Regio‐ and Enantioselective Synthesis of Trifluoromethyl‐Substituted Homoallylic α‐Tertiary NH₂‐Amines by Reactions Facilitated by a Threonine‐Based Boron‐Containing Catalyst

Abstract

A method for catalytic regio‐ and enantioselective synthesis of trifluoromethyl‐substituted and aryl‐, heteroaryl‐, alkenyl‐, and alkynyl‐substituted homoallylic α‐tertiary NH2‐amines is introduced. Easy‐to‐synthesize and robust N‐silyl ketimines are converted to NH‐ketimines in situ, which then react with a Z‐allyl boronate. Transformations are promoted by a readily accessible l‐threonine‐derived aminophenol‐based boryl catalyst, affording the desired products in up to 91 % yield, >98:2 α:γ selectivity, >98:2 Z:E selectivity, and >99:1 enantiomeric ratio. A commercially available aminophenol may be used, and allyl boronates, which may contain an alkyl‐, a chloro‐, or a bromo‐substituted Z‐alkene, can either be purchased or prepared by catalytic stereoretentive cross‐metathesis. What is more, Z‐trisubstituted allyl boronates may be used. Various chemo‐, regio‐, and diastereoselective transformations of the α‐tertiary homoallylic NH2‐amine products highlight the utility of the approach; this includes diastereo‐ and regioselective epoxide formation/trichloroacetic acid cleavage to generate differentiated diol derivatives.

Enantioselective Catalyzed Synthesis of Amino Derivatives Using Electrophilic Open‐Chain N‐Activated Ketimines

“…Recently, N‐ trimethylsilyl ketimines 4 have been directly employed in the enantioselective catalyzed reaction with allylboron reagents but their use still remains rather underdeveloped [11] . A recently devised procedure exploits a palladium‐catalyzed carbonylation of N ‐unsubstituted diarylketimines 6 using aryl bromides in the presence of phosphinite ligand 7 (Scheme 2).…”

Sulfonate N‐Heterocyclic Carbene–Copper Complexes: Uniquely Effective Catalysts for Enantioselective Synthesis of C−C, C−B, C−H, and C−Si Bonds

“…[180] Most recently,w ed emonstrated that reactions of trifluoromethyl-substituted silyl ketimines with Z-allyl boronate compounds may be promoted by an aminophenol-boryl catalyst, directly affording unprotected a-tertiary amine in high enantiomeric purity. [181] It should be noted that trifluoromethyl-substituted NH-ketimines are unstable and therefore not suitable for sulfonate NHC-Cucatalyzed processes (see Scheme 81;s ee also Zhang, Scheme 80). Scheme 78.…”

Sulfonate N‐Heterocyclic Carbene–Copper Complexes: Uniquely Effective Catalysts for Enantioselective Synthesis of C−C, C−B, C−H, and C−Si Bonds

“…[180] Most recently,w ed emonstrated that reactions of trifluoromethyl-substituted silyl ketimines with Z-allyl boronate compounds may be promoted by an aminophenol-boryl catalyst, directly affording unprotected a-tertiary amine in high enantiomeric purity. [181] It should be noted that trifluoromethyl-substituted NH-ketimines are unstable and therefore not suitable for sulfonate NHC-Cucatalyzed processes (see Scheme 81;s ee also Zhang, Scheme 80).…”