methylphosphorousmono-isobutyl ester to vinylacetic acid ethylester, used in the synthe-sis of the glufosinate herbicide,7 and atom transfer of bromine toa substituted tolyl-radical, yielding a flame retardant.8 In addition,oxy-radicals can be used for the racemization of optically activechrysanthemic acid or its ester used for the synthesis of pyrethrineinsecticides.9

Oxy-radicals can add to unsaturated compounds. They may alsoundergo competitive reactions such as -scission in case of alkoxy-radicals, and decarboxylation in case of acyloxy-radicals. The formedcarbon-radicals will in most cases also add to the unsaturated com-pounds.4,10

Concluding remarks

There are several important parameters for the choice of a peroxidefor use in chemical syntheses. The physical and chemical stabilityaffects the storage and handling properties, the temperature-depen-dent rate of decomposition determines the reactivity at the processconditions. The radicals formed after decomposition must be efficientfor the desired radical reaction. Peroxides may also be selected forspecific rearrangements or specific coupling reactions, which can

introduce functional groups into substrates. Decomposition productsof the peroxides have to be taken in account during the purificationprocess.

Organic peroxides are well established synthetic agents in the manu-facture of many pharmaceutical intermediates, herbicides, insecticidesand various other fine chemicals. Organic peroxides offer opportuni-ties to reduce the number of reaction steps in synthetic routes apply-ing classical synthetic procedures. Moreover, introduction of function-al groups can be achieved by using special organic peroxides. In manycases these reactions are unprecedented in non-radical chemistry.

Organic peroxides combine a number of interesting features for theapplication in organic synthesis:

High purity Good solubility on most organic systems, enabling homogeneous

reaction conditions Well defined and temperature controlled reactivity High efficiency Favorable cost/performance ratio


Organic Peroxides inRadical Synthesis ReactionsJ. Meijer, A.H. Hogt and B. Fischer

Akzo Nobel Polymer Chemicals Laboratory DeventerZutphenseweg 10, PO Box 10, 7400 AA Deventer, The Netherlands.

R H

O P

O

O

O

R1O OR 2* *

R1OH + HOR 2

*RR-X + Y *

ATOM TRANSFER

Br

H

HX

R1OOR2

R-H

ADDITION

ABSTRACTION

[Meiji Saika Kaisha, 1982]

[Tosoh, 1999]

R-R

COMBINATION

[Regitz and Giese, 1989-a]

X-Y2x

Figure 6. Reactions of oxy-radicals with substrates R-H.

Abbreviations

Code Chemical name* CAS nr.

BPIC Tert-butyl peroxy isopropylcarbonate (Trigonox BPIC) 2372-21-6BPO Dibenzoyl peroxide (Lucidol, Cadet) 94-36-0BTMHP Bis(3,5,5-trimethylhexanoyl) peroxide (Trigonox 36) 3851-87-4CPDC Dicetyl peroxydicarbonate (Perkadox 24) 26322-14-5DCP Dicumyl peroxide (Perkadox BC) 80-43-3DTAP Di-tert-amyl peroxide (Trigonox 201) 10508-09-5DTBP Di-tert-butyl peroxide (Trigonox B) 110-05-4EHP Bis(2-ethylhexyl) peroxydicarbonate (Trigonox EHP) 16111-62-9LPO Dilauroyl peroxide (Laurox) 105-74-8MPDC Dimyristyl peroxydicarbonate (Perkadox 26) 53220-22-7TBCPDC Bis(4-tert-butylcyclohexyl) peroxydicarbonate (Perkadox 16) 15520-11-3

TBHP Tert-butyl hydroperoxide (Trigonox A) 75-91-2TBPB Tert-butyl peroxybenzoate (Trigonox C) 614-45-9TBPEH Tert-butyl peroxy-2-ethylhexanoate (Trigonox 21) 3006-82-4TBPIB Tert-butyl peroxyisobutanoate (Trigonox 41) 109-13-7TBPP Tert-butylperoxy pivalate (Trigonox 25) 927-07-1

* Cadet, Laurox, Lucidol, Perkadox, Trigonox are tradenames of Akzo Nobel.


10/20

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References1 Curran, D.P., Porter, N.A., Giese, B., Stereochemistry of Radical Reactions, VCH

Verlagsgesellschaft, Weinheim, Germany (1996), pp. 1-22.

2 Ingold, K.U., Rate constants for free radicals in solution, in: Kochi, J.K. (Ed.), FreeRadicals, Vol. I, Wiley, New York (1973), Chapter 11, pp. 37-112.

