Hydroxy‐Directed Cyclopropanation of Esters: Synthesis of Trisubstituted Cyclopropanols

Abstract

The Kulinkovich cyclopropanation of esters with disubstituted homoallylic alcohols is described for the preparation of 1,2,3‐trisubstituted cyclopropanols. Central to the successful implementation is the generation in situ of a temporary alkoxy tether between a homoallylic alcohol and an alkoxytitanium species to override unfavorable steric factors.

Cyclopropene Derivatives as Precursors to Enantioenriched Cyclopropanols and n‐Butenals Possessing Quaternary Carbon Stereocenters

“…[22] Having established an easy protocol for the preparation of either 4 or 5 from simple starting materials, the enantioselective synthesis of the cyclopropenylmethyl ether 1d and cyclopropenylmethyl ester 1l were easily achieved in high enantiomeric ratio (e.r. 93:7) through cyclopropenation of the terminal alkyne with methyl phenyldiazoacetate and [Rh 2 (S-DOSP) 4 ]a st he catalyst (Scheme 3). [23] Thec ombined diastereoselective carbometalation reaction followed by selective oxidation of 1dproceeds to give the enantiomerically enriched cyclopropanols 4h,i as as ingle diastereoisomer with the same enantiomeric ratio as the starting material (Scheme 3, d.r.…”

“…[2] Among all the possible three-membered ring subunits that have been reported, cyclopropanol derivatives have recently attracted alot of attention as they are found in many natural products and they may undergo,inaddition, alarge variety of synthetic transformations. [3] Va rious strategies can provide cyclopropanols [4] but the most efficient and powerful approach is certainly the Kulinkovich reaction which transforms esters into cyclopropanols by the addition of Grignard reagents to titanium isopropoxide. [5] As the first intermediate of the Kulinkovich transformation is the formation of at itanacyclopropane derivative, [6] thel atter can also be generated in situ by addition of Grignard reagents to an alkene in the presence of Ti(OiPr) 4 (Scheme 1).…”

Cyclopropene Derivatives as Precursors to Enantioenriched Cyclopropanols and n‐Butenals Possessing Quaternary Carbon Stereocenters

“…[21] n-Butenal possessing the allcarbon quaternary stereocenter could therefore be easily prepared in asingle-pot operation and in good yields from the easily accessible cyclopropenyl esters 1e-k as described in Table 2. 93:7) through cyclopropenation of the terminal alkyne with methyl phenyldiazoacetate and [Rh 2 (S-DOSP) 4 ]a st he catalyst (Scheme 3). [22] Having established an easy protocol for the preparation of either 4 or 5 from simple starting materials, the enantioselective synthesis of the cyclopropenylmethyl ether 1d and cyclopropenylmethyl ester 1l were easily achieved in high enantiomeric ratio (e.r.…”

“…[2] Among all the possible three-membered ring subunits that have been reported, cyclopropanol derivatives have recently attracted alot of attention as they are found in many natural products and they may undergo,inaddition, alarge variety of synthetic transformations. [3] Va rious strategies can provide cyclopropanols [4] but the most efficient and powerful approach is certainly the Kulinkovich reaction which transforms esters into cyclopropanols by the addition of Grignard reagents to titanium isopropoxide. [5] As the first intermediate of the Kulinkovich transformation is the formation of at itanacyclopropane derivative, [6] thel atter can also be generated in situ by addition of Grignard reagents to an alkene in the presence of Ti(OiPr) 4 (Scheme 1).…”

Pd‐Catalyzed Selective Remote Ring Opening of Polysubstituted Cyclopropanols

“…Based on the unique reactivity of the cyclopropanol ring, [1] various metal-catalyzed transformations have been reported either for ring-opening reactions [2] or for the preparation of more complex cyclic structures needed for subsequent transformations. [3] These renewed interests have led to the emergence of various stereoselectives ynthesis of stereodefined cyclopropanol derivatives.…”