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This paper describes an efficient tandem sequence for the synthesis of 1,2,3,4-tetrahydro-β-carbolines (THBCs) relying on a ruthenium hydride/Bronsted acid-catalyzed isomerization of allylic amides to N-acyliminium ion intermediates which are trapped by a tethered indole nucleophile. The methodology provides not only a convenient "aldehyde-free" alternative to the classical Pictet-Spengler reaction but also attractive possibilities for total synthesis, including rapid generation of molecular complexity and formation of quaternary stereogenic centers. TBHCs can also be accessed by harnessing the Suzuki cross-coupling reaction to the isomerization/N-acyliminium cyclization sequence. Finally, diastereo- and enantioselective versions of the title reaction have been examined using substrate control (with dr >15: 1) and asymmetric catalysis (ee up to 57%), respectively.

A mild, racemization-free, palladium-catalyzed alpha-arylation of tetramic acids (2,4-pyrrolidinediones) has been developed. Various amino acid-derived tetramic acids were cleanly arylated by treatment with 2 mol % of Pd(OAc)(2), 4 mol % of a sterically demanding biaryl phosphine, 2.3 equiv of K(2)CO(3) or K(3)PO(4), and aryl chlorides, bromides, or triflates in THF. With conventional heating, conversions95% could be attained after 1 h at 80 degrees C, whereas microwave-induced heating led to much shorter reaction times (5 min at 110 degrees C). The electron density of the aryl electrophile had no effect on their reactivity: both electron-rich and electron-poor aryl chlorides and bromides or triflates led to good yields. Ortho-substituted aryl halides and heteroaryl halides, however, did not undergo the title reaction.

The reaction of stabilized Peterson reagents (alpha-silyl ester enolates) with ketones has been studied theoretically and experimentally. Enolate geometry was studied by trapping experiments and NMR spectroscopy and was found to differ markedly with the nature of the base (LiHMDS vs LDA vs KHMDS). The chelating effect of the lithium counterion was found to be critical for the reaction. For the two ketones studied, the combined weight of experimental and computational data assigns geometrical selectivity to the initial addition transition state, though in general there appears to be a fine balance between three possible choices for the rate-determining step.

[reaction: see text] This paper describes the total synthesis of the naturally occurring alkaloids pinnamine (1) and anatoxin-a (2) from a common enantiomerically pure intermediate (7) easily available from pyroglutamic acid. The synthesis of enantiopure pinnamine proceeded in 10 steps and 4.8% overall yield, and the route was flexible enough to allow stereocontrolled access to a non-natural congener (5-epi-pinnamine) of the natural product. Intramolecular reaction of an N-acyl iminium ion was a key step in the synthesis of both pinnamine and anatoxin-a. However, in stark contrast to literature precedent, complete racemization was observed during the reaction of the N-acyliminium ion leading to the latter alkaloid.

(E)-beta-Trialkylstannyl-alpha,beta-unsaturated ketones are readily available from secondary propargylic alcohols via a two-step sequence involving highly regio- and stereoselective Pd(0)-catalyzed hydrostannation followed by mild oxidation (TPAP). The methodology has been applied to the synthesis of enantiomerically pure enone 12 which is a key intermediate for the total synthesis of zoanthamine, a structurally complex marine natural product.

L'alcaloide spiranique du titre est synthetise regio-, stereo- et chimioselectivement a partir de l'ether de benzyle et de cyclohexadiene-1',2'yl-4 butyle via des reactions catalysees par Pd(OH) 2 ou Pd(O Ac) (Ac=acetyl)