Carbon-carbon bond formation by ‘double activation’. The synthesis of piperolide and fadyenolide intermediates.

Synthetic routes to the piperolides, fadyenolides, epoxypiperolides, and related compounds

“…A very similar methodology has recently been used for the production of 4-alkoxy-3,4-dihydropyrrol-2-0nes.~~ required methoxy compounds, and that was with tetramethyl orthocarbonate, when the ester (46) was produced in 81% yield even on anhydrous work-up. Furthermore, zinc bromidecatalysed reaction of compound (24) with methyl orthoformate gave acetal (45) in 92% yield, and of compound (24) with tetramethyl orthocarbonate gave ester (46). Elimination of methanol from acetal (45) proved troublesome, but low-temperature reaction with t-butyl-lithium gave compound (21) in 82% yield.…”

“…This shows that the Lewis acid-catalysed reactions of compound (24) 3 1 *32 with orthocarbonates, orthoesters, acetals, ketones, and aldehydes proceed with great efficiency at low temperatures. Catalytic quantities of titanium tetrachloride or zinc bromide, or stoicheiometric amounts of trifluoroboranediethyl ether, may be used, but use of tetrabutylammonium fluoride simply led to extensive and rapid decomposion of compound (24).…”

“…Condensation with ketones also proceeded well, but the reaction with acetyl chloride was difficult, equimolar proportions of reactants giving rise to polymeric products. Only when compound (24) was added to a large excess of acetyl chloride was the ketone trapped as a mixture of the E-and 2-enol acetates (93).…”

“…The mixture was allowed to warm to room temperature, quenched with saturated aqueous ammonium sulphate (10 ml), and extracted with dichloromethane (3 x 50 ml), and the extract was dried (Na,SO,), filtered, and the filtrate was concentrated at waterpump pressure. Fractional distillation gave the title compound (ii) A solution of benzenesulphenyl chloride (0.15 g, 1 mmol) in dry dichloromethane (2 ml) was added slowly to a stirred solution of compound (24) in dichloromethane (4 ml) at -78 "C under nitrogen. The solution was stirred at room temperature for 24 h, and the crude product (0.23 g) was purified by p.1.c.…”

Chemoselective S-benzylation of indoline-2-thiones using benzyl alcohols

“…[12][13][14][15][16][17][18][19] In 1974, Jain et al had reported BF 3 etherate-promoted C-prenylation of the phloroglucinol nucleus. 20 Subsequently, BF 3 etherate complex was shown to catalyze C-benzylation of aromatic systems using benzyl alcohols.…”