Borane‐Catalyzed Synthesis of Quinolines Bearing Tetrasubstituted Stereocenters by Hydride Abstraction‐Induced Electrocyclization

Abstract

The borane-catalyzed synthesis of quinoline derivatives bearing tetrasubstituted stereocenters from vinyl anilines has been developed. Mechanistic studies and quantum-mechanical investigations support the hydride abstraction/electrocyclization/hydride addition mechanism. The products were obtained in up to 99 % yield with a diastereoselectivity of >99 % in favour for the 3a-5-cis isomer.

Electron deficient borane-mediated hydride abstraction in amines: stoichiometric and catalytic processes

“…Borane-mediated hydride abstraction has also been used in the synthesis of tetrahydroquinolines by the research groups of Grimme and Paradies, 38 and Wang 39 (Schemes 27 and 28, respectively). In both cases, B(C 6 F 5 ) 3 -catalysed the efficient conversion of 2-amino styrenes 138 and 145 into tetrahydroquinolines 139 and 146.…”

Divergent Synthesis of N‐Heterocycles by Merging Borane‐Mediated Cyclopropane Ring‐Opening and Hydride Abstraction

“…In the presence of B(C 6 F 5 ) 3 (20 mol%), reacting 1a in toluene at 150 °C for 24 h gave cyclopropane‐fused tetrahydroquinoline 2a and vinyl‐substituted indoline 3a in 16% and 6% yields, respectively (Table 1, entry 1). In our previous works, Lewis acidic additives ( e.g ., TMSOTf) were found to accelerate B(C 6 F 5 ) 3 ‐catalyzed cyclization of 2‐vinyl‐ N , N ‐ dialkylanilines by facilitating the hydride delivery, [ 8b ] and Lewis basic additives ( e.g ., 2,6‐dibromopyridine) were found to improve B(C 6 F 5 ) 3 ‐catalyzed isomerization of cyclopropanes by stabilizing the carbocation. [ 5b ] Therefore, we screened a number of Lewis acids and Lewis bases as additives.…”

“…TMSOTf might function as a transient hydride acceptor to facilitate the catalytic turnover. [ 8b ] Since the electron‐donating alkoxy group played a key role in favoring the formation of 2 , an alternative pathway involving the alkoxy group is proposed (Scheme 5b). In this pathway, the cyclization is promoted by the electron‐rich aryl ring by conjugation; subsequent elimination of B(C 6 F 5 ) 3 gave the final product.…”

“…Another interesting activity of B(C 6 F 5 ) 3 is the abstraction of a hydride from an N ‐alkyl group to form an ion pair of an iminium and a borohydride (Scheme 1b). [ 6 ] Recently, a number of B(C 6 F 5 ) 3 ‐catalyzed dehydrogenation, [ 7 ] cyclization, [ 8 ] and addition reactions [ 9‐10 ] were developed by utilizing this activity. Because of our ongoing interest on borane catalysis, [ 11 ] we questioned whether it is possible to develop new reactions by merging B(C 6 F 5 ) 3 ‐mediated cyclopropane ring‐opening and hydride abstraction.…”

Silver/Rhodium Relay Catalysis Enables C−H Functionalization of In Situ Generated Isoquinolines with Sulfoxonium Ylides: Construction of Hexahydrodibenzo[a,g]quinolizine Scaffolds

“…[2] Moreover, tetrahydroprotoberberine alkaloids such as STY containing azapolycyclic motif can selectively bind with G-quadruplex DNA, which has been often studied as a target for anti-cancer drug (Figure 1). [3] In recent decades, numerous methods have been developed to construct similar structural motifs, [4] however, those methods usually suffer from complicated multistep operations. Thus, it is highly desirable to develop a creative synthetic route that enables facile preparation of a wide range of such polyheterocyclic derivatives.…”