Enantioselective Total Synthesis of (‐)‐Finerenone using Asymmetric Transfer Hydrogenation

(−)‐Finerenone is a nonsteroidal mineralocorticoid receptor antagonist currently in phase III clinical trials for the treatment of chronic kidney disease in type 2 diabetes. It contains an unusual dihydronaphthyridine core. We report a 6‐step synthesis of (−)‐finerenone, which features an enantioselective partial transfer hydrogenation of a naphthyridine using a chiral phosphoric acid catalyst with a Hantzsch ester. The process is complicated by the fact that the naphthyridine exists as a mixture of two atropisomers that react at different rates and with different selectivities. The intrinsic kinetic resolution was converted into a kinetic dynamic resolution at elevated temperature, which enabled us to obtain (−)‐finerenone in both high yield and high enantioselectivity. DFT calculations have revealed the origin of selectivity.<br/

Borane-Catalyzed Ring-Opening and Ring-Closing Cascades of Furans Leading to Silicon-Functionalized Synthetic Intermediates

The conversion of renewable biomass resources to synthetically valuable chemicals is highly desirable, but remains a formidable challenge in regards to the substrate scope and reaction conditions. Here we present the development of tris(pentafluorophenyl)borane–catalysed conversion of furans via ring-opening and closing cascade processes to afford siliconfunctionalized synthetic chemicals under transition metal-free conditions. The furan ring-opening with hydrosilanes is highly efficient (TON up to 2,000) and atom-economical without forming any byproduct to give rise to a-silyloxy-(Z)-alkenyl silanes. Additional equivalents of silane smoothly induce a subsequent B(C6F5)3-catalysed cyclization of initially formed olefinic silane compounds to produce anti-(2-alkyl)cyclopropyl silanes, another versatile synthon being potentially applicable in the synthesis of natural products and pharmacophores. (c) The Author(s) 201611sciescopu

Selective Silylative Reduction of Pyridines Leading to Structurally Diverse Azacyclic Compounds with the Formation of sp3 C-Si Bonds

Tris(pentafluorophenyl)borane-catalyzed silylative reduction of pyridines has been developed giving rise to the formation of sp3 C-Si bonds selectively beta to the nitrogen atom of azacyclic products. Depending on the position and nature of pyridine substituents, structurally diverse azacycles are obtained with high selectivity under the borane catalysis. Mechanistic studies elucidated the sequence of hydrosilylation in this multiple reduction cascade: 1,2- or 1,4-hydrosilylation as an initial step depending on the substituent position, followed by selective hydrosilylation of enamine double bonds eventually affording β-silylated azacyclic compounds. © 2015 American Chemical Society133321sciescopu

Boron-Catalyzed Hydrogenative Reduction of Substituted Quinolines to Tetrahydroquinolines with Hydrosilanes

A metal-free procedure for the hydrogenative reduction of substituted N-heteroaromatics has been developed by using hydrosilanes as reducing agents. The optimized conditions were successfully applied to the reactions of quinolines, quinoxalines, and quinoline N -oxides. They were also effective for the reduction of quinolines bearing amino or hydroxy groups, where H 2 was evolved through dehydrogenative silylation of the amine or hydroxy moieties. Preliminary mechanistic studies revealed that the initial step in the catalytic cycle involves 1,4-addition of the hydrosilane to the quinoline to give a 1,4-dihydroquinoline; this is followed by (transfer) hydrogenation to deliver the tetrahydroquinoline as the final product. © Georg Thieme Verlag Stuttgart.New York1331sciescopu

Selective Silylative Reduction of Pyridines Leading to Structurally Diverse Azacyclic Compounds with the Formation of sp³ C–Si Bonds

Tris­(pentafluorophenyl)­borane-catalyzed silylative reduction of pyridines has been developed giving rise to the formation of sp³ C–Si bonds selectively beta to the nitrogen atom of azacyclic products. Depending on the position and nature of pyridine substituents, structurally diverse azacycles are obtained with high selectivity under the borane catalysis. Mechanistic studies elucidated the sequence of hydrosilylation in this multiple reduction cascade: 1,2- or 1,4-hydrosilylation as an initial step depending on the substituent position, followed by selective hydrosilylation of enamine double bonds eventually affording β-silylated azacyclic compounds

