Catalytic Enantioselective Aldol Reactions of Unprotected Carboxylic Acids under Phosphine Oxide Catalysis

Abstract

The first catalytic enantioselective aldol reaction of various unprotected carboxylic acids is described. In the presence of ac hiral bis(phosphine oxide) as aL ewis base catalyst, carboxylic acids were activated with silicon tetrachloride to form the corresponding bis(trichlorosilyl)enediolates in situ, which subsequently underwent an aldol reaction with an aldehyde or aketone to produce b-hydroxycarboxylic acids in high enantioselectivities of up to 92 %ee. Scheme 1. Enantioselective aldol reactions of carboxylic acids.[*] Dr.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Boron‐Catalyzed α‐Functionalizations of Carboxylic Acids

“…Later, Ramachandran showcased that the combination of R 2 BX and NEt 3 is also effective [16,17] . While these precedents showed the utility of boron compounds for carboxylic acid‐aldol reaction, the catalytic asymmetric aldol reaction of carboxylic acids remained unprecedented [18] …”

Siloxy Esters as Traceless Activators of Carboxylic Acids: Boron‐Catalyzed Chemoselective Asymmetric Aldol Reaction**

“…[13] Kotani and Nakajima recently reported the first catalytic asymmetric aldol reaction of carboxylic acids (Scheme 1d). [14] Their method employed chiral Lewis base activation of bis(trichlorosilyl)enediolates,p repared from carboxylic acids through treatment with tetrachlorosilane and as terically hindered amine base.H owever,h igh Lewis acidities of tetrachlorosilane and trichlorosilyl group raise potential challenges in practical applicability to complex substrates bearing multiple sensitive functional groups. [15] Indeed, despite the high utility,c atalytic asymmetric aldol reactions applicable to multifunctional substrates at late stages are still underdeveloped.…”