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.T he Z-selectivity of the reaction is jointly controlled by the kinetics of the diastereoselective MBH addition and cis-selective Pc-elimination elimination. [15] To our delight, the method followed by hydrolysis of oxazolines could be used for gram-scale synthesis of a-aryl a,b-unsaturated carboxylic acids 8a and 8b with synthetically useful yields (Scheme 4A). Ther emaining iodide atom allowed for elaborating alkenes with ab oryl group ( 9)o r vinyl ester moieties (10 a and 10 b), and incorporating an alkynyl group into phenyl ring (11 a and 11 b)( Scheme 4B).…”

“…[13] 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.A s ar esult, the MBH-type rearrangement of aryl sulfoxides enables Z-selective a-CÀHa rylation of a,b-unsaturated nitriles as we disclosed recently (Scheme 1B). [15] In contrast with the established Z-selectivity,w eh erein describe an E-selective MBH-type rearrangement by employing an ew pair of rearrangement partners consisting of aryl iodanes and a,b-unsaturated oxazolines (Scheme 1C).…”

“…[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.A s ar esult, the MBH-type rearrangement of aryl sulfoxides enables Z-selective a-CÀHa rylation of a,b-unsaturated nitriles as we disclosed recently (Scheme 1B). [15] In contrast with the established Z-selectivity,w eh erein describe an E-selective MBH-type rearrangement by employing an ew pair of rearrangement partners consisting of aryl iodanes and a,b-unsaturated oxazolines (Scheme 1C). Henceforth, with these two MBH-type rearrangements in hand, both E-and Za-aryl a,b-unsaturated carbonyl derivatives can now be accessed on demand by switching to aproper rearrangement partners.Inthis Article,wealso describe mechanistic studies towards understanding the intriguing opposite stereoselectivities associated with such two MBH-type rearrangement reactions.…”