Stereo‐ and regioselective intramolecular heck reaction of α‐amino acid derivatives for the synthesis of enantiopure 3,4‐dihydroisoquinolinones

Abstract

Acylation of the alkenes la-d and 3, easily prepared from the corresponding a-amino acids, with 2-iodobenzoyl chloride gives 2a-d and 4 which cyclize to the enantiopure dihy-droisoquinolinones 5a-d and 9, resp., in an intramolecular Heck reaction using 5 mol-% of Pd(OAc), in the presence of PPh3, TPAB, and KOAc with excellent diastereoselectivity.

Synthesis of Heterocycles via Palladium-Catalyzed Oxidative Addition

“…In a similar manner, chiral benzamides have been used to obtain 3,4-dihydroisoquinolinones (Scheme 37). 37 The reaction of benzamide 83 carried out in the presence of catalytic Pd(OAc) 2 /PPh 3 and tetrapropylammonium bromide (TPAB) in DMF afforded a mixture of isoquinolinones 84 and 85 in 66-82% yields with high diastereo-and regioselectivity. The selectivity increases with increasing bulk of the substituent at the stereogenic center.…”

Enantioselective Palladium-Catalyzed Transformations

“…The general outlines of the mechanism of the Heck reaction , and the factors governing the regio- and enantiocontrol of the reaction have been discussed in several reviews. 17a-e Because of the major limitation that the Heck reaction displays low regioselectivity in the double bond formation step, all the reported enantioselective Heck reactions leading to the formation of tertiary centers have been done on cyclic alkenes, with the exception of Tietze's allylsilane-terminated enantioselective Heck reaction (vide infra) . Using cyclic alkenes in the Heck reaction, the syn elimination of HPdL 2 from the first formed syn adduct can only take place in one direction since the otherwise necessary σ-bond rotation is not possible in cyclic alkenes (Scheme ).…”