A Mechanistic Investigation of the Kinetic Resolution of Secondary Aromatic Alcohols Using a Ferrocene‐Based Planar Chiral 4‐(Dimethylamino)pyridine Catalyst

Abstract

A detailed computational and kinetic analysis of the acetylation of 1-phenylethanol with acetic anhydride catalyzed by planar chiral 4-(dimethylamino)pyridine (DMAP) catalyst (-)-1 is presented. The study includes a computational investigation of the potential-energy surface including the acylation and stereoselective transition states at the DFT level of theory. Experimentally, the kinetic study shows that the reaction proceeds in a first-order manner in catalyst, whereas both substrates, acetic anhydride and 1-phenylethanol, show fractional order, which is in accordance with steady-state conditions. The fractional order depends on an equilibrium between the free catalyst and the acetylated catalyst.

Visual kinetic analysis

“…RPKA has been applied by academic and industrial research groups for a diverse range of reactions including precious metal-catalysed reactions, [8][9][10][11][12] rst row metal catalysis [13][14][15] and organocatalysis. [16][17][18][19][20] Plots using concentration profiles…”

Cation−π Interactions in Organic Synthesis

“…Desymmetrization of meso-diol 228 provided monoester 229 in 91% yield with 99.7% ee (Scheme 61b). 181 The extended π system on the propargylic alcohols 183 and aryl alkyl carbinols 184 185 Spivey developed an atropisomeric biaryl catalyst 231 for asymmetric acylation. Among various sec-alcohols employed, the s value of cis-cyclohexane-1,2-diol monobenzoate 232 was higher than those of the other substrates without an aryl moiety, indicating the contribution of an interaction between the pyridinium and the aromatic ring of the substrates in the transition state TS-233 (Scheme 62).…”

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.…”

“…The biological relevance of chiral alcohols has driven the development of many methods for their kinetic resolution (KR), which have been subjected to numerous experimental and theoretical studies . Among available strategies for the KR of alcohols, chiral 4‐dimethylaminopyridine (DMAP) catalyzed KRs are particularly appealing due to their operational simplicity, high turnover, and environmental friendliness .…”