Borane catalysed ring opening and closing cascades of furans leading to silicon functionalized synthetic intermediates

The conversion of renewable biomass resources to synthetically valuable chemicals is highly desirable, but remains a formidable challenge in regards to the substrate scope and reaction conditions. Here we present the development of tris(pentafluorophenyl)borane-catalysed conversion of furans via ring-opening and closing cascade processes to afford silicon-functionalized synthetic chemicals under transition metal-free conditions. The furan ring-opening with hydrosilanes is highly efficient (TON up to 2,000) and atom-economical without forming any byproduct to give rise to α-silyloxy-(Z)-alkenyl silanes. Additional equivalents of silane smoothly induce a subsequent B(C6 F5)3 -catalysed cyclization of initially formed olefinic silane compounds to produce anti-(2-alkyl)cyclopropyl silanes, another versatile synthon being potentially applicable in the synthesis of natural products and pharmacophores. © The Author(s) 2016113121sciescopu

Boron-Catalyzed Silylative Reduction of Nitriles in Accessing Primary Amines and Imines

Silylative reduction of nitriles was studied under transition metal-free conditions by using B(C6F5)3 as a catalyst with hydrosilanes as a reductant. Alkyl and (hetero)aryl nitriles were efficiently converted to primary amines or imines under mild conditions. The choice of silanes was found to determine the selectivity: while a full reduction of nitriles was highly facile, the use of sterically bulky silanes allowed for the partial reduction leading to Nsilylimines. © 2015 American Chemical Society126241sciescopu

Chemoselective silylative reduction of conjugated nitriles under metal-free catalytic conditions: β-silyl amines and enamines

Abstract The B(C6F5)3-catalyzed silylative reduction of conjugated nitriles has been developed to afford synthetically valuable β-silyl amines. The reaction is chemoselective and proceeds under mild conditions. Mechanistic elucidation indicates that it proceeds by rapid double hydrosilylation of the conjugated nitrile to an enamine intermediate which is subsequently reduced to the β-silyl amine, thus forming a new C(sp3)-Si bond. Based on this mechanistic understanding, a preparative route to enamines was also established using bulky silanes. Triple whammy: The B(C6F5)3-catalyzed silylative reduction of conjugated nitriles has been developed to afford synthetically valuable β-silyl amines. Based on the mechanistic understanding, a preparative route to enamines was also established using bulky silanes. The reaction is chemoselective, has a broad scope, and proceeds under mild reaction conditions. The mechanism of the triple hydrosilylation is discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim132321sciescopu

Boron-Catalyzed Silylative Reduction of Nitriles in Accessing Primary Amines and Imines

Silylative reduction of nitriles was studied under transition metal-free conditions by using B­(C₆F₅)₃ as a catalyst with hydrosilanes as a reductant. Alkyl and (hetero)­aryl nitriles were efficiently converted to primary amines or imines under mild conditions. The choice of silanes was found to determine the selectivity: while a full reduction of nitriles was highly facile, the use of sterically bulky silanes allowed for the partial reduction leading to <i>N</i>-silylimines

Boron-Catalyzed Silylative Reduction of Quinolines: Selective sp³ C–Si Bond Formation

A silylative reduction of quinolines to synthetically versatile tetrahydroquinoline molecules involving the formation of a C­(sp³)–Si bond exclusively β to nitrogen is described. Triarylborane is a highly efficient catalyst (up to 1000 turnovers), and silanes serve as both a silyl source and a reducing reagent. The present procedure is convenient to perform even on a large scale with excellent stereoselectivity. Mechanistic studies revealed that the formation of a 1,4-addition adduct is rate-limiting while the subsequent C­(sp³)–Si bond-forming step from the 1,4-adduct is facile