Conjugate substrate-controlled

Burgess and coworkers investigated the hydrogenation of the conjugated diene 87 (Scheme 30.1) [48]. Kinetic studies showed that the reaction occurred mostly stepwise via 2,3-diphenyl-l-butene, while only a small part of the diene was converted directly to 2,3-diphenylbutane, without dissociation of the catalyst from the intermediate mono-alkene. The first hydrogenation step was found to proceed with low enantioselectivity, whereas the second step was characterized by strong catalyst and strong substrate control. 

There appears to exist only one single example of substrate-controlled diastereoselection in the conjugate addition to allenoates7 Base-catalyzed addition of methanol to the steroid allene 11 afforded only one of the two possible diastereomeric products in 95% yield. Unfortunately, the configuration around the exocyclic C —C double bond [( )/(Z)] of 12 was not established7. 

The majority of the reported examples are diastereoselective conjugate additions (Section 7.3.1.). This section has been organized into reactions where the chiral information is located on the nucleophile (Section 7.3.1.1.), on the electrophile (Section 7.3.1.2.), or on both the nucleophile and the electrophile (Section 7.3.1.3.). Further division has then been made, i.e., substrate-controlled vs. auxiliary-controlled diastereoselective reactions, and subdivision according to whether the reactions are inter- or intramolecular in nature. 

Substrate-Controlled Diastereoselective Conjugate Addition to Chiral a,/MJnsaturated Compounds... 

Grignard reagents also add to conjugated substrates such as a,p-unsaturated ketones, cyano-ketones, °° esters, and nitriles, but 1,2-addition may seriously compete The product is often controlled by steric factors. Thus 145 with phe-... 

Addition reactions. Addition of borylsilanes to the triple bond of a conjugated en3fne, catalyzed by Pt(acac)2, is subject to substrate control in that the steric bulk of the terminal substituent exerts an important effect. 

Given aware that previously designed the tandem oxidation/oxa-conjugate addition reaction necessitated no activation of substrates and proceeded in a substrate-controlled manner under neutral, mild reaction conditions, we envisaged that it would be possible to predict the stereochemical outcome of the oxa-conjugate addition reaction through careful conformational analysis of transition states (Figs. 2.4, 2.5). 

Substrate-controlled conjugate additions of oxy-anionic nucleophiles have been reported to proceed with high levels of acyclic stereocontrol [31]. A notable case was disclosed by Mulzer, who studied conjugate additions of alkoxides to the j -substituted acceptor 51 (Equation 8) [71], Addition of methoxide afforded the anti diastereomer 52 in dr =95 5 and 85% yield. 

Polyhedral oligomeric silsesquioxane (POSS) has been extensively studied as starting substrate to construct nanocomposites with precise control of nanoarchitecture and properties. Octahedral derivatives are the most representative ones of this family. It was reported that the HRP-catalyzed conjugation of catechin on amine-substituted octahedral silsesquioxane amplified the beneficial physiological property of flavonoids. The POSS-catechin conjugate exhibited great... 

There are few addition reactions to a,/J-disubstituted enoyl systems 151 that proceed in good yield and are able to control the absolute and relative stereochemistry of both new stereocenters. This is a consequence of problematic A1,3 interactions in either rotamer when traditional templates such as oxazolidinone are used to relieve A1,3 strain the C - C bond of the enoyl group twists, breaking conjugation which results in diminished reactivity and selectivity [111-124], Sibi et al. recently demonstrated that intermolecular radical addition to a,/J-disubstituted substrates followed by hydrogen atom transfer proceeds with high diastereo- and enantioselectivity (151 -> 152 or 153, Scheme 40). 

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