will (group meeting)
Post on 24-Jan-2017
31 Views
Preview:
TRANSCRIPT
Chiral Phosphine-Catalyzed Asymmetric Intermolecular -Addition of Oxygen Nucleophiles
William ReichardSURF 2014October 18, 2014Chiral Phosphine-Catalyzed Asymmetric Intermolecular -Addition of Oxygen Nucleophiles
Oxygen Nucleophiles in Intermolecular -Addition ReactionsAlcohol Nucleophiles
Carboxylate/Carboxylic Acid Nucleophiles
Trost, B. M. J. Am. Chem. Soc. 1994, 116, 10819.Lu, X. Synlett 1995, 645.
Alvarez-Ibarra, C. Tetrahedron Lett. 1999, 40, 8465.
2
Oxygen Nucleophiles in Intramolecular Asymmetric -Addition Reactions
Chung, Y. K. Angew. Chem., Int. Ed. 2009, 48, 2225.
-Addition, -Addition, and Diene Formation-addition
-addition diene formation
4
Other Strategies For Synthesizing -Hydroxy-Unsaturated Carbonyl Compounds Generating the Stereocenter to a Carbonyl
Brusse Tetrahedron 2000, 56, 2491.Zhong, Org. Lett. 2004, 6, 1637.Krawczyk Synthesis 2008, 20, 3299.
5
Other Strategies For Synthesizing -Hydroxy-Unsaturated Carbonyl Compounds Asymmetric Functionalization of ,-Unsaturated Carbonyl Compounds
Tiecco, Chem. Eur. J. 2002, 8, 1118.Bruckner, Synlett 2001, 718.
6
Other Strategies For Synthesizing -Hydroxy-Unsaturated Carbonyl Compounds Enantioselective Nucleophilic Additions to Aldehydes
Trost, Chem. Eur. J. 2012, 18, 16498.Wang, Org. Lett. 2007, 9, 2329.
7
Advantages of phosphene -addition over other strategiesMakes use of few and easily synthesized reagents, while some other strategies make use of numerous reagents, some of which might not be easily accessible. Simple one step reactionCan simply set up the reaction and set aside to react overnight.Multi step reactions require more care and attentionRelatively mild conditionsReaction set up in nitrogen atmosphere, then left to react at room temperature.Some other strategies must be carried out in harsher conditions.
8
Synthesis
Aromatic Heterocycle-Substituted AlkynoatesYield: 66%Yield:77%Yield:11%Product decomposed on silica, crude product was used in next step
9
Synthesis
Aromatic Heterocycle-Substituted AlkynoatesYield:86%
Yield:69%Yield:92%Yield:87%Tosyl protecting group added in order to prevent decomposition
10
Synthesis
Aromatic Heterocycle Substituted Alkynoates
Yield:31%Yield:65%Yield:89%Yield:7% +crude product
11
Synthesis
Varying the EWG of the Alkynoate
Yield:67%No product formation observed for many similar reactions
Yield:74%Yield:19%Changed synthetic route
12
Oxygen -Addition
Aromatic Heterocycle-Substituted Alkynoates
Yield: 69%ee: 94%Yield:
top related