Regio- and Stereoselective Rhodium(II)-Catalyzed C–H Functionalization of Cyclobutanes

Abstract

Recent developments in controlled C-H functionalization transformations continue to inspire new retrosynthetic disconnections. One tactic in C-H functionalization is the intermolecular C-H insertion reaction of rhodium-bound carbenes. These intermediates can undergo highly selective transformations through the modulation of the ligand framework of the rhodium catalyst. This work describes our continued efforts toward differentiating C-H bonds in the same molecule by judicious catalyst choice. Substituted cyclobutanes that exist as a mixture of interconverting conformers and possess neighboring C-H bonds within a highly strained framework are the targets herein for challenging the current suite of catalysts. Although most C-H functionalization tactics focus on generating 1,2-disubstituted cyclobutanes via substratecontrolled directing-group methods, the regiodivergent methods discussed in this paper provide access to chiral 1,1-disubstituted and cis-1,3-disubstituted cyclobutanes simply by changing the catalyst identity, thus permitting entry to novel chemical space.

Rhodium(II)‐Catalyzed C(sp3)−H Diamination of Arylcyclobutanes

“…In fact, for arylcyclobutanes without the directing group, direct sp 3 C−H insertion using a metallocarbene or metallonitrene would be the ideal strategy to achieve cyclobutane functionalization. Davies [9] has reported successful selective direct sp 3 −sp 3 C−C bond formation in arylcyclobutanes by the classical rhodium(II)‐catalyzed carbene insertion reaction. Owing to the configuration of arylcyclobutanes, [10] and the sterically demanding and electrophilic characteristics of rhodium carbene, C−H insertion enables the activation of C−H bonds at the C‐1 and C‐3 positions of cyclobutanes but not at the neighboring positions of the substituted aryl groups (Scheme 1b).…”

Comparison of 1,2-Diarylcyclopropanecarboxylates with 1,2,2-Triarylcyclopropanecarboxylates as Chiral Ligands for Dirhodium-Catalyzed Cyclopropanation and C–H Functionalization

“…These were prepared using either Rh 2 (OOct) 4 and Rh 2 (OAc) 4 or a 1:1 mixture of both enantiomers of the indicated chiral catalyst. The following previously prepared compounds were prepared by literature procedures: dirhodium tetrakis [1-[[4-dodecylphenyl]sulfonyl](2S)-prolinate] [Rh 2 (S-DOSP) 4 ] (1), 29 dirhodium tetrakis ((S)-1,2,2-triphenylcyclopropanecarboxylate) [Rh 2 (S-TPCP) 4 ] (2a), 35 dirhodium tetrakis 33 and methyl 2-(4bromophenyl)-3-methyl-3-(p-tolyl)butanoate (26). 33 Ligand Synthesis.…”

“… They are sterically demanding catalysts capable of overcoming the natural electronic tendency of the carbenes to insert into tertiary C–H bonds, and by appropriate modifications, they can be tuned to select specific primary or secondary , C–H bond. Some of the most significant Rh-TPCP catalysts developed to date are 2a–2e , and they have been shown to be effective chiral catalysts in a range of carbene transformations. − …”

Photocatalytic three-component asymmetric sulfonylation via direct C(sp3)-H functionalization

“…Methods to control site-selectivity towards C-H bonds at the specific positions of unactivated cycloalkanes or alkanes (without the assistance of any directing group) 17 – 30 , at the same time combine with asymmetric catalysis, provide appealing opportunities for the construction of high value-added chiral molecules, but remains a remarkable challenge 31 . In this context, rhodium-carbene-induced C–H insertion has emerged as an elegant strategy for alkylation of primary, secondary, ternary alkanes, and cycloalkanes, in which chiral dirhodium catalysts with well-designed and tailored ligands are employed for both site recognition and asymmetric induction 32 – 37 .…”