Synthesis of spirocycles via ring closing metathesis of heterocycles carrying gem-diallyl substituents obtained via ring opening of (halomethyl)cyclopropanes with allyltributyltin

Abstract

In the presence of allyl tri-n-butyltin--AIBN, cyclopropylmethyl bromides/xanthates undergo ring-opening reaction with concomitant formation of geminal diallyl derivatives in good yields. The ring closing metathesis reactions on geminal diallyl derivatives with Grubbs' catalyst provided spirocyclopentenyl products. Combination of these two methodologies has been applied to the synthesis of mono-, bis-cyclopentyl-carbohydrates as well as spirocyclopentylproline derivatives.

Opportunities for the Application and Advancement of the Corey–Chaykovsky Cyclopropanation

“…For oxygen protecting groups, many have solid precedent under these cyclopropanation conditions (Scheme ). Benzyl- and para -methoxybenzyl (PMB)-protected alcohols, both for aliphatic and aromatic alcohols, have been demonstrated to give moderate to high yields (Scheme , eqs 1 and 2). , Silyl protecting groups such as tert -butyldimethylsilyl (TBS) and the more hindered tert -butyldiphenylsilyl (TBDPS) have been shown to give high yields (Scheme , eq 3, and Scheme , eq 1) . Methyoxymethyl (MOM) protecting groups have been explored in the context of both alcohol and carboxylic acid protection (Scheme , eqs 4 and 5). , …”

Large‐Ring Carbocycles

“…65 Majumdar and co-workers employed an olefin metathesis strategy in their synthesis of several spironaphthyridinone derivatives. 66 Spironaphthyridinones are a class of compounds that have shown promise in the treatment of autoimmune and other immune disorders.…”

“…Taxane Skeleton (Inouye, 1985;65 Winkler, 1989 66 ) A system analogous to the taxanes has been prepared by using the intramolecular de Mayo reaction of vinylogous esters. Irradiation of the mixture of diastereomers 223 results in cycloaddition of one diastereomer to give adduct 225 and recovery of the other isomer 224.…”

Allyltributylstannane

“…The radical-mediated cyclopropyl scission of the spirocyclopropyl bromide with allyltributylstannane in the presence of AIBN led to the formation of a gem-diallyl derivative (eq 56). 123 A facile radical cyclization-fragmentation reaction of an ω-bromoalkyl spirocyclobutanone with allyltributylstannane is known (eq 57 …”