Jin Kun Cha

C-Acylation of Cyclopropanols: Preparation of Functionalized 1,4-Diketones

A convenient method for preparing attractively functionalized 1,4-diketones has been devised by palladium-catalyzed cross-coupling of cyclopropanols and acyl chlorides. The utility of this method has been demonstrated in an enantioselective synthesis of (+)-myrmicarin 217.

Total Synthesis of Cyathin A3 and Cyathin B2

A stereoselective synthesis of cyathin A(3) and cyathin B(2) has been achieved by a Prins-type reaction of a cycloalkenyl cyclopropanol. Particularly noteworthy is the use of a spirocyclobutanone moiety as a convenient scaffold for an efficient ring-closing metathesis to stereoselectively construct a suitably functionalized seven-membered ring (see scheme).

Low-valent titanium-mediated stereoselective alkylation of allylic alcohols.

We have developed low-valent titanium-mediated 1,3-transpositive cross-coupling reactions of acyclic and cyclic allylic alcohols for the stereoselective introduction of ethyl, 2-silylethyl, 2-phenethyl, and alkenyl groups. Cross-coupling of an allylic alcohol with a vinylsilane or styrene derivative is particularly noteworthy, as an efficient cross-selective coupling of two alkenes has been elusive. The stereochemistry of the cross-coupling alkylation is consistent with syn addition/beta-elimination.

Stereoselective cross-coupling between allylic alcohols and aldimines.

A cross-coupling reaction between an allylic alcohol and an imine is described for stereoselective allylation of aromatic and aliphatic imines. This method provides operationally simple, enantioselective access to functionalized homoallylic amines. Particularly noteworthy is direct use of a functionalized allylic alcohol as an allylating reagent without prederivatization, which obviates the use of preformed organometallic reagents or activated imine derivatives.

C-Alkynylation of Cyclopropanols

Alkynylation of cyclopropanols with 1-bromo-1-alkynes has been devised for easy access to synthetically useful alk-4-yn-1-ones. This method broadens the utility of attractively functionalized cyclopropanols as a new class of homoenolate equivalent in C-C bond formation.

Stereoselective Synthesis of 2,6-trans-Tetrahydropyrans

A stereoselective route to the thermodynamically unfavorable 2,6-trans-tetrahydropyrans has been developed from coupling of hydroxyethyl-tethered cyclopropanols and aliphatic aldehydes. Noteworthy is high convergency from direct coupling of two segments.

Construction of Seven-Membered Carbocycles via Cyclopropanols

A new method for seven-membered ring annulation has been devised by an intramolecular cross-coupling of cyclopropanols and aryl/alkenyl halides. This cyclization reaction is broad in scope and provides easy access to not only fused but also bridged bicyclic compounds.

Stereoselective Alkylation of Allylic Alcohols: Tandem Ethylation and Functionalization†

Transition metal catalyzed allylic substitution is used frequently in organic synthesis. A high level of regioand stereocontrol of asymmetric allylic alkylation is made possible by a judicious choice of substrates, late-transition-metal catalysts, and chiral ligands. Outside the domain of late transition metal catalyzed reactions the use of group IVA metals can also be effective for allylic substitution of readily available allylic alcohols. For example, treatment of acyclic and cyclic allylic alcohols with the ethyl Grignard reagent in the presence of titanium isopropoxide provides stereoselective SN2’-type ethylation products [Eq. (1); El = H]. [4–6] The