Protecting groups for the pyrrole nitrogen atom. The 2-chloroethyl, 2-phenylsulfonylethyl, and related moieties

Abstract

The 2-chloroethyl and 2-phenylsulfonylethyl moieties are versatile protecting groups for the pyrrole nitrogen atom. The 2-chloroethyl group is easily attached under phase transfer conditions using 1,2-dichloroethane. The 2-phenylsulfonylethyl moiety is readily appended under both phase transfer and homogeneous solution conditions using 2-phenylsulfonylcthyl chloride 5. Deprotection of the N-(2-chloroethyl)pyrroles is accomplished by means of efficient three-step, one-pot sequences via the N-vinyl compounds 3 and subsequent degradation of the N-(1-hydroxyethyl) compounds 4 or the acctoxymercuration derivatives 5 obtained therefrom. The 2-phenylsulfonylethyl group is excised by a reverse Michael reaction using sodium hydride or DBN as the base.The utility of the 2-chloroethyl protecting group is exemplified in a synthesis of benzyl cyclopenta[b] |pyrrole-5-carboxylate 13 from 1-(2-chloroethyl)-4-oxotetrahydroindolc 2d.