Stereoselective synthesis of alkyl-, aryl-, vinyl- and alkynyl-substituted Z-enamides and enol ethers

Abstract

Highly stereoselective synthesis of Z-enamides and enol ethers at room temperature via an umpolung/cross coupling strategy applicable to drugs and natural products.

Stereocontrolled Synthesis of Halovinylbenziodoxoles by Hydro‐ and Iodochlorination of Ethynylbenziodoxoles

“…Miyake reported anti ‐addition of phenols to aryl‐EBXs under visible‐light irradiation (Scheme b), in which the primary VBX product readily transforms into iodovinylether . More recently, Waser has found simple conditions that allow for the anti ‐addition of sulfonamides and phenols to alkyl‐EBXs with retention of the BX moiety in the products . As highly functionalized VBX compounds hold promise as versatile synthetic building blocks for stereodefined alkenes, further development of EBX‐to‐VBX transformations is highly desirable.…”

“…Scheme illustrates proposed reaction pathways for the present hydrochlorination and iodochlorination reactions. The hydrochlorination may proceed through β‐addition of a chloride ion to EBX and subsequent protonation of the resulting vinyl anion by a pyridinium proton (Scheme a) . Preliminary DFT calculations on a model system (B3LYP/SDD for I, 6‐31+G(d) for other atoms) allowed us to locate a transition state of chloride addition ( TS1 ), which adopts a substantially bent structure and leads to a vinyl anion CP1 (see the Supporting Information for more detail).…”

“…[8] More recently,W aser has found simple conditions that allow fort he anti-addition of sulfonamides and phenolst oa lkyl-EBXs with retention of the BX moiety in the products. [9,10] As highly functionalized VBX compounds hold promise as versatile synthetic building blocks for stereodefined alkenes, [11] furtherd evelopment of EBX-to-VBX transformations is highly desirable.Herein, we report on stereoselective hydrochlorination and iodochlorination reactions of EBX, affording stereochemically well-defined halogenated VBX compounds (Scheme1c). The formerr eactionw as achievedu sing pyridineh ydrochloride in an exclusive anti-fashion, affording au seful buildingb lock for the stereoselective synthesiso fm ultisubstituted alkenes.…”

“…[8] More recently,W aser has found simple conditions that allow fort he anti-addition of sulfonamides and phenolst oa lkyl-EBXs with retention of the BX moiety in the products. [9,10] As highly functionalized VBX compounds hold promise as versatile synthetic building blocks for stereodefined alkenes, [11] furtherd evelopment of EBX-to-VBX transformations is highly desirable.…”

“…The hydrochlorination may proceed through b-addition of ac hloride ion to EBX and subsequentp rotonation of the resulting vinyl anionb yapyridinium proton (Scheme 2a). [9,14,15] Preliminary DFTcalculations on am odel system (B3LYP/SDD for I, 6-31 + G(d) for othera toms)a llowedu st ol ocate at ransition state of chloride addition (TS1), which adopts as ubstantially bent structure and leads to avinyl anion CP1 (see the Supporting Information for more detail). CP1 has cis arrangement of the Cl and BX groups,a nd its protonation would afford the anti-hydrochlorination product.…”