Z‐Selective α‐Arylation of α,β‐Unsaturated Nitriles via [3,3]‐Sigmatropic Rearrangement

Abstract

The Morita‐Baylis–Hillman (MBH) reaction and [3, 3]‐sigmatropic rearrangement are two paradigms in organic synthesis. We have merged the two types of reactions to achieve [3,3]‐rearrangement of aryl sulfoxides with α,β‐unsaturated nitriles. The reaction was achieved by sequentially treating both coupling partners with electrophilic activator (Tf2O) and base, offering an effective approach to prepare synthetically versatile α‐aryl α,β‐unsaturated nitriles with Z‐selectivity through direct α‐C‐H arylation of unmodified α,β‐unsaturated nitriles. The control experiments and DFT calculations support a four‐stage reaction sequence, including the assembly of Tf2O activated aryl sulfoxide with α,β‐unsaturated nitrile, MBH‐like Lewis base addition, [3,3]‐rearrangement, and E1cB‐elimination. Among these stages, the Lewis base addition is diastereoselective and E1cB‐elimination is cis‐selective, which could account for the remarkable Z‐selectivity of the reaction.

Morita–Baylis–Hillman‐Type [3,3]‐Rearrangement: Switching fromZ‐ toE‐Selective α‐Arylation by New Rearrangement Partners

“…In contrast, the E1cb‐elimination in the reaction of aryl sulfoxides is prompted by K 2 CO 3 and is irreversible. The Z ‐selectivity of the reaction is jointly controlled by the kinetics of the diastereoselective MBH addition and cis‐selective Pc‐elimination elimination [15] …”

“…Recently, the stepwise strategy continued to illuminate us to merge Morita–Baylis–Hillman (MBH) reaction with the rearrangement chemistry [14, 15] . As depicted in Scheme 1, the addition/elimination of MBH process could be merged with the rearrangement of aryl sulfoxides and aryl iodanes.…”

“…As a result, the MBH‐type rearrangement of aryl sulfoxides enables Z‐selective α‐C−H arylation of α,β‐unsaturated nitriles as we disclosed recently (Scheme 1 B). [15] In contrast with the established Z ‐selectivity, we herein describe an E ‐selective MBH‐type rearrangement by employing a new pair of rearrangement partners consisting of aryl iodanes and α,β‐unsaturated oxazolines (Scheme 1 C). Henceforth, with these two MBH‐type rearrangements in hand, both E‐ and Z ‐α‐aryl α,β‐unsaturated carbonyl derivatives can now be accessed on demand by switching to a proper rearrangement partners.…”

Morita-Baylis-Hillman Type [3,3]-σ Rearrangment Enabled Z-Selective α-Arylation

“…该反应广为接受的机理包括四个步 骤, Michael 加成、Aldol 加成、分子内质子转移和最终 的 β-消除 [7][8][9] (Scheme 1b). 近日, 彭勃课题组与中国科 学院大学化学与化学工程学院汪志祥课题组 [10]…”

Revisiting Aromatic Claisen Rearrangement Using Unstable Aryl Sulfonium/Iodonium Species: The Strategy of Breaking Up the Whole into Parts

“… Further studies of the discovery led us to recognize two critical strategies that did not exist in traditional Claisen rearrangement but could serve as a guide for the development of this nontraditional rearrangement. One strategy is the division of the conventional one-step construction of rearrangement precursors into two or more steps that allows us to control each step of the reaction more precisely, thus not only expanding the substrate scope but also inspiring the development of [5,5]-sulfonium rearrangement, asymmetric iodonium rearrangement, and Morita–Baylis–Hillman (MBH)-type sulfonium/iodonium rearrangements. , The other strategy is the use of the effect of congestion-accelerated rearrangement for developing the rapid ketenimine-iodonium Claisen rearrangement, which further led to the first examples of the dearomatization of aryl iodanes . In this Account, we will provide an overview of these rearrangement reactions developed in our laboratory and will try to illustrate our logic behind these designs.…”