Selectivity Torquoselectivity

Trialkylsilyl vinyl ketenes (72) have been shown to react stereoselectively with a-benzotriazolyl organolithium species to give highly substituted cyclopentenones. The selectivity was found to be kinetic, not thermodynamic, in origin. Several possible mechanisms have been proposed (Scheme 10). It has been suggested that the observed stereoselectivity may result from torquoselectivity in a concerted reaction, or from stereospecific conrotatory cyclization of cation (73), formed stereoselectively because of the interaction shown between the electron-withdrawing group Z and the metal ion.75... 

When asked to name his most important scientific discovery, Houk first names, as a single discovery, his development of FMO explanations of selectivity in pericyclic reactions, most notably expressed in the idea of torquoselectivity. Houk believes that more important has been the general impact his research has had on science. Our work has helped establish computational methods as a real strong partner with experiment, he says. His claim to fame, be believes, is that he s the synthetic chemist s go-to-guy when it comes to computations. ... 

The mechanism of olefination can be deduced by consideration of orbital interactions to proceed via torquoselective olefination, rather than chelation control, for the following reasons (1) the sterically hindered siloxy and phenoxy groups are also effective for high -induction (2) in the presence of a crown ether, the selectivity still remains high and (3) an axially oriented siloxy group induces a high Z-selectivity. Theoretical calculations indicate that the transition state of inward rotation is stabilized by an orbital interaction between a(C-O) and ct (C-OR) (157) . 

Denmark and co-workers reported a good example of torquoselection in the silicon-directed Nazarov cyclization (see Section 3.4.5.1). They demonstrated that cyclohexenyl-derived divinyl ketones 26 cyclize to give the relative stereoisomer 27 as the major product (see Section 3.4.5.1 for the mechanism of the silicon-directed reaction). The use of bulky alkyl groups (such as /-butyl) and/or bulky silicon substituents gave the best selectivity, at the expense of the chemical yield. It is interesting that the corresponding cyclopentenyl-derived systems gave only poor torque-selectivity. 

As with many asymmetric processes, there are three ways to control absolute stereochemistry in the Nazarov cyclization Asymmetry transfer, the use of chiral auxiliaries, or asymmetric catalysis. It is important to realize, however, that there are two distinct processes operating that determine the stereochemistry of the product. To control the absolute stereochemistry of the p-carbon atom(s), it is necessary to control the sense of conrotation, clockwise or counterclockwise (torquoselectivity, see Section 3.4.3). To control the absolute stereochemistry of the a-carbon atom however, it is necessary to control the facial selectivity for enol protonation. 

In contrast, the C-C triple bond shows excellent effect on torquoselectivity. Alkynyl aUcyl ketones 81 are olefinated by ynolates to afford the tetrasubstituted olefins 83 in good -selectivity (Fig. 28) [72]. In the electrocyclic reaction of 82, the alkynyl group prefers outward rather than inward rotation over the alkyl and alkenyl... 

The ( )-p-alkoxy divinyl ketones 129, potential Nazarov reaction precursors, are prepared according to the torquoselective olefination methodology with ynolates (Fig. 45). For example, ethyl 3-phenylpropionate (127) is olefinated by the ynolate to afford the p-alkoxy-ot,p-unsaturated acid 128 with high -selectivity. The acid 128 is converted into the Weinreb amide, which is subjected to alkenylation to provide the p-alkoxy divinyl ketone 129 in good overall yield. 

A silyl-substituted ynolate 141 undergoes cycloaddition to A-sulfonyl aldimines 142, followed by ring opening, to afford the a,p-unsaturated amide 143 at 20 °C (Fig. 52) [39]. This stereoselectivity is unexpected for the torquoselective olefination. The steric interaction between bulky MeaSi and the phenyl groups may be critical. A-o-Methoxyphenylaldimines 144 with ynolates at room temperature produce a,(3-unsaturated amides 145 in good yield with high -selectivity (Fig. 53) [122], Since the double adduct 146 is produced as an intermediate, the process involves the retro-Mannich reaction. 

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