Regio- and diastereoselective Reformatsky reaction of chiral fluoroalkyl α,β-unsaturated N - tert -butanesulfinyl ketimines: Efficient asymmetric synthesis of β-fluoroalkyl β-vinyl β-amino esters

Regio‐ and Diastereoselective Conjugate Addition of Grignard Reagents to Chiral Fluoroalkyl α,β‐Unsaturated N‐tert‐Butanesulfinyl Ketimines: Synthesis of Optically Active Fluorinated Enamines and Derivatives

“…Our group has had a longstanding interest in the selective conversions of α,β‐unsaturated N ‐ tert ‐butanesulfinyl ketimines. We have developed regioselective asymmetric reduction, [14] aza‐Henry reaction, [15] Strecker reaction, [16] and Reformatsky reaction [5b] of chiral fluoroalkyl α,β‐unsaturated N ‐ tert ‐butanesulfinyl ketimines. In addition, we have disclosed regio‐ and diastereoselective 1,2‐addition of organolithium reagents to chiral fluoroalkyl α,β‐unsaturated N ‐ tert ‐butanesulfinyl ketimines (Scheme 1b) [17] and trifluoromethylation [18] of α,β‐unsaturated N ‐ tert ‐butanesulfinyl ketimines to achieve asymmetric synthesis of α‐tertiary fluoroalkyl allylic amines.…”

Chiral N‐tert‐Butylsulfinyl Imines: New Discoveries

“…The same reaction applied to imines 9 led to the formation of amines 166 with high diastereoselectivity (Scheme 71). [92] Transition state TS was proposed to explain the stereochemical outcome of the process.…”

Synthesis of Chiral β-Fluoroalkyl β-Amino Acid Derivatives via Palladium-Catalyzed Hydrogenation

“…For example, CF 3 -Ac docetaxel is used against human cancer cell lines (Figure , I ), − and ψ [CH­(CF 3 )­NH]-retro-thionphane is used as a neutral endopeptidase inhibitor (Figure , II ) . Thus, the enantioselective syntheses of β-fluoroalkyl β-amino acid derivatives have attracted a great deal of interest, and many efficient methods have been developed including chiral auxiliary strategies and catalytic methods, − such as isomerization of fluorinated imines, the catalytic asymmetric Mannich reaction of fluorinated imines, and aza-Michael addition of fluorinated imines . Although some progress has been made in the synthesis of β-fluoroalkyl β-amino acid derivatives, these existing routes have several drawbacks involving poor enantioselectivities, the stoichiometric amounts of chiral auxiliaries needed, and so on, thus prohibiting their further application.…”