Diastereomeric catalyst-substrate adducts

Figure 1. Diastereomeric catalyst-substrate adducts produced upon addition of olefin to solvated catalyst with chelating diphosphine ligand.

When the diphosphine is chiral, binding of a prochiral alkene creates diastereomeric catalyst-alkene adducts. (Diastereomers result because binding of a prochiral alkene to a metal center generates a stereogenic center at the site of unsaturation.) Through a powerful combination of3lP and l3C NMR methods, Brown and Chaloner first demonstrated the presence of two diastereomeric catalyst-enamide adducts with bidentate coordination of the substrate to the metal (Figure 1) [19]. 

A mechanism involving correlation between the stability of the alter-ligand complex on the catalyst surface containing a chiral ligand and the enantioselectivity of the catalyst appears to be the most acceptable explanation. This is the lock and key mechanism in which enantioselectivity is specified by the first prochiral substrate bonding with chiral catalysts. Another approach to the reaction mechanism is based not on a consideration of the initial triple complex formation but takes into account the high reactivity of the lesser diastereomeric adduct, catalyst-substrate, corresponding to less favorable... 

No other adducts are formed, and the endo/exo diastereomeric ratio is essentially the same for all of these methods. Further, the existence of an acid catalyzed mechanism for cycloaddition can be explicitly excluded by using an excess of a hindered amine base (2,6-di-tert-butylpyridine, DTBP) in the aminium salt induced reaction and by examining the results of an authentic acid catalyzed reaction (using, for example, triflic acid). In the former case, the same endo and exo adducts are formed in virtually the same relative amounts, but in the latter case neither of these adducts is formed. It is worth noting that acid catalyzed reactions have indeed sometimes been observed under typical aminium salt conditions [70], but these have never been observed, nor would they be expected, under PET conditions. Finally, in the instance where cation radicals are generated by the aminium salt method, the intervention of substrate cation radicals can usually be verified by the addition of the reduced form of the catalyst, i.e., the neutral triarylamine, to the reaction mixture. 

In a separate, elegant use of 165, Rychnovsky and coworkers have carried out a diastereoselective addition of methyl acetate-derived silyl ketene acetal to aldehyde 174 to afford adduct 175 in high diastereomeric purity (Scheme 15) [102]. Hydroxy ester 175 was subsequently employed as an intermediate in the total synthesis of the polyene macrolide antibiotic Roflamycoin. This work highlights a novel application of the chiral catalyst system in reagent-controlled coupling of chiral functionahzed substrates which by themselves display only mod-... 

Tin(IV)-chloride-mediated double aldol reaction of acyclic ketones is rendered stereoselective by a chiral phosphine oxide, (5)-BE JAPO it is proposed that the catalyst controls the first aldol and the substrate controls the second. Another chiral diphosphine oxide, this one based on thiophene, catalyses direct aldols in high delee Chiral a-silyloxy ketones derived from lactate (61) undergo titanium(IV)-mediated aldols giving diastereomerically pure syn-syn adducts (62) in high yield, irrespective of the alkyl groups fianking the silyl or carbonyl. 

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