Diastereoselective Synthesis of trans‐1,2‐Dialkylcyclopropanols by the Kulinkovich Hydroxycyclopropanation of Homoallylic Alcohols.

Abstract

-052Diastereoselective Synthesis of trans-1,2-Dialkylcyclopropanols by the Kulinkovich Hydroxycyclopropanation of Homoallylic Alcohols.-Title compounds are prepared in an enantio-and diastereoselective manner via bicyclic titanacyclopropane intermediates.

Modern applications of low-valent early transition metals in synthesis and catalysis

“…Since these initial reports, several improvements have been made to this chemistry. Intermolecular alkene couplings can be achieved by using cyclohexyl or cyclopentylmagnesium chloride to activate Ti(O i Pr) 4 , as the resulting Ti-cyclopentene (or cyclohexene) adduct 9 can be displaced by monosubstituted or tethered alkenes to make a new alkene adduct 10 (REFS 99 , 100 ) (FIG. 3a, bottom).…”

“…The Kulinkovich cyclopropanation has an intrinsic diastereoselectivity for the cis-1,2-dialkylated cyclopropanol when using Grignard reagents larger than ethyl, and the use of chiral TADDOL (a,a,a’,a’-tetraaryl-2,2-disubstituted-1,3-dioxolane-4,5-dimethanol) ligands has allowed for good enantioselectivity 88,101,102 . This diastereoselectivity can be reversed when cyclopropanating homoallylic alcohols as a result of coordinating directing group effects 99 or remote stereocentre influences 103 .…”

Ti-Catalyzed Diastereoselective Cyclopropanation of Carboxylic Derivatives with Terminal Olefins

“…The Kulinkovich reaction, first reported in 1989, converts carboxylic esters to 1,2-disubstituted cyclopropanols in the presence of alkyl Grignard reagents and a stoichiometric titanium alkoxide . Then, this reaction received considerable attention and substantial progress has been achieved in terms of its variants, including the catalytic version, cyclopropanation of carboxamides , or nitriles, and Zr-mediated cyclopropanations, − using olefins as reaction partners. − However, the direct catalytic cyclopropanation of carboxylic acids has remained unexplored. Among most of these reports, stoichiometric amounts of alkyl Grignard reagents were essentially used, largely limiting the functional group compatibility and usually requiring high Ti loading and syringe pump addition to inhibit the direct nucleophilic attack to the carbonyl group (Figure b).…”

Catalytic Hydroxycyclopropanol Ring-Opening Carbonylative Lactonization to Fused Bicyclic Lactones

“…To achieve this goal, cyclopropanols such as 6 would be required. They can be convergently assembled from readily available ester 7 and homoallylic alcohol 8 using the cyclopropanol synthesis protocol developed by Cha and co-workers . We envisioned a process involving Pd-catalyzed β-carbon elimination to generate Pd-homoenolate 9 .…”

“…Our investigation started with known hydroxycyclopropanol 15a (Table ). When it was subjected to the carbonylative spirolactonization conditions we developed before with ([Pd­(neoc)­(OAc)] 2 (OTf) 2 as the catalyst and 1,4-benzoquinone (BQ) as the oxidant, the formation of 16a was not observed (entry 1). Switching [Pd­(neoc)­(OAc)] 2 (OTf) 2 to palladium­(II) trifluoroacetate (Pd­(TFA) 2 ) was not fruitful either (entry 2).…”