The Mo-catalyzed asymmetric allylic alkylation using azlactones provides extraordinary levels of selectivity. Thus, a wide range of cinnamyl-type substrates react with 2-methyl and 2-benzyl azlactones to give only the product resulting from attack at the more substituted carbon. Using other alkyl substituents such as 2-methylthioethyl, isobutyl, allyl, and isopropyl provides products that still retain excellent regioselectivity but small quantities of the linear product are also observed. In all cases, excellent diastereo- and enantioselectivity of the branched alkylated product are observed. This new asymmetric reaction provides ready access to unusual quarternary amino acids, important building blocks for biological applications. The reactions complements the Pd AAA wherein the cinnamyl substrate leads to only the product of attack at the primary terminus of the allyl moiety.

AbstractΔ 9 -THC is synthesized in enantiomericaly pure form, where all of the stereochemistry is derived from the molybdenum catalyzed asymmetric alkylation reaction of the extremely sterically congested bis-ortho substituted cinnamyl carbonate in high regio-and enantioselectivity.(-)-Δ 9 -trans-Tetrahydrocannabinol (Δ 9 -THC) 1, isolated 1 from female Cannabis sativa L. in 1964 has been identified as the primary psychomimetic component of marijuana. It is also known to show antiemetic, antiglaucoma, and analgesic properties. Currently it is administered as an antinauseant to patients undergoing chemotherapy. Discovery of the cannabinoid receptors CB1 and CB2 and Δ 9 -THC analogues 2 that bind selectively to them has led to a need for the development of a flexible synthetic route which would yield target compounds easily in high yields and in sterochemically pure form.THC itself has been prepared numerous times, though most routes are either racemic or derive their chirality from chiral building blocks. 3 Only Evan's 4 route targets the natural product enantioselectively from achiral starting materials. The problems associated with the synthesis of THC involve the control of cis-trans stereochemistry at the cyclohexene ring and the position of the double bond i.e. Δ 9 vs. Δ 8 , the latter being thermodynamically more stable.Our reterosynthetic analysis of the molecule envisioned all of the stereochemistry resulting from a single Mo-catalyzed asymmetric allylic alkylation (AAA) reaction (See abstract). Alkylation of malonate adduct 4 with 3 should furnish the substrate for ring-closing metathesis (RCM). The RCM in itself results in a fixed geometry of double bond thus solving the problem of co-formation of Δ 8 -THC seen in many syntheses. Decarboxlylation of the malonate after RCM was planned to result in the required trans stereochemistry of 2. Grignard addition to ester 2 followed by demethylation to the free phenol and cyclization yields 1. aromatic group in 5, the alkylating partner 3, or the Grignard reagents one can potentially prepare different analogues of THC without fundamentally changing the chemistry involved.Allyl alcohol 9 was easily prepared in high yield from commercially available olivetol, 6 in 4 steps (Scheme 1). Lithiated dimethyl olvitol was quenched with dry DMF to yield the aldehyde 8 in 83% yield. Wadsworth-Horner-Emmons reaction of 8 with sodium triethylphosphonoacetate resulted in the corresponding α,β-unsaturated ethyl ester, which was subjected without further purification to DIBAL-H reduction to yield 97% of 9. Preparation of carbonate 5 proved to be a little tricky because the compound is sensitive to both acid and base, including silica chromatography conditions. A preparation of 5 clean enough to take into the Mo-alkylation reaction, was achieved by titrating alcohol 9 with BuLi at -78 °C in ether and quenching the resulting alkoxide with methyl chloroformate also at -78 °C. Washing the organic layer with ice-cold water followed by solvent removal gave carbonate 5 as a waxy solid,...

5H-Alkyl-2-phenyl-oxazol-4-ones, a little-known heterocyclic ring system, are readily available via a microwave-assisted, sodium fluoride catalyst cyclization of mono-alpha-haloimides, which in turn are accessed by N-acylation of benzamides with alpha-bromo acid halides. Terminally substituted allyl systems serve as excellent substrates for Mo-catalyzed asymmetric allylic alkylation. The resultant products are formed with excellent ees involving a catalyst derived from N,N'-bis-picolinamide of trans-1,2-diaminocyclohexane and cycloheptatriene molybdenum tris(carbonyl). In addition to benzenoid, nonbenzenoid aromatic and vinyl substituents on the allyl carbonate moiety provide good to excellent regio- and diastereoselectivity as well as excellent enantioselectivity. Substituents on the heterocycle include methyl, n-butyl, allyl, isobutyl, isopropyl, and cyclohexyl. The presence of a double bond in the product allows them to be further modified via the chemistry of the double-bond, including metathesis. The products are hydrolyzed under basic conditions to provide alpha-hydroxyamides.

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diastereoselective syntheses, enantioselective syntheses diastereoselective syntheses, enantioselective syntheses (incl. cis/trans-isomerism) O 0031 -033Designed Ligands as Probes for the Catalytic Binding Mode in Mo-Catalyzed Asymmetric Allylic Alkylation.-In order to understand the extraordinary levels of regio-and enantioselectivity obtained with the catalytic system based on both enantiomeric ligands [(Ia) or (VIIa)] and molybdenum in the title reaction, the reaction of carbonates (II), (VI), and (VIII) with malonate (III) is studied by use of ligands with modified substituents. The results are compared with those obtained with the original ligands (Ia) and (VIIa). Possible binding modes of these ligands to molybdenum during the catalytic cycle are discussed. -(TROST, BARRY M.; DOGRA,