Expedient Approach to 6‐Bromo‐2‐isopropylidenecoumaranone, a Potential Intermediate for the Synthesis of TMC‐120B, Pseudodeflectusin, and Their Congeners

Abstract

A straightforward approach toward 6-bromo-2-isopropylidenecoumaranone, a potential intermediate toward alkaloid TMC 120-B, pseudodeflectusin, and other natural products, was reported. The synthetic sequence involved the reaction of 3-bromosalicylaldehyde with chloroacetone and cyclization of the resulting ether to a 2-acetylcoumaranol intermediate. This was followed by sequential methyl Grignard addition and Jones' oxidation to the corresponding coumaranone, which was dehydrated to the final product with the methanesulfonyl chloride/pyridine reagent. The protection of the coumaranol as the corresponding THP-ether resulted in improved product yields.

First total synthesis of the only known 2-isopropyliden-2H-benzofuran-3-one isolated from V. luetzelburgii

“…We have previously employed lifolinol (10), a heliantaceous 2,3-dihydrobenzofuran for the synthesis of inhibitors of the human complement cascade 20 and have synthesized a potential key intermediate toward TMC-120B (4). 21 In pursuit of our studies on naturally-occurring benzofuran derivatives, herein we report the rst total synthesis of the 2-isopropylidenebenzofuran-3-one 8 in its racemic and in one of its optically active forms, from a common intermediate and employing 4 0hydroxyacetophenone (11) as starting material.…”