Diastereodivergent organocatalytic asymmetric vinylogous Michael reactions

Abstract

One of the major challenges of modern asymmetric catalysis is the ability to selectively control the formation of all diastereoisomers of reaction products possessing multiple stereocenters. Pioneers of such diastereodivergent catalytic asymmetric processes have focused on reactions where the newly formed stereogenic centres are proximal to the active carbonyl group. To date, however, diastereodivergent reactions at remote positions remain an unmet challenge. Herein, we describe a catalyst-controlled diastereodivergence in the formation of remote stereocenters in the direct vinylogous Michael reactions of b, g-unsaturated butenolides to a, b-unsaturated ketones. The reactions are enabled by two complementary, non-enantiomeric multifunctional catalysts, which mutually activate and organise both reactants, affording either the syn-or anti-adduct with high diastereo-and enantioselectivity. These two catalytic systems are also applicable in the Mukaiyama-Michael reactions and tandem Michael-Michael reactions.

Catalytic Strategies for Diastereodivergent Synthesis

“…Besides, similar diastereodivergent catalytic systems were suitable when the nucleophiles were γ‐substituted‐ N ‐Boc‐2‐( tert ‐butyldimethylsilyl) oxy‐pyrroles, γ‐substituted butenolides or oxindoles . What's more, Ye also found chiral diamine catalysts could realize the diastereodivergent asymmetric Michael addition of 2‐oxindoles to α,β‐unsaturated ketones …”

“…Ye developed a diastereodivergent direct vinylogous Michael reactions of β,γ‐unsaturated butenolides to α,β‐unsaturated ketones, forming remote vicinal quaternary and tertiary stereogenic centres, by applying different multi‐amine catalysts 31 and 32 (Scheme ) . The primary amine group of catalyst activates the enone through generation of an iminium intermediate, and the other amines control the direction of the nucleophile's attack by hydrogen‐bonding interactions.…”

Angelica Lactones: From Biomass‐Derived Platform Chemicals to Value‐Added Products

“…Besides conjugated aldehydes, α,β‐unsaturated ketones have also been used as Michael acceptors in the presence of angelica lactones. Seminal work in this subject was reported by Dixon's group, who disclose the generation of anti and syn adducts from catalyst‐controlled diastereodivergence in the direct Michael addition of β,γ‐unsaturated butenolides to α,β‐unsaturated ketones 33 (Scheme ) . To obtain high enantioselectivity of one diastereoisomer, the authors develop two multifunctional primary amine catalysts.…”

A Scaffold‐Diversity Synthesis of Biologically Intriguing Cyclic Sulfonamides

“…In the last reaction of the branching pathway, a Mannich‐type addition of α‐angelica lactone as nucleophile to ketimine moiety in 1 was explored . In this way, we targeted molecular complexity both in terms of consecutive quaternary stereocenters in the product, as well as having a natural product fragment—the lactone ring—with a free rotation around the newly constructed bond.…”