Aldol group transfer

Webster, O. W. andD. Y. Sogah, Group Transfer and Aldol Group Transfer Polymerization, pp. 163—169 in Comprehensive Polymer Science, Vol. 4, G. C. Eastmond, A. Ledwith, S. Russo, and P. Sigwalt, eds., Pergamon Press, London, 1989. 

If the living ROMP of norbomene is terminated with a 9-fold excess of terephthalaldehyde, the chains formed carry an aldehyde end-group which, when activated by ZnCl2, can be used to initiate the aldol-group-transfer polymerization of tert-butyldimethylsilyl vinyl ether621. 

Aldol group transfer polymerization of ferf-butyldimethylsilyl vinyl ether [62] was initiated by pendant aldehyde functions incorporated along a poly(methyl methacrylate) (PMMA) backbone [63]. This backbone was a random copolymer prepared by group transfer polymerization of methyl methacrylate (MMA) and acetal protected 5-methacryloxy valeraldehyde. After deprotection of the aldehyde initiating group, polymerization proceeded by activation with zinc halide in THF at room temperature. The reaction led to a graft copolymer with PMMA backbone and poly(silyl vinyl ether) or, upon hydrolysis of the ferf-butyldimethylsilyl groups, poly(vinyl alcohol) branches. 

Charleux, B. and Pichot, C. (1993) Styrene-terminated poly(vinyl alcohol) macromonomers. 1. Synthesis by aldol group transfer polymerization. Polymer, 34, 195. 

More recently the workers at Du Pont have developed aldol group transfer polymerization, in which a silyl vinyl ether is polymerized using an aldehyde as the initiator to give a living silylated poly(vinyl alcohol), e.g. 

This chapter will begin with a discussion of the role of chiral copper(I) and (II) complexes in group-transfer processes with an emphasis on alkene cyclo-propanation and aziridination. This discussion will be followed by a survey of enantioselective variants of the Kharasch-Sosnovsky reaction, an allylic oxidation process. Section II will review the extensive efforts that have been directed toward the development of enantioselective, Cu(I) catalyzed conjugate addition reactions and related processes. The discussion will finish with a survey of the recent advances that have been achieved by the use of cationic, chiral Cu(II) complexes as chiral Lewis acids for the catalysis of cycloaddition, aldol, Michael, and ene reactions. 

The TBS ketene acetal was proposed to be the preferable silyl component, while the rate of the TBS transfer to the aldolate group of the product decreased and did not overtake the slow-acting carbenium catalysis (Scheme 54). 

Mikami has carried out a number of investigations aimed at elucidating mechanistic aspects of this Si-atom transfer process. In particular, when the aldol addition reaction was conducted with a 1 1 mixture of enoxysilanes 60 and 62, differentiated by the nature of the 0-alkyl and 0-silyl moieties, only the adducts of intramolecular silyl-group transfer 63 and 64 are obtained (Scheme 8B2.6). This observation in addition to results obtained with substituted enol silanes have led Mikami to postulate a silatropic ene-like mechanism involving a cyclic, closed transition-state structure organized around the silyl group (Scheme 8B2.6). 

Aldol reactions of both (E)- and (Z)-ketene acetals are highly susceptible to KOBuc catalysis. In the presence of 5 mol% of KOBuc, aldol reactions proceeded to completion within minutes at -78 °C < 1994JA7026>. A double-label crossover experiment, devised to probe the nature of the silicon group transfer in the alkoxide-catalyzed aldol reaction, suggested that free metal enolates are the true reactive species adding to the aldehydes. 

LiC104 was shown to be a more compatible Lewis acid for chelation in an ethereal solvent—when TiCU, a typical chelation agent for a-alkoxyaldehydes, was used in EtaO for alkylation of 79, moderate diastereoselectivity (68 32) was obtained. Rapid injection NMR studies of the TiCU-promoted chelation-controlled Mukaiyama aldol reaction and the Sakurai reaction show that an acyclic transition state must be involved in which the silyl groups never reach the carbonyl oxygen atom. In LPDE-mediated enolsilane additions silylated products predominate. Obviously, the mechanism is different—it is a group-transfer aldol reaction [107]. 

These carbanions can be formed (Figure 5.8) by proton abstraction from ketones resulting in aldol condensations, by proton abstraction from acetyl CoA, leading to Claisen ester condensation, and by decarboxylation of p-keto acids leading to a resonance-stabilised enolate, which can likewise add to an electrophilic centre. It should be noted that the reverse of decarboxylation also leads to formation of a carbon—carbon bond (this is again a group transfer reaction involving biotin as the carrier of the activated CO2 to be transferred). 

A similar conjugate addition- silyl group transfer process was reported later by Danishefsky and co-workers for the synthesis of PGF2a (Scheme 52) (103). In this case, the silyl ketene acetal adds, under Hgl2 promotion, cis to the OTBS group in the optically pure enone 52.1 to provide silyl enol ether 52.2 as the exclusive product. The indicated aldol products are obtained from 52.2 in subsequent reactions with ( )- and (Z)-octenal using TiCl4 catalysis. 

The nucleophilic addition of enol silanes with aldehydes to produce P-silyloxy carbonyl adducts 47 is an example of a group-transfer process (Scheme 2), for applications in polymer synthesis, see [64a, 64b, 64cj. In its simplest mechanistic rendition the reaction proceeds upon coordination of the aldehyde to Lewis acid MX4 to afford an activated electrophilic species 42. Addition of the nucleophilic enol silane 43 to 42 leads to C-C bond formation and generation of the aldol adduct. Various intermediate structures 44,45,46 have been postulated to be formed concomitant with or following C-C bond formation. The generation of intermediates 45 and 46 necessitates subsequent silylation of the P-alkoxide furnishing aldol adduct 47 and regenerating catalyst MX4. 

The aldol addition of butanal is shown in Mechanism 20.1. The enolate is formed in the first step by deprotonation of the a carbon. At this point, the reaction mixture contains both the aldehyde and its enolate. The carbonyl group of the aldehyde is electrophilic the enolate is nucleophilic. This complementary reactivity leads to nucleophilic addition of the enolate to the carbonyl group (step 2). This is the step in which the new carbon-carbon bond forms to give the alkoxide ion corresponding to the aldol. Proton transfer from the solvent (water) completes the process (step 3). The product of the aldol addition of butanal contains two chirality centers however, it is racemic because the reactants are achiral. 

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