Resolution of Diols via Catalytic Asymmetric Acetalization

Abstract

A highly enantioselective kinetic resolution of diols via asymmetric acetalization has been achieved using a chiral confined imidodiphosphoric acid catalyst. The reaction is highly efficient for the resolution of tertiary alcohols, giving selectivity factors of up to >300. Remarkably, even in cases where the selectivity factors are only moderate, highly enantioenriched diols are obtained via a stereodivergent resolution to diastereomeric acetals.

Understanding the Reactivity and Selectivity of Fluxional Chiral DMAP‐Catalyzed Kinetic Resolutions of Axially Chiral Biaryls

“…The biological relevance of chiralalcohols hasdriven the development of many methods for their kinetic resolution (KR), which have been subjected to numerous experimental and theoretical studies. [1][2][3][4][5][6][7][8][9][10][11][12][13] Amonga vailables trategies for the KR of alcohols, chiral 4-dimethylaminopyridine (DMAP) catalyzed KRs are particularly appealingd ue to their operational simplicity,h igh turnover,a nd environmental friendliness. [14][15][16][17][18][19] Studying such reactions computationally not only enriches our understanding of thesep rocesses but also creates opportunities to improvetheir efficiency.…”

Kinetic Resolution of Tertiary 2‐Alkoxycarboxamido‐Substituted Allylic Alcohols by Chiral Phosphoric Acid Catalyzed Intramolecular Transesterification

“…However, because of the relatively challenging demand for spatial differentiation between three R groups and the intrinsic reaction requirements, highly efficient kinetic resolution processes of tertiary alcohols that provide both the unreacted starting material and the product with high enantioselectivity are still quite limited. For example, List and co‐workers reported an excellent chiral Brønsted acid catalyzed kinetic resolution of homoaldol compounds and diols with tertiary hydroxy groups that is based on intra‐ and intermolecular acetalizations and generated the both tertiary alcohol starting materials and acetal products with high enantioselectivities . The groups of Zhao and Smith reported highly efficient kinetic resolutions of tertiary heterocyclic alcohols based on asymmetric acylation reactions enabled by NHC and isothiourea catalysis, respectively.…”

Chiral Brønsted Acid Catalyzed Kinetic Resolutions

“…Recently,L ist and co-workers reported another kinetic resolution utilizing chiral imidophosphoric acids 17 b and 17 c (Scheme 6). [9] Here, diols (AE)-18 with at ertiary stereocenter underwenta na symmetric acetalization with aldehyde 19 to yield enantioenriched acetals 20 with good diastereoselectivity and recovered enantioenriched alcohols 18.S electivity factors were best (up to 389) when R 1 = aryl and n = 1, and aldehydesw ith steric bulk at the b-carbon were used. An oxocarbenium intermediate where the tertiarya lcohola nd the aldehyde form hydrogen bonds to the chiral imidodiphosphate anion and the aldehyde alkyl chain and largera lcohol substituent takep seu- An ovel kineticr esolution of alcohols via an S N 2-type alkylation mechanism was recently reported (Scheme 7).…”