Enantioselective Desymmetrization of Diesters

Abstract

The desymmetrization of prochiral diesters with a chiral phosphoric acid catalyst to produce highly enantioenriched lactones in excellent yield is reported. The process is easily scaled and accommodates a variety of substitution patterns, many of which result in the generation of an enantioenriched all-carbon quaternary center. Manipulation of lactone product to useful small building blocks is also described.

Enantioselective Synthesis of α,α-Disubstituted Lactones via a Chiral Brønsted Acid Catalyzed Intramolecular Cyclization

“…5 Disubstituted hydroxy tert -butyl malonates 3a–3g were readily prepared in 3 steps and in the presence of Binol based chiral Brønsted acid, ( R )- or ( S ) - TRIP ( 4 ), enantioenriched lactones 5a–5g were formed (Table 1). Coordination of the chiral phosphoric acid through one or more hydrogen bonds to the substrate likely leads to a rigid transition state which allows for discrimination of the enantiotopic ester groups.…”

Visible Light and Molecular Iodine‐Mediated Diastereoselective Intermolecular Lactonization of Styrenes with Carbonyls

“…The first method is performed by the intramolecular cyclization reaction of linear starting materials (Scheme a); the methodology is generally used as a first choice for the synthesis of lactones because the methods are generally reliable and robust . The diastereoselective and enantioselective synthesis of lactones was achieved using the abovementioned approach . Although considerable progress has been made in the synthesis of lactones via the cyclization reaction, a multi‐step synthesis to obtain linear starting materials is frequently required.…”

Organocatalytic enantioselective desymmetrisation

“…241 This approach is an alternative to halolactonisations and protolactonisations of alkenoic acids, also used as desymmetrising strategies. 241 This approach is an alternative to halolactonisations and protolactonisations of alkenoic acids, also used as desymmetrising strategies.…”