Facile Synthesis of Versatile Enantioenriched α-Substituted Hydroxy Esters through a Brønsted Acid Catalyzed Kinetic Resolution

Abstract

An efficient synthesis of enantioenriched α-substituted γ-hydroxy esters via a kinetic resolution event is described. Bulky racemic esters in the presence of a chiral Brønsted acid selectively lactonize to yield a recoverable enantioenriched hydroxy ester and lactone. These esters are highly versatile building blocks that can readily be converted to synthetically useful materials.

Use of a Catalytic Chiral Leaving Group for Asymmetric Substitutions at sp3‐Hybridized Carbon Atoms: Kinetic Resolution of β‐Amino Alcohols by p‐Methoxybenzylation

“…In light of the initial results,w ec hose the kinetic resolution of amino alcohols 5 through pmethoxybenzylation (Table 1) as at est reaction. Thek inetic resolution of racemic secondary alcohols through enantioselective protection is an important process,a nd many cata- lytic [10,11] and enzymatic methods [12] have been developed for this purpose.Despite the widespread use of the PMB group in synthetic organic chemistry,t here is no report of enantioselective p-methoxybenzylation of alcohols, [13] in contrast to acylation, [8,14] silylation, [15,16] and acetalization. [17] As olution of Ns amino alcohol 5a,P MB trichloroacetimidate (3; 0.5 equiv), and (R)-binaphthol-derived phosphoric acid 1b [18] (10 mol %) in chloroform was stirred at room temperature in the presence of powdered 4A MS.H owever,t he chiral PMB phosphate derived from 1b and 3 was so unreactive that PMB ether 6a was not produced even after 48 h( Table 1, entry 1).…”

Visible Light and Molecular Iodine‐Mediated Diastereoselective Intermolecular Lactonization of Styrenes with Carbonyls

“…The first method is performed by the intramolecular cyclization reaction of linear starting materials (Scheme a); the methodology is generally used as a first choice for the synthesis of lactones because the methods are generally reliable and robust . The diastereoselective and enantioselective synthesis of lactones was achieved using the abovementioned approach . Although considerable progress has been made in the synthesis of lactones via the cyclization reaction, a multi‐step synthesis to obtain linear starting materials is frequently required.…”

Chiral Brønsted Acid Catalyzed Kinetic Resolutions

“…We recently reported an asymmetric synthesis of a-substituted g-hydroxy esters (AE)-39 through aB r ønsted acid catalyzed kinetic resolution with TRIP (23) (Scheme13). [15] This intramolecular transesterification was effectivef or substrates with small substituentsa tt he a position (such as R 1 = CH 3 and R 2 = H, s = 20) andw hen forming an allcarbon quaternary stereocenter (R 1 = CH 3 and R 2 = Ph, s = 16.7).…”