Inter-and intramolecular (4+3) cycloadditions of epoxy allylsilanes as dienophiles

Abstract

The synthesis of methylenated bicyclic cycloadducts was achieved by formal (4+3) cycloadditions of epoxy allylsilanes with different dienes. The epoxy allylsilane functions as a dienophile in this (4+3) cycloaddition reaction. The oxirane in the epoxy allylsilane, once activated by a Lewis acid, serves as a good dienophile while the allylsilane moiety completes the construction of the cycloadducts through the desilylation of the (trimethylsilyl)methyl group.

Epoxy allylsilane reacts with furan, 2,5-dimethylfuran, and cyclopentadiene in the presence of a catalytic amount of TESOTf to afford the intermolecular (4+3) cycloadducts in moderate yields and without diastereoselectivity.

The epoxy allylsilanes tethered to a diene were also synthesized to study the intramolecular reaction. Reaction with TESOTf results in the formation of the intramolecular cycloadducts with 5,7- and 6,7-fused bicyclic frameworks in moderate to good yields. Generally, due to the absence of a polar residue and a dipole moment, both endo and exo cycloadducts are formed in the cycloaddition reaction. However, the diastereoselectivity of the cycloaddition can be controlled by steric elements. The intramolecular cycloaddition is diastereoselective when R3 bears a substituent, providing only the exo cycloadduct.

Experiments with the optically pure epoxy allylsilane (+)-3.2s show that the reaction proceeds by the diene attacking the backside of the activated epoxide, allowing the synthesis of enantiomerically enriched cycloadducts.

This study represents the widest scope of allylsilanes substrates (21 examples) engaging in (4+3) cycloadditions to date.

An operationally simple and mild Peterson olefination protocol is facilitated by the use of copper (II) chloride dihydrate to promote the acid-promoted dehydrative desilylation reaction. Various β-hydroxysilanes have been converted to olefins in yields of up to 97%. The copper (II) chloride dihydrate acts as an easily handled and inexpensive precursor of Brønsted acid that promotes the elimination, yielding alkenes. Many acid-sensitive compounds are obtained in higher yields and are stable under these conditions in which a low and controlled amount of Brønsted acid is produced in situ.