Enantioselective reduction reactions are privileged transformations for the construction of trisubstituted stereogenic centers. While these include established synthetic strategies, such as asymmetric hydrogenation, methods based on the enantioselective addition of hydridic reagents to electrophilic prochiral substrates have also gained importance. In this context, the asymmetric conjugate reduction (ACR) of α,β-unsaturated compounds has become a convenient approach for the synthesis of chiral compounds with trisubstituted stereocenters in α-, β-, or γ-position to electron-withdrawing functional groups. Because such activating groups are diverse and amenable of further derivatizations, ACRs provide a general and powerful synthetic entry towards a variety of valuable chiral building blocks. This Review provides a comprehensive collection of catalytic ACR methods involving transition-metal, organic, and enzymatic catalysis since its first versions dating back to the late 1970s.

Oxidation of p‐XC6H4SOMe (X = NC, F3C) by (alkylperoxo){tris[(2R)‐2‐hydroxy‐2‐phenylethyl]amine}titanium (2b) has been shown to follow Michaelis−Menten kinetics demonstrating the occurrence of an intramolecular nucleophilic oxygen transfer to the TiIV‐coordinated sulfoxide. The reaction of the titanium(IV) precursors 1 with sulfoxides has been studied by ESI‐MS techniques together with ab initio calculations. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Allosteric regulation of protein activity by noncovalent modifiers (ions or neutral molecules) is a feature found in many natural systems including enzymes. [1] The role of these modifiers is to induce conformational changes in the protein that trigger its activity while they are usually not directly involved in the specific function performed by the macromolecule. and 2.5 equiv of SmI 2 ) when, after 30 min, excess SmI 2 was eliminated from the reaction mixture by bubbling a stream of air prior to the hydrolysis.After formation of the alkyl (2E,4E)-2-alkylalka-2,4-dienoate 4, the SmI 2 -promoted 1,4-reduction of the two conjugated CÀC double bonds, which is initiated by oxidative addition of SmI 2 , produces an enolate radical 5, [12] which could explain the observed dimerization at the d-position of compounds 4 a, and 4 e. A second electron transfer from SmI 2 affords an allylic dianion 6 and its hydrolysis with H 2 O or D 2 O produces the corresponding compound 2 (Scheme 1).The observed lower diastereoselectivity in the formation of the CÀC double bond in the synthesis of 2 a and 2 e, neither of which contain a-alkyl substituents, may be explained by assuming that in case of the a-alkylated esters 2 b ± d and 2 f ± i the s-cis conformation of the starting diene is disfavored by steric hindrance produced by the substitution at the a-carbon atom, while the 1,4-reduction of the conjugated CÀC double bonds of 2 a and 2 e takes place through both the s-cis and s-trans conformations. The complete deuteration at C5 instead of at C3 of the dianion 6 could be explained by assuming that in this resonance-stabilized dianion, the 1,4dianion structure is more stable than the 1,2-dianion structure due to the charge repulsions.The proposed mechanism is supported by the fact that the synthesis of compounds 2 can be also carried out starting from the corresponding alkyl (2E,4E)-2-alkylalka-2,4-dienoate 4. Thus, treatment of ethyl (2E,4E)-2-hexylhexa-2,4-dienoate (4 d) with SmI 2 (2.5 equiv) and D 2 O (2 mL) for 30 min at room temperature affords 2 d in 84 % yield.The described methodology can be applied to obtain ddeuterio-b,g-unsaturated esters. The reaction of 2 h with LDA, followed by treatment with H 2 O afforded ethyl (E)-5deuterio-2-methyl-5-phenylpent-3-enoate (8 h) with total diastereoselectivity (89 % yield). Taking into account that the CÀC double bond of d-deuterio-and a,d-dideuterio-b,gunsaturated esters can be easily hydrogenated, [13] the proposed methodology can be used to prepare saturated ddeuterio-and a,d-dideuterioesters, respectively.In conclusion, in the presence of D 2 O, the simple SmI 2promoted elimination/reduction sequence provides an efficient method for synthesizing a,d-dideuterio-b,g-unsaturated esters 2, in which the CÀC double bond is generated with total or high diastereoselectivity, starting from the readily available a-halo-b-hydroxy-g,d-unsaturated esters 1. Experimental SectionGeneral procedure: A solution of SmI 2 (2.3 mmol) in THF (24 mL) was slowly added dropwise, under a nitrogen atmo...

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