Primary trifluoroborate-iminiums enable facile access to chiral α-aminoboronic acids via Ru-catalyzed asymmetric hydrogenation and simple hydrolysis of the trifluoroborate moiety

Abstract

This work describes the first preparation and application of primary trifluoroborate‐iminiums (pTIMs) as new, easily accessible and valuable class of organoboron derivatives. An array of structurally diverse pTIMs was prepared...

Enantioselective Synthesis of α-Aminoboronic Acid Derivatives via Copper-Catalyzed N-Alkylation

“…The enantioselective synthesis of chiral α-aminoboronic acids and their derivatives is an important goal in organic chemistry, since they are subunits in an array of bioactive compounds (antibacterial, anticancer, antiviral, etc., including Velcade; Figure A − ) − and serve as versatile intermediates in synthesis. − Whereas early approaches to controlling the α stereocenter relied on diastereoselective processes via, for example, chiral auxiliaries, − methods wherein a chiral catalyst controls that stereocenter have begun to emerge, including the hydroamination of alkenylboronates, , borylation of aldimines , and ketimines, hydroboration of enamides, tandem hydroboration–hydroamination of terminal alkynes, and hydrogenation of boryl-substituted iminiums …”

“…8−10 Whereas early approaches to controlling the α stereocenter relied on diastereoselective processes via, for example, chiral auxiliaries, 11−15 methods wherein a chiral catalyst controls that stereocenter have begun to emerge, including the hydroamination of alkenylboronates, 16,17 bor-ylation of aldimines 18,19 and ketimines, 20 hydroboration of enamides, 21 tandem hydroboration−hydroamination of terminal alkynes, 22 and hydrogenation of boryl-substituted iminiums. 23 Figure 1B outlines a complementary approach to the catalytic asymmetric synthesis of α-aminoboronic acid derivatives, starting with commercially available linchpin A. First, substitution by a carbon nucleophile generates racemic B, 24 and then asymmetric substitution by a nitrogen nucleophile provides enantioenriched target C (challenges: control of stereochemistry, elimination of HCl, overalkylation of NH 2 R, etc.).…”

Nickel-Catalyzed 1,1-Aminoborylation of Unactivated Terminal Alkenes

“…Encouraged by the results compiled in Scheme , we focused our attention on exploring the synthetic applicability of our Ni-catalyzed 1,1-aminoborylation of unactivated olefins. As shown in Scheme , simple exposure of 4a to hexamethyldisiloxane (HMDSO) gave access to 5a in quantitative yield . Subsequently, we turned our attention to the venerable Matteson homologation as a vehicle to generate β-aminoboronic esters from the corresponding α-substituted congeners.…”

Hydrogen-Bonding Ability of Noyori–Ikariya Catalysts Enables Stereoselective Access to CF3-Substituted syn-1,2-Diols via Dynamic Kinetic Resolution

“…Remarkably, the dialkylketones 2o – 2q were reduced to the corresponding syn -diols with >95% ee using C4 or C5 ; the first one was more diastereoselective for the synthesis of the benzyl substituted 3o , and C5 was optimal for the synthesis of 3p and 3q . In the case of dialkylketone reduction, the stereoselectivity could (in the absence of appropriately positioned aromatic ring on the substrate) rely either on hydrogen bonding of CF 3 CH­(OH) moiety to SO 2 of the catalyst or on CF 3 –η 6 -arene attractive interaction. , The two hydrogenation modes would deliver the opposite enantioselectivity, which is often the case for the Noyori–Ikariya reduction of dialkyl vs alkyl aryl ketones. − Based on the SCXRD analysis of 3o , the order of elution in chiral chromatographic analysis, and computational analysis of the transition states during the reduction of the model substrate, where no CF 3 –η 6 -arene attractive interaction has been identified during Re -face attack (Figure c and d), we assigned to the alkyl-substituted diols 3o , 3p , and 3q the same absolute configuration as to the (het)­aryl-substituted 3a – 3n .…”

“… 13 , 48 The two hydrogenation modes would deliver the opposite enantioselectivity, which is often the case for the Noyori–Ikariya reduction of dialkyl vs alkyl aryl ketones. 49 − 51 Based on the SCXRD analysis of 3o , the order of elution in chiral chromatographic analysis, and computational analysis of the transition states during the reduction of the model substrate, where no CF 3 –η 6 -arene attractive interaction has been identified during Re -face attack ( Figure 3 c and 3 d), we assigned to the alkyl-substituted diols 3o , 3p , and 3q the same absolute configuration as to the (het)aryl-substituted 3a – 3n .…”