Synthesis of enantioenriched α-heteroatom functionalised aldehydes by chiral organocatalysis and their synthetic applications

Abstract

Asymmetric organocatalysis has proven to be one of the most versatile methods for the enantioselective α-functionalisation of aldehydes. Initially pioneered by the report of an L-proline catalysed intermolecular aldol reaction,...

Diastereoselective Petasis‐Borono‐Mannich Crotylation Reactions of Chiral α‐Heteroatom (F, OBz, OH) Aldehydes: Rapid Access to Valuable Mono and Bicyclic Heterocyclic Scaffolds

“…[15] The use of the PBM reaction in crotylation reactions has been limited to achiral aldehydes (Scheme 2a). [11,16] The development of such reactions to include chiral α-heteroatom [17] (X=F, OBz or OH) aldehydes would expand the scope of the PBM reaction providing products having three contiguous stereogenic centres. Herein we report the results of our study of the crotylation reactions of chiral α-heteroatom aldehydes with the focus on the crotylation reactions of chiral αfluoroaldehydes [18] due to the importance of fluorine as a substituent in drug, [19] chiral ligand and organocatalyst development.…”

Stereoselective Electrophilic Chlorination of β,β-Disubstituted Enesulfinamides with Chloramine-T: Asymmetric Synthesis of Acyclic α,α-Disubstituted α-Chlorinated Carbonyl Surrogates

“…Enantioenriched α-chloro-substituted carbonyls and their aza-analogs are useful synthetic precursors capable of undergoing diverse chemical transformations. One such transformation is the stereoselective S N 2 displacement at a chlorine-containing stereocenter using carbon- or heteroatom-based nucleophiles, which facilitates the generation of a wide range of functionalized stereocenters . The direct introduction of a chlorine atom into the α-position of the carbonyl group in a stereoselective manner is an effective approach to accessing these chloro compounds.…”

High atomic utilization conversion of ethers into furancarbaldehydes via an ether oxidation iminium-ion activation cascade strategy

“…Notably, in our previous work, the alkyl component released by oxidation of cinnamyl alkyl ether did not participate in the subsequent reaction, resulting in low atomic utilization. 1–25 However, we recently envisaged designing a novel ether oxidation cascade with high atomic utilization: the enol fragment released by ether oxidation continues to participate in the subsequent cascade as a reactant, instead of leaving like a protective group.…”

“…9 Organocatalytic enal-derived iminium-enamine activated asymmetric transformations have been demonstrated as powerful approaches for constructing enantiomerically enriched and functionalized aldehydes. [10][11][12][13][14][15][16][17][18][19][20][21] To our knowledge, the oxidative cleavage of cinnamyl alkyl ethers to access enal-derived iminium ions should be an attractive synthetic strategy in which ethers can be used as "masked" aldehydes for further iminium catalysis. Therefore, we previously reported an oxidative iminium-ion activation strategy using cinnamyl alkyl ethers as substrates to synthesis α-spirocyclopropane derivatives 22 (Scheme 1a).…”