From the 19th century to the present, the complex indole alkaloid strychnine has engaged the chemical community. In this review, we examine why strychnine has been and remains today an important target for directed synthesis efforts. A selection of the diverse syntheses of strychnine is discussed with the aim of identifying their influence on the evolution of the strategy and tactics of organic synthesis.

A broadly useful catalytic enantioselective synthesis of branched allylic esters from prochiral (Z)-2-alkene-1-ols has been developed. The starting allylic alcohol is converted to its trichloroacetimidate intermediate by reaction with trichloroacetonitrile, either in situ or in a separate step, and this intermediate undergoes clean enantioselective S N 2′ substitution with a variety of carboxylic acids in the presence of the palladium(II) catalyst (R p ,S)-di-μ -acetatobis[(η 5 -2-(2'-(4'-methylethyl) oxazolinyl)cyclopentadienyl,1-C,3'-N)(η 4 -tetraphenylcyclobutadiene)cobalt]dipalladium, (R p ,S)-[COP-OAc] 2 or its enantiomer. The scope and limitations of this useful catalytic asymmetric allylic esterification are defined.

The catalytic enantioselective SN2′ displacement of (Z)-allylic trichloroacetimidates catalyzed by the palladium(II) complex [COP-OAc]2 is a broadly useful method for the asymmetric synthesis of chiral branched allylic esters. A variety of experiments aimed at elucidating the nature of the catalytic mechanism and its rate- and enantiodetermining steps are reported. Key findings include: (a) the demonstration that a variety of bridged-dipalladium complexes are present and constitute resting states of the COP catalyst, however, monomeric palladium (II) complexes are likely involved in the catalytic cycle; (b) labeling experiments establishing that the reaction proceeds in an overall antarafacial fashion; (c) secondary deuterium kinetic isotope effects that suggest substantial rehybridization at both C1 and C3 in the rate-limiting step; and (d) DFT computational studies (B3-LYP/def2-TZVP) that provide evidence for bidentate substrate-bound intermediates and an anti-oxypalladation/syn-deoxypalladation pathway. These results are consistent with a novel mechanism in which chelation of the imidate nitrogen to form a cationic palladium (II) intermediate activates the alkene for attack by external carboxylate in the enantiodetermining step. Computational modeling of the transition-state structure for the acyloxy palladation step provides a model for enantioinduction.

Chelated ruthenium catalysts have achieved highly chemoselective olefin metathesis reactions. Terminal and internal Z olefins were selectively reacted in the presence of internal E olefins. Products were produced in good yield and high stereoselectivity for formation of a new Z olefin. No products of metathesis with the internal E olefin were observed. Chemoselectivity for terminal olefins was also observed over both sterically hindered and electronically deactivated alkenes.

2-Vinylchromanes (1), 2-vinyl-1,4-benzodioxanes (2), and 2,3-dihydro-2-vinyl-2H-1,4-benzoxazines (3) can be prepared in high yields (90–98%) and excellent enantiomeric purities (87–98% ee) by [COP-OAc]2-catalyzed cyclization of phenolic (E)-allylic trichloroacetimidate precursors. Deuterium-labeling and computational experiments are consistent with these cyclization reactions taking place by an anti-oxypalladation/syn-deoxypalladation mechanism. 2-Vinylchromanes can be prepared also in good yields and high enantiomeric purities from analogous (E)-allylic acetate precursors, which constitutes the first report that acetate is a competent leaving group in COP-catalyzed enantioselective SN2′ substitution reactions.