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

Abstract

The diastereoselective carbocupration reaction of cyclopropenylmethyl ethers followed by addition of oxenoid leads to the formation of diastereo-and enantiomerically enriched 2,2,3,3-tetrasubstituted cyclopropanol derivatives. Ring fragmentation of the copper cyclopropanolate leads to acyclic butenal derivatives possessing enantiomerically enriched a-quaternary carbon stereocenters in as ingle-pot operation.

Directed Cu(I)-Catalyzed Carbomagnesiation of 1-Arylcycloprop-2-ene-1-carboxamides En Route to Densely Substituted Functionalized Cyclopropanes

“…6 Mode II includes the processes in which the facial selectivity of carbometalation is governed by a directing group at C-3. Suitable directing functionalities successfully employed in these transformations include alcohol, 7 ester, 8 ether, 9 and Evans' chiral oxazolidinone auxiliaries. 10 Recently, Marek reported the application of 2-alkyl-N,N-dimethylcycloprop-2ene-1-carboxamides (1) easily available via the well-established asymmetric cyclopropanation methodology, 11 in the copper-catalyzed, directed addition of Grignard reagents (Scheme 2).…”

Asymmetric Catalytic Preparation of Polysubstituted Cyclopropanol and Cyclopropylamine Derivatives

“…As reported, [14] the catalytic diastereo-and enantioselective carbometalation of cyclopropenes 1 was easily achieved by addition of 1.5 equiv of Grignard reagent R 1 MgBr in the presence of acatalytic amount of copper salt Cu(CH 3 CN) 4 PF 6 (2 mol %) and chiral catalyst (R,S)-Josiphos (2.2 mol %) in Et 2 OatÀ5 8 8Cin30min (Scheme 2). [16] Similarly,t he carbometalationoxidation process proceeds syn to the adjacent methyl group on C3 even when secondary alkyl Grignard species are involved (Scheme 2; formation of 3e, 3f). [15] By employing these experimental conditions,alarge variety of cyclopropanol derivatives were obtained in excellent diastereo-and enantioselectivity (Scheme 2).…”

“…[15] By employing these experimental conditions,alarge variety of cyclopropanol derivatives were obtained in excellent diastereo-and enantioselectivity (Scheme 2). [16] For 3o,t he enantiomeric ratio was determined for the benzyl ester (see the Supporting Information). 98:2, er up to 99:1).…”

“…In all cases,t he R 1 group of the Grignard species at C1 and the hydroxy group at C2 are in a syn relationship,supporting the hypothesis that the carbometalation reaction occurs in a syn fashion and that the resulting magnesium-to-copper transmetalation as well as the electrophilic oxidation reaction proceed with pure retention of configuration as determined by NOE experiments (see the Supporting Information). [16] Similarly,t he carbometalationoxidation process proceeds syn to the adjacent methyl group on C3 even when secondary alkyl Grignard species are involved (Scheme 2; formation of 3e, 3f). [14] It should be noted that for only two cyclopropanols (3k and 3q), the enantiomeric ratios could not be directly determined by HPLC analysis of 3;instead, the hydrolyzed cyclopropanes 2 were analyzed (knowing that the oxidation proceeds with pure retention of configuration).…”

“…[14] It should be noted that for only two cyclopropanols (3k and 3q), the enantiomeric ratios could not be directly determined by HPLC analysis of 3;instead, the hydrolyzed cyclopropanes 2 were analyzed (knowing that the oxidation proceeds with pure retention of configuration). [16] For 3o,t he enantiomeric ratio was determined for the benzyl ester (see the Supporting Information). Cyclopropene derivatives with different substituents on the aromatic ring also provided the expected cyclopropanols with high diastereo-and enantioselectivity (3k-3m).…”