Perkin communications. Biocatalytic asymmetric cycloaddition of benzonitrileN-oxides toN-vinylcarbazole

摘要

J. CHEM. SOC. PERKIN TRANS. 1 1990 Perkin Communications BiocataIytic Asymmetric Cycloaddition of Benzonitrile N-Oxides to N-Vinylcarbazolet K. Rama Rao," Y. V. D. Nageswar and H. M.Sampathkumar Organic Chemistry- I, Indian Institute of Chemical Technology, Hyderabad-500 007, India Baker's yeast catalyses asymmetric cycloaddition of the benzonitrile N-oxides 2-4 to N-vinylcarbazole 1 to yield optically active 4,5-dihydroisoxazoles 5-7 in good yields with an enantiomeric excess (ee) of up to 51. Table 1. 3-Aryi substituted 5-carbazol-9-yl-4,5-dihydroisoxazoles. Products Compd. Yield Molecular no. R' R2 () M.p. ("C) formula (")" Ee Xb 5 Me Me 78 132-133 C2,H2,N20 + 127.9 50.7 6 OMe OMe 80 236 C24H22N2O4 +21.3 25.4 7 CI H 75 229-230 C21Hl,N20C12 + 11.4 17.6 a c 1.0 in CHCI,.Determined by 'HNMR (200 MHz) spectroscopy with Eu(hfc), as chiral shift reagent. In continuation of our work on the utility of enzymes as All the compounds were characterised on the basis of elemental catalysts in organic synthesis,'.' we report herein, the asym- analysis and 'H NMR and mass spectral data. The structural metric 1,3-dipolar cycloaddition of the benzonitrile N-oxides assignments are in conformity with our earlier observation^.^ 2-4 to N-bhylcarbazole 1 in the presence of Baker's yeast The results for the optically active 4,5-dihydroisoxazoles 5-(Saccharomyces cereuisiae). This biocatalytic asymmetric cyclo- 7 obtained are shown in Table 1. Among the compounds addition proceeds without a chiral auxiliary in either dipole or studied, the 4,5-dihydroisoxazole 5 formed from 2,4,6-tri-dipolarophile and yields, for the first time, optically active methylbenzonitrile N-oxide 2 has shown enhanced en-dihydroisoxazoles attached to a heterocyclic nitrogen 5-7 antioselectivity with an ee up to 51.The higher symmetric (Scheme 1). These compounds have potential in various bias observed for the cycloaddition with 2 may be due to stereocontrolled syntheses since 4,5-dihydroisoxazoles repre- favourable control of geometry in the approach of the dipole sent the masked form of an array of different f~nctionalities.~.~ and dipolarophile at the 'active site'. Thus, biocatalytic This cycloaddition proceeds to yield only one regioisomer, i.e. cycloaddition of the N-oxides 2-4 to N-vinylcarbazole 1 3-aryl-substituted 5-carbazol-9-yl-4,5-dihydroisoxazoles5-7 proceeds with appreciable enantioselectivity and further HOMO(dipolarophile)and is a LUMO(dipol,)-controlled reaction. application of this reaction is currently under study. HC+ R' 7.2 buffer (8.5 ml) was added N-vinylcarbazole 1(1 mmol) in 30CH2 ethanol (10 ml) followed by the benzonitrile N-oxide 2-4 (1 (11 (2) R1= R2= Me mmol) in 30yi ethanol (10 ml). The mixture was incubated at (3) R' = R2= OMe 37 "C for 24 h. It was then extracted with chloroform (2 x 20 (4) R' = CI, R2= H ml) and the extract dried and evaporated and the residue purified by recrystallisation from chloroform-hexane (1 :1).