3 Rao, A.S. and Mohan, H.R., in: Burke, S.D. and Danheiser, R.L., Handbook ofReagents for Organic Synthesis, Oxidizing and Reducing Agents, Wiley,Chichester, UK (1999), pp. 84-89.

4 Kochi, J.K., Oxygen radicals, in: Kochi, J.K. (Ed.), Free Radicals, Vol. II, Wiley, NewYork (1973), Chapter 23, pp. 665-710 (a).

5 Kochi, J.K, Oxidation-reduction reactions of free radicals and metal complexes, in:Kochi, J.K. (Ed.), Free Radicals, Vol. I, Wiley, NY (1973), Chapter 11, pp. 591-684 (b).

6 Regitz, M. and Giese, B. (Eds.), C-Radikale Band E19a, Methoden der OrganischenChemie(Houben-Weyl), Thieme Verlag, Stuttgart (1989), pp. 547-548 (a).

7 Meiji Seka Kaisha, Ltd, European patent EP18415 (1982).

8 Tosoh Corp., Japanese patent JP 11130708 (1999).

9 Sumitomo Chemical Company, Ltd, European patent EP282221 (1992).

10 Regitz, M. and Giese, B. (Eds.), C-Radikale Band E19a, Methoden der OrganischenChemie(Houben-Weyl), Thieme Verlag, Stuttgart (1989), pp. 31-40 (b).

For the full review article by Meijer, Hogt and Fischer cover-

ing this as well as discussions on reactivity of organic perox-

ides and functionalization reactions with organic peroxides

you can request your free copy of Acros Organics Review 6.


34988 . . . . . . . . . . . . . . . . . . . . . . . . . .Dicumyl peroxide

34993 . . . . . . . . . . . . . . . . . . . . . . .Di-tert-butyl peroxide

21178 . . . . . . . . . . . . . . . . . . . . . . . . .Dibenzoyl peroxide

36131 . . . . . . . . . . . . .1,1-Di(tert-butylperoxy)cyclohexane

34996 . . . . . . . . . . . . . . . . . . . . . . .Cumyl hydroperoxide

34974 . . . . . . . . . . . . . . . . . . . . . . . . . . .Lauroyl peroxide

34994 . . .3,6,9-Triethyl-3,6,9-trimethyl-1,4,7-triperoxonane

34977 . .1,1--Di-(tert-Butylperoxy)-3,3,5-trimethylcyclohexane

34983 . . . . . . . . . . . . . . . . .2,2-Di(tert-butylperoxy)butane

34986 . . . . . . . . . . . . . . . . . . . . . .tert-Butyl peroxyacetate

17014 . . . . . . . . . . . . . . . . . . . .tert-Butyl peroxybenzoate

34985 . . . . . . . . . .tert-Butylperoxy 2-ethylhexyl carbonate

34981 . . . . . .tert-Butyl peroxy-3,5,5-trimethylcyclohexane

34984 . . . . . . . . . . . .tert-Butylperoxy isopropyl carbonate

34989 . . . . . . . . . . . .di(tert-butylperoxyisopropyl)benzene

34991 . . . . . . . . . . . . . . . . . . . . .tert-Butyl cumyl peroxide

34990 . . . . . . .2,5-Dimethyl-2,5-di(tert-butylperoxy)hexane

18034 . . . . . . . . . . . . . . . . . . . . .tert-Butyl hydroperoxide

ORGANIC PEROXIDES FROM ACROS ORGANICS

Event name Location Country Date

Informex New Orleans (LA) USA 26 February - 1 March 2002

ACS National Meeting Orlando (FL) USA 8 - 10 April 2002

Drug Discovery Technology Stuttgart Germany 15 - 18 April 2002

Drug Analysis 2002 Brugge Belgium 21 - 25 April 2002

SECO 39 Saint Jean de Monts France 26 May - 1 June 2002

11th Fechem Conference Barcelona Spain 9 - 12 June 2002Heterocycles in Bio-Organic Chemistry

27th European Peptide Symposium Sorrento Italy 31 August - 6 September 2002

14th International Symposium on Chiralty Hamburg Germany 8 - 12 September 2002

Organic Peroxides inRadical Synthesis ReactionsJ. Meijer, A.H. Hogt and B. Fischer

Akzo Nobel Polymer Chemicals Laboratory DeventerZutphenseweg 10, PO Box 10, 7400 AA Deventer, The Netherlands.


