Exploiting sequential lipase-catalyzed reactions to achieve enantiomerically pure chiral primary alcohols

Abstract

The lipase-catalyzed enantioselective acetylation of benzofused cycloalkanescontaining primary alcohols with vinyl acetate was performed and allowed the isolation of enantiopure alcohols. Lipases from P. cepacea, C. rugosa, C. antarctica, P. fluorescens, C. cylindracea and M. meihei exhibited remarkable activity towards acetylation of these alcohols, affording the corresponding acetates with high conversion. Due to the high lipase activity toward primary alcohols, the enantioselectivity was low. To circumvent this problem, sequential kinetic resolution was employed with enantiocomplementary lipases leading to enantiomerically pure primary alcohols. This method represents a new approach to obtain chiral building blocks bearing ring systems, such as indanes, chromanes and tetralins. (6), 79 (6), 77 (11). 1 H NMR (300 MHz, CDCl 3 ) δ 7.25 -7.08 (m, 2H), 7.01 -6.74 (m, 2H), 6.85 (dd, J = 8.0 and 1.5 Hz, 1H), 4.39 (dd, J = 11.2 and 5.1 Hz, 1H), 4.32 -4.10 (m, 3H), 3.18 (hex, J = 3.2 Hz, 1H), 2.11 (s, 3H), 2.04 -1.86 (m, 1H), 0.99 -0.77 (m, 1H).

Rh-Catalyzed Asymmetric Hydrogenation of β-Branched Enol Esters for the Synthesis of β-Chiral Primary Alcohols

“…However, most of these reports concern the construction of chiral secondary and tertiary alcohols, while the preparation of chiral primary alcohols has been less studied. Enzyme-catalyzed (dynamic) acylative kinetic resolution of racemic β-branched primary alcohols and dynamic reductive kinetic resolution of racemic α-branched aldehydes are the most attractive methodologies for the synthesis of such compounds with satisfactory enantioselectivities. Two indirect methods, asymmetric hydroboration/oxidation of 1,1-disubstituted alkenes and asymmetric carboalumination/or carboboration/oxidation of 1-substituted alkenes, have also been developed.…”

1‐Hydroxymethyl‐7‐oxabicyclo[2.2.1]hept‐2‐ene skeleton in enantiopure form through enzymatic kinetic resolution

“…32,33 While secondary alcohols undergo acylation with better selectivity, [37][38][39][40][41][42][43][44][45][46][47] primary -OHs are generally less discriminated by lipases unless in the vicinity of sterically demanding groups. [48][49][50][51][52][53][54][55][56][57][58][59] Several strategies have been attempted to overcome this, such as the use of chiral or sterically demanding acyl donors, 56,60 optimization of solvation conditions, 61 or through sequential resolutions. 54,55 As mentioned earlier, such skeletons are valuable intermediates in the synthesis of various natural product analogues for diverse applications.…”

Exploring the iodine(III)-mediated ring contraction: new substrates, novel conditions and asymmetric reactions

“…The protocol uses inexpensive, readily accessible, and stable chemicals (PhI, mCPBA, TsOH) giving rearrangement products in yields comparable to those obtained using the more expensive commercially available HTIB.Additionally, a new route for the one step transformation of 4-methyl-1,2-dihydronaphthalene into 1-methyl-2-tetralone using mCPBA and TsOH was developed. The prepared primary alcohols were subjected to lipase-catalyzed enantioselective acetylation to get chiral nonracemic indanes, chromanes and tetralins (Leandro H. Andrade* and Rodrigo S. Martins) 152. Finally, we have studied the reactivity of various chiral iodine(III) compounds with 1,2dihydronaphthalenes.…”