Utilization of Borane-Catalyzed Hydrosilylation as a Dearomatizing Tool: Six-Membered Cyclic Amidine Synthesis from Isoquinolines and Pyridines

Abstract

In this study, a convenient strategy to synthesize six-membered­ cyclic amidines from isoquinolines and pyridines has been developed. Borane-catalyzed hydrosilylation of each N-heteroarene was utilized as a dearomatizing tool. Substrate scope is broad with respect to both isoquinolines and pyridines, with various reaction pathways depending on the substitution pattern of the N-heteroarenes. The reaction mechanism and reactivity of each class of N-heteroarenes has been discussed. The resulting six-membered (Z)-sulfonyl amidine products are rarely reported and are mostly unprecedented. The scalability of this method and versatility of the cyclic amidine products are also presented.

Synthesis of Cyclic N-Acyl Amidines by [3 + 2] Cycloaddition of N-Silyl Enamines and Activated Acyl Azides

“…The reactivity of N -silyl enamine from isoquinoline 1a was found to be promising; thus, we began our study with isoquinoline [ 15 ]. Using the previously optimized conditions for the dearomative mono-hydrosilylation of 1a , we obtained the N -silyl enamine intermediate with good yield in a nuclear magnetic resonance (NMR) cell.…”

“…Thus, several research groups have been developing synthetic methodologies for these derivatives [ 12 , 13 ]. Although most precedent pathways use cyclic amides as starting materials [ 11 , 12 , 13 ], our group recently reported a novel synthetic strategy that uses the readily available N -heteroarenes as starting materials and proceeds via a versatile N -silyl enamine intermediate ( Scheme 1 a) [ 14 , 15 ]. We achieved this intermediate through the B(C 6 F 5 ) 3 catalyzed dearomative hydrosilylation of N -heteroarene, which is considered an emerging area in organic synthesis [ 16 , 17 , 18 , 19 ].…”

“…However, reports on the reactivity of N -silyl enamine are relatively rare, which is most likely due to the intrinsic instability of its N-Si bond at ambient conditions [ 22 , 23 ]. Nevertheless, the in situ use of N -silyl enamine is still an attractive strategy, in which the silyl group is used as the transient protecting group for the fragile but useful free enamine for organic synthesis [ 14 , 15 ].…”

“…Our previous works demonstrated [ 14 , 15 ] the wide substrate scope of N -heteroarenes; however, the scope of organic azides has been mainly limited to sulfonyl azides. Sulfonyl azides exhibit powerful reactivity; however, their reaction with acyl azides to synthesize the desired acyl amidine product has not yet been realized ( Scheme 1 b) [ 14 ].…”

“…Sulfonyl azides exhibit powerful reactivity; however, their reaction with acyl azides to synthesize the desired acyl amidine product has not yet been realized ( Scheme 1 b) [ 14 ]. Interestingly, we recently found that the electron-withdrawing groups of sulfonyl azides increased the reactivity of the cycloaddition reaction [ 15 ]. This prompted us to develop a [3 + 2] cycloaddition reaction that uses the electron-withdrawing group on the less reactive acyl azides ( Scheme 1 c).…”