Access to Optically Pure β-Hydroxy Esters via Non-Enzymatic Kinetic Resolution by a Planar-Chiral DMAP Catalyst

Abstract

Abstract:The development of new approaches to obtain optically pure β-hydroxy esters is an important area in synthetic organic chemistry since they are precursors of other high value compounds. Herein, the kinetic resolution of racemic β-hydroxy esters using a planar-chiral DMAP derivative catalyst is presented. Following this procedure, a range of aromatic β-hydroxy esters was obtained in excellent selectivities (up to s = 107) and high enantiomeric excess (up to 99% ee). Furthermore, the utility of the present method was demonstrated in the synthesis of (S)-3-hydroxy-N-methyl-3-phenylpropanamide, a key intermediate for bioactive molecules such as fluoxetine, tomoxetine or nisoxetine, in its enantiomerically pure form.

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).…”

“…Desymmetrization of meso -diol 228 provided monoester 229 in 91% yield with 99.7% ee (Scheme b) . The extended π system on the propargylic alcohols and aryl alkyl carbinols led to higher selectivity, suggesting the contribution of a cation−π interaction in the transition state of the acylation.…”

Well‐Defined Chiral Copper NHC Complex in the Asymmetric Conjugated β‐Borylation and One‐Pot Metathesis‐Asymmetric β‐Borylation Reactions

“…However, synthetic routest oe nantiomerically pure b-hydroxyl esters are still limitedi nn umber. [17] Therefore, developing practical and generalm ethods for the preparation of libraries of such compounds from simple substrates is of importance.S ince the discovery of stable molybdenuma nd ruthenium alkylidene catalysts, olefin metathesis has becomeaversatile and powerful tool for target-oriented organic synthesis, as well as in biological and material science. [18,19] One-pot cross metathesis is of high value in modern organic chemistry,s ince it not only results the synthesis of numerousp roducts easier and in a cheaper way,b ut can also induce new conceptsi ns ynthetic planning.…”

Dynamic kinetic resolution of α-F-β-ketone amides (esters) via Ir/f-diaphos-catalyzed asymmetric hydrogenation

“…1 e Additionally, HCV RNA replication inhibitors like sofosbuvir, used in treating chronic hepatitis C, demonstrate excellent pharmaceutical activity. 2 Compound A , an analog of a vermin-killing herbicide, 3 and compound B , an analog of nisoxetine, hold potential significance, 4 but the preparation of these substances has been seldom reported. In 1991, Yoneda and colleagues presented a synthetic method for chiral β-fluoro alcohols through ring-opening of epoxides, albeit with the drawback of the hazardous reagent HF (Scheme 1A).…”