11/20

This report describes two procedures for the synthesis of (S)- and (R)-N-Boc--methylserinal acetonides 1 and 4.The application of both compounds as valuable chiral building blocks in the asymmetric synthesis of-methyl-amino acids 2 and 3 is also reported.


(S)- and (R)-N-Boc-N,O-Isopropylidene--methylserinals

Preparation and Synthetic Applications

ONBoc

CHOO

BocN

OHC RS

H2N

HO2C R

NH2

CO2HR

1 42 3

Introduction

Over the last decade, there has been sustained interest in the develop-ment and use of chiral N-protected--amino aldehydes due to their

wide utility in organic synthesis (1). While the (S)-N-Boc-N,O-isopropy-lidene serinal 5, Garner's aldehyde (2), and its enantiomer 6 are wellknown as chiral building blocks in stereocontrolled organic synthesis,it is only very recently the synthesis of their homologues 1 and 4 havebecome appreciated and their chemistry investigated (scheme 1).

In this context, and taking into account the special role that ,-dialkylamino acids have played in the design of peptides withenhanced properties, we have focused our attention on the stereose-

lective synthesis of a-methylamino acids. Indeed, (S)- and (R)--methyl derivatives 1 and 4 can be regarded as ideal precursors for thesynthesis of quaternary-methylamino acids.

Synthesis

The first synthesis (3) of the homologue of serinal 5, the (S)--methylderivative 1, was achieved on a milligram scale starting from (S)--methylserine and using a similar procedure to that described for thesynthesis of Garner's aldehyde (2).

Furthermore, we described a new and more convenient synthesis pro-cedure for (S)- and (R)--methylserinals 1 and 4 on a gram scale start-

ing from (R)-2-methylglycidol (4). Nevertheless, the best method toachieved these serinals on a multigram scale starts from the Weinrebamide of 2-methyl-2-propenoic acid (5), which is easily obtained fromthe commercially available 2-methyl-2-propenoic acid (6)- and uses astereodivergent synthetic route, that involves a Sharpless asymmetricdihydroxylation reaction (AD) (scheme 2).

The AD reaction of Weinreb amide of 2-methyl-2-propenoic acid inthe presence of AD-mix-a proceeded with excellent e.e. to yield thediol 7. The amide group of diol 7 was converted into the methyl estergroup to obtain the corresponding diol in two steps: basic hydrolysis

with LiOH/MeOH and subsequent esterification with AcCl in MeOH.This diol was transformed into its 2,3-cyclic sulfite 9 with thionyl chlo-ride (scheme 2).

O

NBocRCHO

O

BocNR

OHC RS

1: R = Me5: R = H

4: R = Me6: R = H

Scheme 1 N

OS O

O

CO2Me

OH

N3

MeO2C

S

HO

N3

CO2Me

R

S R

7

4

8

9 10

11 12

1

OSO

O

MeO2C

HOHO

SROH

OH

O

O

N

O

ON

O

O

AD-mix-AD-mix-

2. (Boc)2O, Na2CO33. DMP, BF3Et2O

4. LiAlH45. Swern

1. H2, Pd-C

1. NaN3, DMF

2. chromatography

2. AcCl, MeOH

3. SOCl2, CCl4

1. LiOH

Scheme 2

A. Avenozaa, C. Cativielab,F. Corzanaa, J. M. Peregrinaa,D. Sucunzaa and M. M. Zurbanoa

(b) Departamento de Qumica Orgnica, Instituto de Ciencia de Materialesde Aragn, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain

(a) Departamento de Qumica, Universidad de La Rioja, Grupo de SntesisQumica de la Rioja, UA-CSIC, 26001 Logroo, Spain;


12/20Acros Organics Acta 9 - Spring 200210

Reaction of sulfite 9 with NaN3 in the presence of DMF as a solventgave a mixture of azido esters with a regioselectivity of 20/80 in favourto -azido ester 11. Once separated, -azido ester 11 was readilyhydrogenated in the presence of Pd-C to give the corresponding -amino ester, which was subsequently treated with (Boc)2O in a basicmedium to get the N-Boc amino alcohol. This compound was con-

verted into the corresponding oxazolidine by the use of 2,2-dimethoxypropane (DMP) with BF3Et2O and the required buildingblock (S)--methylserinal 1 was obtained from this oxazolidine in twosteps involving a reduction-oxidation sequence (26% overall yieldfrom olefin Weinreb amide, using 8 steps) (scheme 2). The otherenantiomer, the (R)--methylserinal 4, was obtained using the samestrategy described above and also starting from Weinreb amide of 2-methyl-2-propenoic acid, but changing the chiral catalytic ligand to

AD-mix- in the AD reaction (scheme 2).

