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. 2013 Feb 1;15(3):444-7.
doi: 10.1021/ol303040r. Epub 2013 Jan 15.

Synthesis of isoquinuclidines from highly substituted dihydropyridines via the Diels-Alder reaction

Rhia M Martin  1 , Robert G Bergman, Jonathan A Ellman
Affiliations

Synthesis of isoquinuclidines from highly substituted dihydropyridines via the Diels-Alder reaction

Rhia M Martin et al. Org Lett. .

Abstract

A stereo- and regioselective Diels-Alder reaction for the synthesis of highly substituted isoquinuclidines from dihydropyridines and electron-deficient alkenes has been developed. While reactions with activated dienophiles proceed readily under thermal conditions, the use of Lewis acid additives is necessary to facilitate cycloadditions for less reactive alkenes. This procedure affords the target compounds in high yields and diastereoselectivities.

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Figures

Figure 1
Figure 1
Relative Configuration and Ball-and-Stick Representation of 3g.
Scheme 1
Scheme 1
Rh-Catalyzed C–H Functionalization Provides Versatile 1,2-Dihydropyridine Intermediates
Scheme 2
Scheme 2. Substrate Scope of Diels-Alder Reactionsa
a Yields correspond to the yields of isolated products. The diastereoselectivities were determined by 1H NMR analysis of unpurified material. b ZnCl2 (1.1 equiv), 0.5 M CH2Cl2, 0 °C, 6 h. c N-phenyl maleimide (1.05 equiv), 0.1 M CH2Cl2, rt. d Neat, 105 °C. e 24 h. f 72 h. g N-phenyl maleimide (1.05 equiv), 0.5 M CH2Cl2, 50 °C. h 48 h.
See this image and copyright information in PMC

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