Stereoselective Synthesis ofanti-α-(Difluoromethyl)-β-amino Alcohols by Boronic Acid Based Three-Component Condensation. Stereoselective Preparation of (2S,3R)-Difluorothreonine

Abstract

Starting from optically active 3,3-difluorolactaldehyde, an alkenyl or aryl boronic acid, and an amine, a one-step three-component methodology was developed for the stereoselective preparation of anti-alpha-(difluoromethyl)-beta-amino alcohols. beta-Furyl-substituted anti-alpha-(difluoromethyl)-beta-amino alcohol was further elaborated to form (2S,3R)-difluorothreonine in high yield and ee.

S‐((Phenylsulfonyl)difluoromethyl)thiophenium Salts: Carbon‐Selective Electrophilic Difluoromethylation of β‐Ketoesters, β‐Diketones, and Dicyanoalkylidenes

“…Thus, the functionalization of organic molecules with fluorinated moieties has been a key strategy in drug development. Among fluorinated functional groups, the difluoromethyl (CF 2 H) group has clear advantages: it is isosteric and isopolar to a hydroxy (OH)2 and thiol (SH)3 unit. The CF 2 H group can also act as a more lipophilic hydrogen donor than OH and NH groups through hydrogen bonding,1n, 4–6 thus making it an interesting moiety with respect to the design of bioactive molecules.…”

Furan Oxidations in Organic Synthesis: Recent Advances and Applications

“…Thus, the procedure is quite adequate for highly water soluble compounds like 3 which can be isolated and further hydrolyzed to furnish carboxylic acid 4 (Scheme 6) [32]. Thus, the procedure is quite adequate for highly water soluble compounds like 3 which can be isolated and further hydrolyzed to furnish carboxylic acid 4 (Scheme 6) [32].…”

A General and Selective Rhodium‐Catalyzed Reduction of Amides, N‐Acyl Amino Esters, and Dipeptides Using Phenylsilane

“…Additionally,t he Petasis three-component reactions applying boronic acids, amines,a nd glyoxylic acid are employed fort he diastereoselectives ynthesis of a-amino acid ester derivatives. [7] Other versatile approaches consist of the addition of electrophiles to glycine enolate derivatives, and conversely,o ft he addition of nucleophiles to electrophilicg lycine templates, both of which have been used successfully as methodologies to access unnaturala mino acid derivatives. [8] Moreover,c atalytic Mannichr eactions offer elegant access for the synthesis of baminoesters.…”