Synthetic applications

In order to demonstrate that (S)- and (R)-N-Boc--methylserinal ace-tonides 1 and 4 are valuable chiral building blocks in the enantiose-lective synthesis of-methyl -amino acids, we have recently report-ed their use as starting material in the preparation of enantiomericallypure -substituted alanines by transformation of the aldehyde groupinto ethyl, vinyl or ethynyl groups. In this methodology, the oxazoli-dine ring contributes the amino acid moiety and the stereogenic cen-tre was already created in the starting material.

However, more recently we also explored the fact that this oxazoli-dine ring can behave as an excellent chiral inductor to create anothernew stereogenic centre in the asymmetric Grignard addition reactionsto aldehydes. In this way, the synthetic utility of both -methylserinals1 and 4 as chiral building blocks has been proved in the synthesis ofthe four enantiomerically pure -methyl--phenylserines.

1. Reactivity of aldehyde group without generation of newstereogenic centres

Starting from (S)--mehylserinal 1 and (R)--methylserinal 4, andusing five steps, we obtained both enantiomers of Iva 19 and 20 withan overall yield of 61% (scheme 3) (7).

Olefination of aldehyde group was carried out under salt-free Wittigconditions using methyltriphenylphosphonium bromide and potassi-um bis(trimethylsilyl)amide (KHMDS) as base, obtaining olefin 13,

which was hydrogenated using Pd-C to give oxazolidine 15. Thecleavage of the acetonide moiety of 15 was achieved using Sc(OTf)3(10 mol%) to obtain compound 17, which was converted into (R)-Iva19 as follows. It was oxidized by treatment with Jones reagent to givethe corresponding protected amino acid, which was then subjected tohydrolysis using a mixture of concentrated HCl and THF. Liberation ofthe amino acid from its hydrochloride salt was then achieved by treat-ing with propylene oxide in ethanol to furnish (R)-Iva 19 in high yield.

The enantiomer of (R)-Iva: (S)-Iva 20 was obtained using the samestrategy but starting from 4 (scheme 3).

We have also developed a methodology that offers a straightforwardroute to the synthesis of ,-unsaturated -methyl -amino acids.Indeed, we have achieved the synthesis of four interesting quaternary-amino acids in enantiomerically pure form: (R)- and (S)-vinylala-

nines 23 and 24 and (R)- and (S)-ethynylalanines 29 and 30 (7).Starting from olefin 13, we carried out acid hydrolysis, obtaining thecleavage of the acetonide moiety and the hydrolysis of the N-Boc. Thecorresponding aminoalcohol hydrochloride was then protected withBoc2O to give 21. The transformation of this compound into the qua-ternary amino acid (R)--vinylalanine 23 was achieved according tothe protocol described above to transform alcohol 17 into amino acid19. The enantiomer (S)--vinylalanine 24 was obtained using thesame strategy but starting from olefin 14 (scheme 4).

O

NBoc

O

BocN

ONBoc

EtO

BocN

Et

EtHOCH 2

BocHN

Et CH2OH

NHBoc

R S

R S

R S

Ph 3PCH3Br,KHMDS , THF

EtHO2C

H2N

Et CO2H

NH2

R S

13

17

H2/Pd-C,AcOEt

Sc(TfO)3CH3CN/H2O

15

1. Jones oxidation2. HCl (conc.)/THF

3. Propyleneoxide, EtOH

19

4

14

18

16

20

1

Scheme 3



A. Avenozaa, C. Cativielab, F. Corzanaa, J. M. Peregrinaa, D. Sucunzaa and M. M. Zurbanoa

(a) Universidad de La Rioja, Grupo de Sntesis Qumica de la Rioja, UA-CSIC, 26001 Logroo, Spain;(b) Instituto de Ciencia de Materiales de Aragn, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain


13/20

The synthesis of (R)- and (S)--ethynylalanines 29 and 30 also startsfrom (S)- and (R)--methylserinals 1 and 4, respectively, and involvesseven steps with an overall yield of 32% (scheme 5). The aldehyde-to-acetylene conversion was undertaken in two steps using a dibro-movinyl intermediate (the Corey-Fuchs strategy). Methylserinals 1 and4 were converted into the corresponding alkynes 27 and 28, using the

vinyl intermediates 25 and 26 (scheme 5).

