the nazarov cyclization -...
TRANSCRIPT
The Nazarov Cyclization Michael Moskowitz
Contents
• Background • Mechanism • Stereochemistry • Polarized π-‐system cycliza;ons • Interrupted Nazarov cycliza;ons • Masked Nazarov cycliza;ons/cascades
1
Background
• Ivan Nazarov (1906-‐1957)
• Chemist at Leningrad State University (St. Petersburg State University)
• Discovered Nazarov cycliza;on in 1941
Nazarov, I.N.; Zaretskaya, I.I. (1941), Izv. Akad. Nauk. SSSR, Ser. Khim: 211–224
2
Overview
• Stereoselec;vely form cyclopentenones from divinyl ketones • Tolerant of a wide range of func;onal groups • Catalyzed by both Lewis and Brønsted Acids
3 Wenz, D. R.; Read de Alaniz, J. European J. Org. Chem. 2015 (1), 23–37
LAO O
Mechanism
4
LAO LA OO O LA
1 2 3 4
Wenz, D. R.; Read de Alaniz, J. European J. Org. Chem. 2015 (1), 23–37
Stereochemistry
5
O
R2 R3
R1 R5
R4
O
R2 R3
R1 R5
R4
LA O LA
R2 R3 HR4
R1 R5
O
R2 R3
R1 R5
R4
5 6 7 8
W. T. Spencer III, T. Vaidya, A. J. Frontier, Eur. J. Org. Chem. 2013, 3621– 3633
Electrocyclization Review
6
O LA
University of Michigan. Nazarov Cycliza;on Reac;on: FMO Treatment h_p://www.umich.edu/~chemh215/W10HTML/SSG4/ssg4/Nazarov.html.
Polarized π-System
7
OEW ED
R1 R2
O
EW ED
R1 R2
LA
9 10
W. He, X. Sun, A. J. Frontier, J. Am. Chem. Soc. 2003, 125, 14278–14279
Interrupted Nazarov Cyclization
8 T. N. Grant, C. J. Rieder, F. G. West, Chem. Commun. 2009, 5676–5688
O
R2
R1 R4
R3
R1 R4
R2 R3
O LA
Nu R1 R4
R2 R3
ONu
11 12 13
Masked Pentadienyl Cation
• More complex systems can pass though the pentadienyl ca;on intermediate
• Featured in many diverse cascade reac;ons
9
Masked Pentadienyl Cation
10
O
R
AuCl3/AgSbF6
Toluene, 40-96%
OH
R
O
R
3+Au hetero-enyne metathesis
O
R
Au3+
14 15
16 17
T. Jin, Y. Yamamoto, Org. Lett. 2008, 10, 3137–3139
More Cascade Reactions
11
C
RR
cat. AuClPPh3/AgSbF6
DCM, 0 °CR= H (61%)R=Me (73%)
C
R
AuL
R
AuL
G. Y. Lin, C. Y. Yang, R. S. Liu, J. Org. Chem. 2007, 72, 6753–6757.
Intermolecular Cascades
12
N
O
OR1R2
R3C
Li O χc
H HCR1R2
OR3 O χc
H H
H+
-χc
O
HO
R1 R2R3
M. A. Tius, Acc. Chem. Res. 2003, 36, 284–290.
My work!
13
OH
OO
O
O
TMSOTf, DCM O
O OO
OTf
O
OO
PMP
O
O
O
HO
O
OH
O
N
References
• 1. Wenz, D. R.; Read de Alaniz, J. European J. Org. Chem. 2015, 2015 (1), 23–37
• 2. W. T. Spencer III, T. Vaidya, A. J. Fron;er, Eur. J. Org. Chem. 2013, 3621– 3633
• 3. W. He, X. Sun, A. J. Fron;er, J. Am. Chem. Soc. 2003, 125, 14278–14279
• 4. T. N. Grant, C. J. Rieder, F. G. West, Chem. Commun. 2009, 5676–5688 • 5. T. Jin, Y. Yamamoto, Org. Le>. 2008, 10, 3137–3139 • 6. G. Y. Lin, C. Y. Yang, R. S. Liu, J. Org. Chem. 2007, 72, 6753–6757. • 7. M. A. Tius, Acc. Chem. Res. 2003, 36, 284–290.
14
Questions?
15