Direct Catalytic Asymmetric Doubly Vinylogous Michael Addition of α,β-Unsaturated γ-Butyrolactams to Dienones

Xiaodong Gu; Tingting Guo; Yuanyuan Dai; Allegra Franchino; Jie Fei; Chuncheng Zou; Darren J Dixon; Jinxing Ye

doi:10.1002/anie.201504276

Direct Catalytic Asymmetric Doubly Vinylogous Michael Addition of α,β-Unsaturated γ-Butyrolactams to Dienones

Angew Chem Int Ed Engl. 2015 Aug 24;54(35):10249-53. doi: 10.1002/anie.201504276. Epub 2015 Jul 15.

Authors

Xiaodong Gu¹, Tingting Guo¹, Yuanyuan Dai¹, Allegra Franchino², Jie Fei¹, Chuncheng Zou¹, Darren J Dixon³, Jinxing Ye⁴

Affiliations

¹ Engineering Research Centre of Pharmaceutical Process Chemistry, Ministry of Education, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237 (China).
² Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA (UK).
³ Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA (UK). [email protected].
⁴ Engineering Research Centre of Pharmaceutical Process Chemistry, Ministry of Education, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237 (China). [email protected].

Abstract

An asymmetric doubly vinylogous Michael addition (DVMA) of α,β-unsaturated γ-butyrolactams to sterically congested β-substituted cyclic dienones with high site-, diastereo-, and enantioselectivity has been achieved. An unprecedented DVMA/vinylogous Michael addition/isomerization cascade reaction affords chiral fused tricyclic γ-lactams with four newly formed stereocenters.

Keywords: asymmetric catalysis; conjugation; cyclizations; nucleophilic addition; organocatalysis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkenes / chemistry*
Catalysis
Crystallography, X-Ray
Ketones / chemistry*
Lactams / chemistry*
Models, Molecular
Molecular Structure
Stereoisomerism

Substances

Alkenes
Ketones
Lactams