The conversion of compounds 27 and 28 into (R)- and (S)-ethynylala-nines 29 and 30 was achieved in the same way described above forthe preparation of amino acid 19 from alcohol 17 (scheme 5).

2. Reactivity of aldehyde group with generation of a newstereogenic centre

In order to demonstrate the synthetic utility of both -methylserinals

1 and 4 as chiral building blocks in asymmetric synthesis with gener-ation of a new stereogenic centre, we tried the reaction of thesealdehydes with phenyl nucleophiles under different conditions(scheme 6) (8).

In general, the results obtained indicate that the model proposed toexplain the diastereoselectivity observed in the nucleophile additionsis similar to that described for Garner aldehyde (9). The onlydifference observed is a significant increase of diastereoselectivity in

favor to 31.Starting from enantiomerically pure 31, which was obtained by theattack of PhMgBr on -methylserinal 1, we synthesised (2R,3R)--methyl--phenylserine 35 with an overall yield of 54% (8), using foursteps: intramolecular cyclization in compound 31, promoted by theattack of the alkoxide ion on the carbonylic carbon of the Boc groupto give the bicyclic compound 33, selective deprotection of the ace-tonide moiety of 33 by the action of BF32AcOH to give the corre-sponding oxazolidinone, subsequent Jones oxidation and acidhydrolysis. Liberation of the amino acid 35 from its hydrochloride salt

was achieved by the propylene oxide method. The diastereoisomer

(2R,3S)--methyl--phenylserine 36 was also obtained (8) startingfrom 31 but now by a different type of intramolecular cyclization thatuses triflic anhydride to give the bicyclic compound 34, with inversionof configuration at the benzylic carbon.

HO2C

H2N

CO2H

NH2

R S

HOCH 2

BocHN

R S

2. Na2CO3, Boc2O,1. HCl

H2O-THF

CH2OH

NHBoc

13

21

23

14

22

24

1. Jones oxidation2. HCl (conc.)/THF3. Propylene

oxide, EtOH

Scheme 4

O

NBoc

CHOS

ONBoc

SPh

H OH

R

O

NBoc

SPh

HO H

S1

31

32

+

phenylnucleophile

Scheme 6

Scheme 5


HOCH 2

BocHN

CH2OH

NHBoc

R S

R S

CO2H

NH2

R S

ONBoc

Br Br

OBocN

BrBr

HO2C

H2N

25

27

1. Jones oxidation2. HCl (conc.)/THF3. Propylene

oxide, EtOH

29

26

28

30

1. BuLi, THF, -78 C2. HCl.3. Na2CO3, Boc2O,

H2O-THF

CH Br3,tBuOK,

PP h3, PhMe

41






14/20

Using the same strategy explained to prepare amino acid 35 from 33,the amino acid 36 was obtained from compound 34 in a 43% yield(scheme 7) (8).

The enantiomers (2S,3S)- and (2S,3R)--methyl--phenylserines 40

and 41 were obtained using the same strategy described above inscheme 7, but starting from (R)--methylserinal 4 (scheme 8) (8).

Conclusion

We report a large scale and stereodivergent synthesis of the (S)- and(R)--methylserinals 1 and 4, starting from commercially available(R)-2-methylglycidol 7. These compounds have proved to be valuablestarting materials in a new approach to the synthesis of different qua-ternary-methylamino acids.

We have also developed the asymmetric synthesis of the fourstereoisomers of-methyl--phenylserines, via the highly diastereos-

elective Grignard addition reactions of PhMgBr on the chiral aldehy-des 1 and 4. Indeed, the oxazolidine ring of 1 and 4 has been exploit-ed as the precursor of the amino acid moiety and, moreover, as chiralauxiliary to create another new stereogenic centre in the asymmetricreactions.

References(1) Jurczak, J.; Golebiowski, A. Chem. Rev. 1989, 89, 149.

(2) Garner, P.; Park, J. M. Org. Synth. 1992, 70, 18.

(3) Alas, M.; Cativiela, C.; Daz-de-Villegas, M. D.; Glvez, J. A.; Lapea, Y.Tetrahedron1998, 54, 14963.

(4) Avenoza, A.; Cativiela, C.; Corzana, F.; Peregrina, J. M.; Zurbano, M. M. J. Org.Chem. 1999, 64, 8220.

(5) Avenoza, A.; Cativiela, C.; Corzana, F.; Peregrina, J. M.; Sucunza, D.; Zurbano, M.M. Tetrahedron: Asymmetry2001, 12, 949.

