α,α‐Difluoro‐α‐(trimethylsilyl)acetamides as Versatile Reagents for the Preparation of Difluorinated Aldol and Mannich Adducts

Abstract

Thev ery efficient addition of a,a-difluoroa-(trimethylsilyl)acetamides to aldehydes,k etones and N-(tert-butanesulfinyl)imines is described. The reactioni sp romoted by ac atalytic amount of tetran-butylammonium diphenyltrifluorosilicate (TBAT) and high yields,a sw ell as very high stereoselectivities in the case of N-(tert-butanesulfinyl)imines,a re achieved. Thes ynthetic potentialo ft his method is il-lustrated by the conversion of the resulting products to b-hydroxy ketones,d iols and b-amino alcohols by addition of various Grignard reagents or reduction of the amide moiety.

Methods for the Synthesis of α,α‐Difluoroketones

“…[42] The alkylation of simple difluorinated morpholino amides, even those bearing an unprotected hydroxyl group proceeds well, although 4 equivalents of Grignard reagent were used to form ketone 40 (Scheme 15). [43] Much more common has been the alkylation of difluorinated Weinreb amides, which proceed with excellent control in preventing any over-alkylation (Scheme 15). [44] These can be formed either by action of N,Odimethylhydroxylamine on a difluorinated ester in the presence of AlCl 3 , or from the acid chloride.…”

Enantioselective Aldol Reaction with Difluoroenoxysilanes Catalyzed by Cationic Palladium Aqua Complexes

“…[11,12] Our own contribution to these "nondifluoroenoxysilane" approaches relied on one-pot strategies from CF 3 TMS and acylsilanes or on the use of α,α-difluoro-αtrimethylsilylacetamides. [13] Some catalytic enantioselective additions of difluoroenolate precursors to various carbonyl-type electrophiles have been reported, [10a,d-e,h,11b,12a] but examples of classical aldol reaction on standard aldehydes remain scarce (scheme 1). [11e,14] We wish to report herein a novel catalytic enantioselective addition of difluoroenoxysilanes onto aromatic aldehydes, using cationic palladium aqua complexes.…”

Biomimetic enantioselective synthesis of β,β-difluoro-α-amino acid derivatives

“…The group of Ayi reported the enzymatic hydrolysis of β,β -difluoro- α -amino esters via kinetic resolution 35 . Liu and his colleagues disclosed an effective method for controlling enantioselectivity by introducing chiral auxiliaries 36 – 40 . Uneyama uncovered an amazing asymmetric hydrogenation of α-fluoroiminoesters via catalytic amount of chiral BINAP ligand and palladium 41 – 43 .…”