Directed metallations of 4-ethylidenetetronic acid O-methyl ether and its derivatives as a synthetic entry to natural 4-oxyfuran-2-ones

Abstract

Lithium di-isopropylamide removes the C-2(α-)-protons from the O-methyl tetronates (11) and (20) in a regioselective manner leading to the corresponding novel anions e.g.(18). The vinyl anions then react with a range of electrophiles providing a preparatively useful procedure for the synthesis of a range of 2-substituted O-methyl tetronates e.g. (13), (15), (16), (22), and (25). Alkylation of the vinyl anion (18) with trimethylsilyl chloride leads to the 2-silyl derivative (26) which on treatment with lithium di-isopropylamide followed by alkylation (Mel and PhCHO) gives the product [(27) and (28)] resulting from addition at C-4 in (11). Acylation of the anion derived from (26) under different reaction conditions, produces either the 4-acetoxy derivative (29) or the furan enol acetate (30). The 2′-substituted carbinol (34) is produced when the enolate derived from (26) is quenched with n-propanal.

The directed metallations of (11) and its derivatives provide access to a range of 4-oxyfuran-2-one analogues found amongst natural products.

Treatment of (11) with N-bromosuccinimide followed by triphenylphosphine produces the corresponding phosphonium salt (37b) which reacts with benzaldehyde and isovaleraldehyde to give the polyene O-methyl tetronates (38) and (39) respectively.