Direct Access to 9/6‐Fused Cycles via Sequential Hydride Shift Mediated Double C(sp³)−H Bond Functionalization

Abstract

We have developed a sequential hydride shift process involving a [1,8]‐hydride shift. When cinnamylidene malonates having a biphenyl core were treated with 30 mol% Yb(OTf)3 and 10 mol% iPr2NEt, the desired sequential [1,8]‐[1,5]‐hydride shift process proceeded smoothly to afford synthetically challenging nine‐membered carbocycle‐fused piperidine derivatives in good chemical yields (up to 77%). Notably, the desired nine‐membered carbocycles could not be obtained by a single [1,8]‐hydride shift/cyclization process, suggesting that the employment of the sequential system is crucial to achieving the reaction.

Silyl-Group Boosted Internal Redox Reaction: Hydride Shift from an Aliphatic Secondary Position for the Formation of Six- and Seven-Membered Carbocycles

“…Many transition metal catalyst aided transformations involving the functionalization of not only the C­(sp 2 )–H bond but also the C­(sp 3 )–H bond, the most inert C–H bond, have been developed . Recently, the hydride shift triggered C­(sp 3 )–H bond functionalization, namely, the internal redox reaction, has been the focus of much interest because of the following features (upper part of Figure ): (1) no requirement of transition metal catalysts and external oxidants, (2) transformation of C­(sp 3 )–H bond, and (3) construction of various fused-cycles. − Because the electronic assistance of the adjacent position is important for the smooth progress of the hydride shift process, most of the reported reactions focus on the functionalization of C–H bond α to a heteroatom. Corresponding reactions on positions without an adjacent heteroatom are limited, and the benzylic position that can receive electronic assistance from π-electrons of the aromatic ring is the only choice. − ,, Not surprisingly, there were no examples of the hydride shift from aliphatic positions until our work in 2011, where we reported the hydride shift from the simple aliphatic tertiary position (methine group) by using benzylidene barbituric acid as the electrophilic portion .…”

Synthesis of Polysubstituted Naphthalenes by a Hydride Shift Mediated C–H Bond Functionalization/Aromatization Sequence

“…These reactions, however, have one problematic point: the narrow potential for transformation from the adducts. To broaden the synthetic potential of internal redox reaction, we have concentrated on the reaction of substrates having a linker between the aromatic ring and the heteroatom in recent years, , the products of which are compounds with a heteroatom exo to the cyclic structure, which functions as a handle for further transformation. Based on this strategy, transformations including the double C­(sp 3 )–H bond functionalization and the sequential system involving the C­(sp 3 )–H bond functionalization/Friedel–Crafts reaction have been developed.…”

“…To broaden the synthetic potential of internal redox reaction, we have concentrated on the reaction of substrates having a linker between the aromatic ring and the heteroatom in recent years, , the products of which are compounds with a heteroatom exo to the cyclic structure, which functions as a handle for further transformation. Based on this strategy, transformations including the double C­(sp 3 )–H bond functionalization and the sequential system involving the C­(sp 3 )–H bond functionalization/Friedel–Crafts reaction have been developed. Herein we report a new entry in related chemistry: C­(sp 3 )–H bond functionalization/aromatization sequence for the synthesis of polyaromatic compounds …”

Divergent synthesis of multi-substituted phenanthrenes via an internal redox reaction/ring expansion sequence

“…1 Because of its useful features such as transformation of the most inert C–H bond, C(sp 3 )–H bond, and no need of transition metal catalysts and external oxidants, many research groups have concentrated on this chemistry and various useful organic transformations have been developed (Scheme 1). 2–6…”