(6) Nahm, S.; Weinreb, S. M. Tetrahedron Lett. 1981, 22, 3815.

(7) Avenoza, A.; Cativiela, C.; Peregrina, J. M.; Sucunza, D.; Zurbano, M. M.

Tetrahedron: Asymmetry1999, 10, 4653.(8) Avenoza, A.; Cativiela, C.; Corzana, F.; Peregrina, J. M.; Zurbano, M. M.

Tetrahedron: Asymmetry2000, 11, 2195.

(9) Williams, L.; Zhang, Z.; Shao, F.; Carroll, P. J.; Joulli, M. M. Tetrahedron1996, 52,11673.


HOOC

H2N

ROH

Ph H

R

Tf2O

O

N

S

O

PhH

O

R O

N

S

O

HPh

O

S

HOOC

H2N

R

OH

H Ph

S

NaH, DMF

1. BF32AcOH2. Jones oxidation3. HCl (conc.)/THF4. Propylene

oxide, EtOH

35

33 34

36

31Scheme 7

HOOC

H2N

SOH

H Ph

S

Tf2O

ON

R

O

HPh

O

SO

NR

O

PhH

O

R

HOOC

H2N

SOH

Ph H

R

NaH, DMF

O

NBoc

R

PhMgBr

Ph

HO H

S

1. BF32AcOH2. Jones oxidation3. HCl (conc.)/THF4. Propylene

oxide, EtOH

40

38 39

41

37

4Scheme 8

16831 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Methacrylic acid (2-Methyl-2-propionic acid)

15127 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Acetyl Chloride, 98%

21947 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Acetyl Chloride, p.a.

18977 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Di-tert-butyl dicarbonate, 97% [(Boc)2O]19467 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Di-tert-butyl dicarbonate, 99% [(Boc)2O]

15695 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Methyltriphenylphosphonium bromide, 98%

11563 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2,2-Dimethoxypropane, 98% [DMP]

36389 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Scandium (III) trifluoromethanesulfonate [Sc(OTf)3]

ADDITIONAL CYCLOPROPANE CARBOXYLIC ACIDS AND DERIVATIVES

(S)- and (R)-N-Boc-N,O-Isopropylidene-a-methylserinals





15/20

What is green chemistry all about?

Green chemistry is all about reducing the number and amount ofharmful chemicals that are used and/or generated in research andindustry, by developing harmless, green chemicals and/or process-es. This new field is all about minimising the amount of waste till the

point where you end up with no waste at all.

Where does green chemistry stand now?

The green chemistry principle is still very much in its infancy, it hasnot yet penetrated the mainstream chemical lab in research or indus-try and is not yet part of the curriculum in the education of youngchemists.

However, there are good omens today that green chemistry is startingto pick up speed. For instance, the Royal Society of Chemistry in theU.K. now has a journal that is dedicated to this issue it is called quite

aptly Green Chemistry. The April 2002 issue will be devoted to ionicliquids, for example. In addition, papers on the subject are being wellcited, which is a good meter for the interest in the subject.

What do you think the influenceof green chemistry will be onorganic chemistry?

Well, I am pretty sure that it will revolutionise the way we are doingchemistry now. It is a new vision that creates lots of new challenges.For instance, it is much more difficult to selectively oxidise an organ-

ic substrate with O2, but it is possible, although it requires newapproaches.

Of course, it will take time. Some look at green chemistry as a veryexpensive approach, which is quite a narrow way to view the subject.Indeed, the opposite should be true. There is much more to it thanthat. If I look at the reactions I get whenever I give a lecture on greenchemistry, it gives me a feeling that we will see the interest in this mat-ter grow rapidly in the near future.

How did you get involved withgreen chemistry?

The whole concept of green chemistry comes from Prof. Paul T.Anastas of the White House Office of Science & Technology Policy(OSTP). He wrote all the key textbooks on the subject and defined theterms we currently use. Anastas is also the one who defined the 12basic principles of green chemistry. We owe him a lot.

Another person that played an important role in the development ofthis subject is certainly Professor Roger Sheldon. He is currently the

chairman of the editorial board of the Green Chemistry journal.

What does QUILL stand for?

QUILL is an acronym for the Queens University Ionic LiquidsLaboratory. It is an industry-university collaborative research centrefocusing on ionic liquids. It consists of a consortium of 20 industrialcompanies to support research on ionic liquids.

