Abstract

Diels-Alder reactions of benzylidenecyanomethyl-1,3-benzothiazoles 17 and -1,3-benzoxazoles 18 as 1-aza-1,3-butadienes are described. The dienes 17 and 18 featuring stabilized imine moieties in the form of heteroaromatic rings react with both electron-deficient and electron-rich dienophiles to give corresponding cycloadducts regioselectively. The cycloadditions of the intramolecular systems 34c,d and 35c,d proceeded smoothly via the exo-transition state, stereoselectively affording polycyclic compounds 36c,d and 37c,d in good to excellent yields. The diene systems of 17 and 18 were extended to dienes 19a-c with ester groups at diene-4-positions. Dienes 19a-c exhibited high Diels-Alder reactivities with electron-rich alkenes. Dienes 19a-c also reacted with allyl alcohols 55-58 in the presence of stanoxane catalyst 53 to give cycloadducts 59-62 via transesterification and intramolecular cycloaddition. Although alpha-alkoxycarbonylnitrones 64 have been very attractive nitrones for the syntheses of amino acids, the nitrones 64 exist as equilibrating mixtures of (E)-64 and (Z)-64. To solve this problem, three methods were explored: 1) sequential transesterification and intermolecular cycloaddition of nitrones 64 with allyl alcohols; 2) use of chiral and geometry-fixed nitrone 84; and 3) selective activation of (Z)-64 by Eu(fod)3. These methods were applied to syntheses of nikkomycins, clavalanine, and beta-substituted alpha-amino acids. The reactions of photoinduced carbonyl ylides from alpha,beta-unsaturated gamma,delta-epoxy nitriles were studied. Direct irradiation (lambda = 254 nm) of (E)-129 led selectively to products arising from the carbonyl ylide XXV or the carbene intermediate XXVI. The carbonyl ylides generated from (E)-129, (E)-139, and (Z)-143 were trapped with MeOH in the presence of amine, affording the corresponding acetals in moderate yields (Schemes 42 and 43). Photocyclization reactions of delta-hydroxyalkyl epoxy nitriles 148a-e led to spiro acetals arising from the carbonyl ylides (Scheme 45). The photoinduced carbonyl ylides from the epoxy dinitriles 158 and 160-163 underwent 1,3-dipolar cycloaddition with enol ethers, leading to a tetrahydrofuran system (Schemes 49 and 50, Table 14). Electrocyclization of 3-butadienylindoles 184 to intermediary dihydrocarbazoles XXXII followed by elimination of MeOH gave 3-oxyganated carbazoles 185, which were transformed to carbazole alkaloids hyellazole 168, 4-demethoxycarbazomycin B 170 and carazostatin 171, respectively. Claisen rearrangement of 3-(1-amino-1-vinyloxy) indolines derived from 3-hydroxyindolines 192 and amide acetal 193 gave indol-4-ylacetamides 194, which was reduced to afford 4-(2-aminoethyl) indoles 198, which has a framework of biologically active 4-substituted indole compounds. Claisen rearrangement of 3-allyloxyindoles produced in situ by condensation of indolin-3-ones 202 with allyl alcohols 203 and 206-211 gave 2-allylindolin-3-ones 204, 205 and 212-220. The domino reactions, Horner-Wadsworth-Emmons olefination of 2-allyloxyindole 233, isomerization, and Claisen rearrangement produced 3-allylindolin-2-one 234, which was derivatized to 3a-allylpyrrolo [2,3-b] indole alkaloid, flustramine C 221. Reverse aromatic Cope rearrangement of 2-allyl-3-indolidene acetonitriles 241-243, formed by Horner-Wadsworth-Emmons reaction of 2-allylindolin-3-ones 238-240, afforded indoles 244-246.