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. 2018 Feb 16;20(4):1146-1149.
doi: 10.1021/acs.orglett.8b00076. Epub 2018 Feb 8.

Asymmetric and Site-Selective [3 + 2]-Annulations for the Synthesis of High-Value Bicyclic Lactams

Dimitris Kalaitzakis  1 , Manolis Sofiadis  1 , Myron Triantafyllakis  1 , Konstantinos Daskalakis  1 , Georgios Vassilikogiannakis  1
Affiliations

Asymmetric and Site-Selective [3 + 2]-Annulations for the Synthesis of High-Value Bicyclic Lactams

Dimitris Kalaitzakis et al. Org Lett. .

Abstract

Asymmetric and site-selective formal [3 + 2]-annulations of γ-alkyl-β,γ-unsaturated γ-lactams with α,β-unsaturated aldehydes have been developed. These organocatalysed transformations yield high value enantioenriched bicyclic γ-lactams with up to four new stereocenters (sometimes including a quarternary carbon). The overall transformation starts from simple and readily accessible furans and oversees a rapid, controlled, and dramatic enhancement in 3D complexity.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Selective Formal [3 + 2]-Annulations of β,γ-Unsaturated γ-Lactams
Scheme 2
Scheme 2. Asymmetric [3 + 2]-Annulations of β,γ-Unsaturated γ-Lactams 2 with α,β-Unsaturated Aldehydes 4
All the reactions were performed using 0.2 mmol of 2. Determined by crude 1H NMR spectrum. Determined by chiral HPLC analysis of the major diastereoisomer. Isolated yield for major diastereoisomer.
Scheme 3
Scheme 3. Asymmetric [3 + 2]-Annulations of β,γ-Unsuturated γ-Lactams 3 with α,β-Unsaturated Aldehydes 4
All of the reactions were performed using 0.2 mmol of 3 or 1 (in case of cond Q). Determined by the crude 1H NMR spectrum. Determined by chiral HPLC analysis of the major diastereoisomer. Isolated yield for the major diastereoisomer.
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