A Regulation of Regiodivergent Routes for Enantioselective Aldol Addition of 2-Alkyl Allenoates with Aldehydes: α-Addition versus γ-Addition

Abstract

A method for the regioselective asymmetric aldol addition of 2-alkyl allenoates with aldehydes to provide an α- or γ-adduct depending on the aldehyde pair is reported. In most cases, except enals, a mixture of a chiral bromoborane with 2-alkyl allenoates in the presence of iPrNEt can react with aldehydes to provide efficient γ-addition products as single isomers containing axial and central chirality. On the other hand, observations indicate that enals undergo α-addition to yield highly functionalized adducts, including an α-carbon quaternary center in high levels of diastereo- and enantioselectivity.

Kinetic Resolution of Racemic Aldehydes through Asymmetric Allenoate γ-Addition: Synthesis of (+)-Xylogiblactone A

“…In the course of our research program aimed at finding new synthetic methods, we disclosed our investigations on the unprecedented γ-addition of 2-alkylallenoates to normal aldehydes to construct a unique structure with axial and central chirality . The reaction usually produced a γ-adduct as a single isomer in regio- and stereochemically pure form .…”

“… On the basis of the reasonable speculation that the stereochemical model for this regio- and stereochemically specific transformation of the allenoate γ-addition is highly organized, the investigation of such an organization like a kinetic-resolution process assumes another importance. On a positive note, we envisaged that an anti -Felkin–Anh adduct could be a major product after the extensive analysis of cyclic stereochemical models to regulate stereoselectivity based on our previous observation …”

“…In light of the above results for the kinetic resolution of 2-silyloxyaldehydes (±)- 6 via the allenoate γ-addition, we next turned our attention to the application of this approach for the synthesis of naturally occurring (+)-xylogiblactone A ( 1a ). Structurally unique xylogiblactone A along with B and C was isolated from the ethyl acetate extracts of the fermented broth of Xylotumulus gibbisporus YMJ863, which exhibits antifungal activities . Structurally related butenolide (+)-hypoxylactone was isolated from a different source, the fermentation broth of the facultative marine Hypoxylon croceum together with a new sordarin derivative …”

Deciphering the Chameleonic Chemistry of Allenols: Breaking the Taboo of a Onetime Esoteric Functionality

“…The methodology was also applied for the kinetic resolution of racemic aldehydes, and further generation of the butenolide core of the natural product (+)-xilogiblactone A. 110 − 113 …”

Gold-Catalyzed Reactions of Specially Activated Alkynes, Allenes, and Alkenes

“…This transformation involves the formation of key intermediate 1077, which evolves into 1076 by a sequence of fragmentation of the tert-butyl group and protodeauration. This reaction has been employed by Yu, Kim and coworkers as a means to substantiate a new access to allenes 441 and was also exploited in the total synthesis of (+)-Xylogiblactone A (Scheme 251, part B). 442 The group of Hammond has studied this transformation in greater detail with respect to its mechanism and the reactivity of its intermediates.…”