Practical Asymmetric Catalytic Synthesis of Spiroketals and Chiral Diphosphine Ligands

Abstract

A practical procedure has been developed for efficient synthesis of chiral aromatic spiroketals and the relevant diphosphine ligands. The procedure includes first asymmetric hydrogenation of readily available α,α′‐bis(2‐benzyloxyarylidene) ketones catalyzed by the Ir(I)/SpinPHOX (S,S)‐1a (0.5–1 mol%) and subsequent hydrogenative deprotection of the resultant benzyl ethers catalyzed by palladium on carbon (Pd/C), as well as simultaneous spiroketalization of the corresponding diphenolic ketones by (S,S)‐1a in one pot. The corresponding chiral aromatic spiroketals (R,R,R)‐4a–j have been obtained in high yields (77–94%) with good diastereoselectivities (trans/cis=81/19 to 96/4), and excellent enantioselectivities for the trans products (97–>99% ee). In addition, the reaction of aromatic spiroketal difluoride (R,R,R)‐4b with potassiodiarylphosphide (KPAr2) in refluxing tertahydrofuran (THF) has also provided an alternative and practical synthesis of chiral spiroketal‐based diphosphine (SKP) ligands in 78–95% yields on multigram scale.magnified image

Synthesis and Reactions of Benzannulated Spiroaminals: Tetrahydrospirobiquinolines

“… 29 , 30 Alternatively, the opposite diastereoisomers do not spirocyclize and exist as amine–imine isomers, which were not isolated chromatographically due to their higher polarities. Attempts were made to isolate these compounds as well as to cyclize them upon treatment with a variety of Lewis and Brønsted acids; 24 however, this was unsuccessful. Further investigations into these systems are ongoing in our laboratory.…”

Making Spiroketal‐based Diphosphine (SKP) Ligands via a Catalytic Asymmetric Approach

“…In order to address these problems, we developed a modi- Wang & Ding fied methodology for chiral spiroketal synthesis in 2013. [14] In this protocol, benzyl group was used to protect the salicylaldehydes, and α,α'-bis(2-benzyloxyarylidene) ketones could be readily obtained in large scale from the direct aldol condensation between the 2-(benzyloxy)benzaldehydes and cyclohexanone. The sequential asymmetric hydrogenation of the C C double bonds using Ir/SpinPhox catalyst and hydrogenolytic debenzylation by Pd/C, followed by the subsequent spiroketalization of the resultant diphenolic ketones, affords the corresponding aromatic spiroketals in high yields with good trans/cis ratios and extremely high ee values in a one-pot approach.…”

Enantioselective construction of C2-symmetric spiro skeleton through intramolecular copper-catalyzed N-arylation

“…Spiroketal has been obtained enantioselectively through Ir-catalyzed asymmetric hydrogenation of α,α'-bis(2-hydroxyarylidene) ketones. 14,15 Very recently, Gong et al have established the use of a chiral iodine reagent as an organocatalyst, where oxidative C-H arylation has furnished enantioenriched spirooxindoles. 16 We have also accomplished an enantioselective synthesis of spirobi(3,4-dihydro-2-quinolone) by using Pd-catalyzed N-arylation referred to as the Buchwald-Hartwig reaction.…”