INTERVIEWwith Professor Ken Seddon

on Green Chemistry / Ionic Liquids

For a free copy of the new

Ionic Liquids Handbook, fill inthe fax form on page 16 orthe registration form on the

Internet: www.acros.com


16/20

Solid Phase Synthesis

The use of polymer supports in organic synthesis is

becoming well established as demonstrated by the

massive increase in the number of publications

referring to it.The key reported advantages

for solid-phase synthesis being faster and

simplified procedures for the genera-

tion of a large number of com-

pounds (use of automation/ ease

of purification of intermedi-

ates and products/ use of

excess starting material).

At Acros Organics, we

understand that for a

solid phase synthesis

procedure to fulfill

i t s a d v a n t a g e o u s

promises, it is crucial

to select the correct

resin matrix and link-er(s) for the reaction

under consideration. A

selection of polystyrene

and TentaGel resins for

solid phase synthesis with

a broad variety of linker

groups and narrow-range

loading capacities has been recent-

ly introduced to our stock.

Solution Phase Synthesis

Solution phase synthesis, where a reactive, functional group

specific scavenger, a reagent, a ligand, or catalyst is attached to

a polymer support, has been a fast growing area of synthesis.

This methodology takes advantage of new developments with-

in the field of solid phase synthesis and adapts them to the

existing vast repertoire of chemical reactions.A wide range of

resins for solution-phase synthesis have been introduced to

Acros Organics to respond to the needs of the organic

chemist adopting solution-phase strategies in his synthesis.

NEW RESINS FROM ACROS ORGANICSFOR SOLID SUPPORTED CHEMISTRY

A wide range of resins for Solid Phase and Solution

Phase Synthesis have been introduced by Acros

Organics.Visit www.acros.com for the latest additions.


17/20Acros Organics Acta 9 - Spring 2002 15

N CO2H.H2NBn

OH

Boc

36201

OH

36235

MeO2C NHBoc

OH36233

NHBocMeO2C

N CO2Me

OH

Boc

36200

NH

O

OO

36220

MeO2CCO2H

36208

CO2HH2N

F

3630136217

OH

NH2

CO2HFmocHN

Me

36148

We are pleased to announce that research quantities of theChiroTech product range are now available exclusively through

Acros Organics. These products can be ordered through your localAcros Organics distributor or via the internet at www.acros.com.

Through this collaboration with ChiroTech, Acros Organics is able toprovide an unmatched product offering and service level to assist youin your drug design and discovery research.

Over 182 products have been introduced to our product range, includ-ing high added value building blocks, intermediates, and advancedintermediates such as multi-functional single diastereomer scaffoldssuitable for elaboration into potential drug-like compounds.

All compounds are offered with the assurance of robust scaleableprocesses to make larger quantities of material available at minimal leadtimes as your hit compound makes it from discovery to development.

A sample of NEW functionalized cyclopentane and piperidine scaffolds

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For enquiries regarding

larger quantities of ChiroTechproducts, please contactthe ChiroTech SalesAdministrator on+44 1223 728026, ore-mail [email protected]

NEW

NEW

H

N N

O O

Co

+ +

32995

H H

N N

O O

Co

+ +

32996

References

1 Furrow, M. E.; Schaus, S. E.; Jacobsen, E. N. J. Org. Chem. 1998, 63, 6776.

2 Tokunaga, M.; Larrow, J. F.; Kakiuchi, F.; Jacobsen, E. N. Science1997, 277, 936.

3 Jacobsen, E. N. Acc. Chem. Res. 2000, 33, 421.

NEW catalysts for Hydrolytic KineticResolution: (R, R) and (S, S)-(Salen)Co(III) acetate 1

Complexes 1 catalyze the kinetic resolution of racemic, terminal

epoxides. This is a highly desirable reaction leading to the formationof a chiral diol and the unreacted epoxide enantiomer.1,2,3 The Co(III) acetate complexes are generated in situ from the correspondingsalen Co (II) complexes 32995 and 32996 by reaction with 1-2 eq. ofacetic acid and exposure to air.

N N

O O

Co

OAc

+ +

(R,R) -1

H2O

OR R

O R OH

OH

+

ChiroTechisaregis

teredtrademarkofChirotechTechnologyLimited.

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18/20

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Substrates Neurochemicals Drug discovery Ionic liquids handbook Chirals

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(free subscription)

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New N7: A Novel Catalyst

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N......

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Fax this form

for additional

information :

Catalogue Specialty CatalogueCatalogues on CD-ROM

(Europe & Asia) (USA only)

Solid Phase Synthesis

You will find

a list of all

available

Reviews on

the back of the

inside cover.


