beta-Acryloyloxysulfonyl tethers for intramolecular Diels-Alder cycloaddition reactions.

摘要

A new straightforward route to various b-hydroxy sulfones was developed, proceeding via opening of ethylene oxide or propylene oxide with readily accessible zinc sulfinates under essentially neutral aqueous conditions. Good isolated yields (63-78%) and excellent regioselectivites were observed in all cases. Opening of epoxides with zinc 1,3-butadienyl sulfinate afforded (E)-butadienyl b-hydroxyalkyl sulfones bearing b-H and b-methyl substituents in 30% yield. (E)-Butadienyl b-hydroxyalkyl sulfones bearing b-phenyl and b-tert-butyl substituents were successfully synthesized in high yields from butadiene sulfone by coupling of silyl (Z)-butadienyl sulfinate with the corresponding a-bromo ketone, reduction of the resulting product to the secondary alcohol and DMAP-induced (Z)/(E)-isomerization. The esterification of synthesized (E)-butadienyl b-hydroxyalkyl sulfones provided a series of b-acryloyloxy sulfones that differed in the bulk of the substituent on the sulfone tether (H, Me, Ph and tert-Bu) and also in the substitution on the acrylate ester residue (methacrylate, acrylate, a-bromoacrylate and crotonate esters), thus providing a variety of possibilities for Diels-Alder studies. Thermally-mediated intramolecular Diels-Alder cycloaddition reactions of these newly synthesized b-acryloyloxy sulfones proceeded with complete regioselectivity, high (10/1) to complete endo/exo-selectivity, and resulted in the preferential formation of one of the two possible endo-cycloadducts. The yields and stereoselectivities were proportional to the bulk of the substituent on the b-acyloxysulfonyl tether. The proclivity toward Diels Alder reaction increased in the order: acrylates methacrylates a-bromoacrylates. In the case of R1 = tert-butyl, the major endo-cycloadducts were separated in 71-72% yield. The computational study conducted suggested that the Diels-Alder reaction proceeds as an asynchronous concerted process; no net loss of electron density from the butadienyl fragment to the acrylate dienophile is observed in the TS. The methacrylate Diels-Alder cycloadduct, available in good yield as a single diastereomer via the developed chemistry, was converted to the corresponding a,b-unsaturated ketone which on reaction with isoprene underwent a highly unusual hetero-Diels-Alder reaction at the ketone C=O group to afford a single spiro-diastereomer. To the best of our knowledge, this is the first example of a hetero-Diels-Alder reaction when both the ketone and diene are unactivated.