Three-component condensation of o- and p-methoxytoluenes with isobutyraldehyde and α-substituted benzyl cyanides. Synthetic approach to analogs of natural alkaloids

Abstract

Three-component condensation of o(p)-methoxytoluene with isobutyraldehyde and α-substiituted benzyl cyanides gave 8-acetyl-3,6,6-trimethyl-5,6,7,12b-tetrahydrodibenzo[d,f]indol-2(1H)-one or 8-acetyl-1,6,6-trimethyl-3,4,5,6,7,12b-hexahydrodibenzo[d,f]indol-3-one. Analogous reaction of p-methoxytoluene with isobutyraldehyde and 1-phenylcyclopentane-1-carbonitrile afforded 1′,6′,6′-trimethyl-3′,4′,5′,6′,7′,12b′-hexahy-We reported previously that three-component condensation of anisole with isobutyraldehyde and phenylacetoacetonitrile yields 3,3-dimethyl-1-(2-oxo-1-phenylpropylidene)-2-azaspiro[4.5]deca-6,9-dien-8-one [1]. Analogous spiro heterocycle A was obtained by reaction of o-methoxytoluene with isobutyraldehyde and methyl thiocyanate [2]. addition, we isolated minor compound II with the same molecular weight but different 1 H NMR spectrum (Scheme 1). The 1 H NMR spectrum of I contained a singlet at δ 1.41 ppm from protons in the methyl group on C 7 , a singlet at δ 6.64 ppm from 6-H, and a doublet at δ 5.58 ppm (J = 9.9 Hz) from 10-H. The 9-H signal was overlapped by aromatic multiplet at δ 6.91-7.03 ppm. In the 1 H NMR spectrum of II we observed only one singlet at δ 6.43 ppm from the 4-H proton, and three protons gave rise to an ABM pattern in the aliphatic region. Signals from two carbon atoms in the dienone fragment were displaced to aliphatic region of the 13 C NMR spectrum. Methylene protons on C 5 resonated as an AB spin system at δ 1.90 ppm (J = 12.8 Hz), and those on C 1 also appeared as an AB pattern centered at δ 2.74 ppm (J = 16.5 Hz). These findings, in combination with the data of elemental analysis, allowed us to assign the structures of 3,3,7-trimethyl-1-(2-oxo-1-phenylpropyl)-2-azaspiro[4.5]-