19/20

A selection of peptide grade reagents, formulations, and solvents

has been recently added to our product range and are listed below.

ReadyMix products are peptide grade reagents and solvents in themost popular formulations used by the peptide synthesis chemists.

They are now available from Acros Organics, in ready to use solutionsor in kits containing pre-weighed amounts of activating agents and

solvents to be mixed immediately prior to use.

Product Nr. Pack. Name Specifications

35480 0025 2.5L Dichloromethane (DCM), peptide synthesis grade. H2O (KF) max 0.005%. Residue on evaporation max 0.0005%.Free amines (Kaiser) max 0.0001%.

35483 0025 2.5L N,N-Dimethylformamide (DMF), peptide synthesis grade. Acidity max 0.001%. Water (KF) max 0.02%. Free amines (Kaiser)max 0.001%. Residue on evaporation max 0.001%. Formaldehydemax 0.002%.

35484 0025 2.5L Methyl sulfoxide (DMSO), peptide synthesis grade. Water (KF) max 0.005%. Residue on evaporation max 0.001%.Peroxides (as H2O2) max 0.001%. Free amines (Kaiser) not detected.

35486 1000 100ml 1,1,1,3,3,3- Hexafluoro-2-isopropanol (HFIPA), Water (KF) max 0.02%. Free amines (Kaiser) not detected.peptide synthesis grade. Residue on evaporation max 0.0005%.

35489 0025 2.5L 1-Methyl-2-pyrrolidone, special automatic peptide Water (KF) max 0.03%. Residue on evaporation max 0.002%.synthesizer grade. Free amines (Kaiser) max 0.001%.

UV absorbance: 285nm max 0.065 AU.300nm max 0.035 AU.325nm max 0.010 AU.350nm max 0.005 AU.

35490 0025 2.5L 1-Methyl-2-pyrrolidone (NMP), peptide synthesis grade. Water (KF) max 0.03%. Residue on evaporation max 0.002%.Free amines (Kaiser) max 0.001%.

35487 1000 100ml 1,1,1,3,3,3- Hexafluoro-2-isopropanol, 10% in Water (KF) max 0.01%.dichloromethane, ReadyMix, peptide synthesis grade.

35491 0010 1L Piperidine, 20% in N-Methyl-2-pyrrolidone, Prepared from peptide grade materials.ReadyMix, peptide synthesis grade.

35481 1000 100ml N,N'-Dicyclohexylcarbodiimide (DCC) Prepared from peptide grade materia ls .0.1M solution in Dichloromethane,ReadyMix, peptide synthesis grade.

35482 2000 200ml N,N'-Dicyclohexylcarbodiimide (DCC) Prepared from peptide grade materia ls .1.0M in N-Methyl-2-pyrrolidone,ReadyMix, peptide synthesis grade.

35485 2000 200ml HBTU 0.1M in (HOBT 0.45M in DMF) 1:1, 3 Bottles kit of pure HBTU, HOBT and DMF to be mixedReadyMix, peptide synthesis grade. prior to use to give 3.79%HBTU in [6.08%HOBT in DMF].

35488 2000 200ml HOBT 0.5M in N,N-dimethylformamide, 2 Bottles kit of pure HOBT and DMF to be mixed prior

ReadyMix, peptide synthesis grade. to use to give 6.76% HOBT in DMF.

Peptide Grade Reagents, Solvents and Formulations

Contact us for special prices and availability

Most Peptide grade solvents are available in 1l and 2.5 l bottles

Ready Mix kits: convenient pack sizes

no tedious preparation

prepared with high quality reagents

complete range of most popular mixes.


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ACROS ORGANICSGeel West Zone 2

Janssen Pharmaceuticalaan 3a


Tel.: +32(0)14/57.52.11

Fax: +32(0)14/59.34.34

ACROS ORGANICS USA500 American Road,

Morris Plains, NJ 07950Tel.: 1-800-766-7000

Fax: 1-800-926-1166

Internet: http://www.fishersci.com(US orders only)

ACROS ORGANICS on-line

ACROS ORGANICSGeel West Zone 2

Janssen Pharmaceuticalaan 3a


Tel.: +32(0)14/57.52.11

Fax: +32(0)14/59.34.34

ACROS ORGANICS USA500 American Road,

Morris Plains, NJ 07950Tel.: 1-800-766-7000

Fax: 1-800-926-1166

Internet: http://www.fishersci.com(US orders only)

ACROS ORGANICS on-line

For more information, please contact your local dealer

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