No abstract

[Chemical reaction: See text] Lewis acid promoted radical conjugate additions to beta-substituted alpha,beta-unsaturated alpha-nitro esters and amides were investigated. With achiral Lewis acids, there was competition between the desired radical conjugate addition and undesired alkene reduction mediated by Bu3nH. Zinc Lewis acids provided the greatest amounts of addition products with both substrate classes. Studies with Bu3nD indicated that the acidic alpha-stereocenter of the alpha-nitro ester products does not racemize under controlled workup conditions. The corresponding alpha-nitro amides racemized significantly during chromatography, but this problem could be greatly minimized by subjecting the crude adducts to subsequent transformations. Indium-mediated reduction of the nitro group followed by acylation of the resulting amine provided good yields of beta-substituted alpha-amino acid derivatives with mimimal levels of racemization. Attempts to use chiral Lewis acids in a stereoselective variant of this process revealed that Kanemasa's DBFOX/Ph ligand (14a) was uniquely effective. Moderate to good ee's and low dr's were obtained with amide substrates. Determination of the absolute configurations of the syn and anti isomers of adduct 7b showed that the hydrogen atom abstraction step was significantly more stereoselective than the radical conjugate addition step. A model for substrate binding to the chiral Lewis acid is presented.

[reaction: see text] Chiral phase-transfer catalyst 5 containing an electron-deficient trifluorobenzyl moiety promoted the alkylation of glycine derivative 6 with propargyl bromide 7a in good yield and excellent ee. The resulting propargyl glycine 8 was converted to 14, the central tryptophan residue of Celogentin C, in two steps, with the Pd-catalyzed heteroannulation as the key transformation. This method promises to be an efficient route for the preparation of tryptophan derivatives possessing substitution on the indole ring.

[reaction: see text] The tricyclic core of the bioactive natural product acutumine has been synthesized. Key steps include an oxidative phenolic coupling to form a masked o-benzoquinone, an anionic oxy-Cope rearrangement to construct an all-carbon quaternary center, and a Michael-type cyclization to form an amine-bearing quaternary carbon. The target compound exists in solution as an enol, in contrast to related compounds that are ketones. A model explaining these observations is presented.

The Cinchona alkaloid derived chiral ammonium salt developed by Park and Jew functions as an effective catalyst for the synthesis of beta-hydroxy alpha-amino acids via asymmetric aldol reactions under homogeneous conditions. The syn diastereomers are obtained in good ee, and aryl-substituted aliphatic aldehydes are the best substrates for the reaction. These results represent the highest ee's obtained to date in direct aldol reactions of glycine equivalents catalyzed by inexpensive, readily prepared chiral ammonium salts.