Overcoming O–H Insertion to Para-Selective C–H Functionalization of Free Phenols: Rh(II)/Xantphos Catalyzed Geminal Difunctionalization of Diazo Compounds

Abstract

Para-selective C–H functionalization of free phenols by metal carbenoids is rather challenging due to the generally more favorable competing O–H insertion. Herein, with the use of the combination of Rh­(II) and a Xantphos ligand as the catalyst, a novel multicomponent reaction of free phenols, diazoesters, and allylic carbonates was successfully developed, affording a wide variety of phenol derivatives, bearing an all-carbon quaternary center and a synthetically useful allylic unit. This reaction is likely to occur through a tandem process of carbene-induced para-selective C–H functionalization, followed by Rh­(II)/Xantphos-catalyzed allylation. The distinctive reactivity of para-selective C–H rather than O–H insertion for the carbenoid intermediate, combined with features of excellent functional group compatibility, high atom and step economy, and ease in further diversification of the products, might render this protocol highly attractive in facile functionalization of unprotected phenols.

Efficient Synthesis of Diaryl Quaternary Centers by Rh(II)/Xantphos Catalyzed Relay C−H Functionalization and Allylic Alkylation

“…In contrast, in the absence of Rh 2 (esp) 2 , Xantphos or Cs 2 CO 3, no or only trace amount of desired product 5 a was detected (80 % vs. 0–13 %). Based on these experimental results and literature precedents, [79,80] we proposed that this transformation is most likely to proceed via an initial C( sp 2 )−H functionalization of the aniline derivatives 2 by the Rh(II)‐carbenoid intermediate generated in situ from the catalyst and the diazoester 1 , followed by the subsequent [Rh 2 ]/Xantphos‐catalyzed allylic alkylation of 3 assisted by the base. This mechanism is distinctive from those for the well‐known [Rh(II) 2 ]‐catalyzed MCRs [10] .…”

“…[71][72][73][74] In this context, the catalytic construction of diaryl quaternary center with an allylic synthetic handle from the carbene Chemistry-A European Journal www.chemeurj.org induced CÀ H functionalization of a simple arene is highly desirable, but remains underexplored probably due to the difficulties in the combination of metal-carbene insertion process with allylic alkylation (Scheme 1a,ii). [75][76][77][78] As a continuation of our efforts in development of dirhodium(II)/Xantphos-catalyzed three-component difunction-alization of diazo compounds, [79,80] we envisioned the electrophilic allyl reagents might be ready to intercept the α, αdiarylacetate intermediate that is generated from α-diazo esters and N, N-disubstituted anilines by a dirhodium complex (Scheme 1b). Herein, we wish to report a three-component reaction of N, N-disubstituted aniline, α-diazo ester, and an allylic electrophile using a dirhodium(II)/Xantphos catalyst, furnishing various aniline derivatives with diaryl allylic quaternary centers in good yields (Scheme 1b).…”

“…As a continuation of our efforts in development of dirhodium(II)/Xantphos‐catalyzed three‐component difunctionalization of diazo compounds, [79,80] we envisioned the electrophilic allyl reagents might be ready to intercept the α , α ‐diarylacetate intermediate that is generated from α ‐diazo esters and N , N ‐disubstituted anilines by a dirhodium complex (Scheme 1b). Herein, we wish to report a three‐component reaction of N , N ‐disubstituted aniline, α ‐diazo ester, and an allylic electrophile using a dirhodium(II)/Xantphos catalyst, furnishing various aniline derivatives with diaryl allylic quaternary centers in good yields (Scheme 1b).…”

Dirhodium: carbene transformations and beyond

“…Under a similar catalytic system, a multicomponent reaction of free phenols, diazoesters and allylic carbonates could also occur, providing a wide range of phenol derivatives in 51–92% yields, at which a quaternary carbon center and a useful allylic unit are situated (Scheme 73). 122 Interestingly, a distinctive reactivity of para -selective C–H rather than O–H insertion was observed. However, the catalytic asymmetric version still remains a challenging task as the best result was only 2% ee for various combinations of Rh 2 ( ii ) and diphosphine in the preliminary attempt.…”

Forming All-Carbon Quaternary Centers by Geminal Difunctionalization of Diazo Compounds with N,N-Disubstituted Anilines and Allylic Carbonates

“…By using allylic carbonates as the reagents, Wang, Hu, and Huang have realized the three-component reactions of anilines/alcohols, diazo compounds, and allylic carbonates, which proceeds through a sequential N–H/O–H insertion and a substitution reaction (Scheme a). Just recently, Wang reported a rhodium/XantPhos-catalyzed difunctionalization of diazoacetates through a tandem Csp 2 –H insertion of phenols and allylic alkylation (Scheme b) . As a continuation of our interest, we recently focused on C–H insertion reactions of electron-rich arenes and indoles .…”