Stereospecific Cross-Coupling Reactions of Aryl-Substituted Tetrahydrofurans, Tetrahydropyrans, and Lactones

Abstract

The stereospecific ring-opening of O-heterocycles to provide acyclic alcohols and carboxylic acids with controlled formation of a new C–C bond is reported. These reactions provide new methods for synthesis of acyclic polyketide analogs with complex stereochemical arrays. Stereoselective synthesis of the cyclic template is utilized to control relative configuration; subsequent stereospecific nickel-catalyzed ring-opening affords the acyclic product. Aryl-substituted tetrahydrofurans and tetrahydropyrans undergo nickel-catalyzed Kumada-type coupling with a range of Grignard reagents to furnish acyclic alcohols with high diastereoselectivity. Enantioenriched lactones undergo Negishi-type cross-coupling with dimethylzinc to afford enantioenriched carboxylic acids. Application in a two-step enantioselective synthesis of an anti-dyslipidemia agent is demonstrated.

Well-defined nickel and palladium precatalysts for cross-coupling

“…The [(dppe)NiCl 2 ] precatalyst has also been extensively used in Kumada couplings. Jarvo and co-workers reported the alkylation of secondary ethers 127 and the ring opening of oxygen-containing heterocycles with alkyl Grignard reagents 128 . The alkylation of allylic alcohols and ethers has also been reported with methylmagnesium iodide and [(dppe)NiCl 2 ] as a precatalyst 129,130 .…”

Recent Advances in Methylation: A Guide for Selecting Methylation Reagents

“…Similarly, as discussed in Section 2.21.1, in which MeLi is used in metal‐catalyzed cross‐couplings, Grignard reagents have been used in the presence of different metal catalysts for functional group transformation, stereospecific ring‐opening of aryl‐substituted tetrahydrofurans, and C−H activation (Scheme ).…”

“…Compared with Grignard reagents, alkyl zinc reagents usually provide better functional group tolerance . In 2012, Jarvo et al.…”

“…In the presence of the Ni II catalyst, the ring‐opening product 292 was obtained in 93 % yield when MeMgI was used (Scheme ). In the same paper, the cross‐coupling reaction of chiral lactones ( 300 ) with Me 2 Zn affords highly stereoselective ring‐opening products ( 301 ) in high yields (Table ) . Recently, Me 2 Zn has been used to transform aryl sulfonyl chlorides into aryl methyl thioethers ( 302 ; Table ) …”

Nickel‐Catalyzed Enantioselective CC Bond Formation through CO Cleavage in Aryl Esters

“…[2,3] Despite the advances realized, [1] the development of asymmetric CÀO bond cleavage reactions using ester derivatives remains largely undeveloped. In recent years, elegant stereoselective transformations have recently been reported by the groups of Jarvo [4] and Watson [5] (Scheme 1, path a) using ester counterparts; unfortunately, these methods are restricted to the formation of tertiary stereocenters, requiring the installation of a preexisting stereogenic center. In sharp contrast, an enantioselective C À C bond formation through C sp 2 À O bond cleavage with prochiral nucleophilic entities that obviates the need for organometallic reagents and results in the rather elusive quaternary stereogenic centers has not yet been described in the literature.…”