Acyl transfer ketene

The preparation of stereochemically enriched compounds by asymmetric acyl transfer in a stoichiometric sense can be divided into two broad classes [1] (1) those in which a racemic or achiral /weso nucleophile reacts diastereoselectively with an enantiomerically highly enriched acyl donor (Type I, see below) and (2) those in which an enantiomerically highly enriched nucleophile reacts diastereoselectively with a racemic or achiral/meso acyl donor (Type II, see below). When a racemic component is involved, the process constitutes a kinetic resolution (KR) and the maximum theoretical yield of diastereomerically pure product - given perfect diastereoeselectivity - is 50%. When an achiral/meso component is involved, the process can constitute a site-selective asymmetric desymmetrization (ASD) or, in the case of 7r-nucleophiles and reactions involving ketenes, a face-selective addition process and the maximum theoretical yield of diastereomerically pure product - given perfect diastereoselectivity - is 100% (Scheme 8.1). 

Similarly, the acyl transfer from the resin /3-keto ester (9) (R = CH2C02Et and R = CH2COCH3) was supposed to take place via the intermediate formation of a ketene. Although the formation of ketene could not be demonstrated in this reaction, it could still be trapped on the amine-resin. The formation of a ketene as an acylating species was assumed by analogy to Bruice s EjcB reaction (Holmquist and Bruice, 1969). 

Another valuable derivatization was realized via the treatment with A,C)-dimethylhydroxylamine under pyridone catalyzed acyl transfer conditions, followed by reduction with Zn(OTf>2/NaBH4, giving Weinreb amide 105 in 99% ee and 46% yield over three steps from ketene 89 (Scheme 3.22). 

The acyl-alkv biradical obtained by ring-opening of a cyclic ketone is able lo undergo intramolecular disproportionation in one of two ways. A hydrogen atom may be transferred to the acyl radical from the position adjacent to the alkyl group, and this produces an unsaturated aldehyde (4.21). Alternatively, a hydrogen may be transferred to the alkyl radical from the position adjacent to the acyl group, and this results in the formation of a ketene (4.22). Many ketenes are labile, and the use of a nucleophilic solvent or addend. 

The scheme proposed for the reaction over HFAU was that PA dissociates in phenol (P) and ketene and that o-HAP, which was highly favoured over the para isomer, results partly from an intramolecular rearrangement of PA, partly from acyl group transfer from PA to P whereas p-HAP results from this latter reaction only. In these experiments, the zeolite deactivation was very fast, as a result of coke deposition and zeolite dehydroxylation. Catalyst stability can be considerably improved by operating at lower temperatures and especially by substituting equimolar mixtures of PA and water or P and acetic acid for PA. Much higher HAP yields were obtained by using the P - acetic acid mixture as reactants.[68]... 

This technology has been apphed as part of the total synthesis of myx-alamide A (Scheme 56) [139]. The stereoselective aldol reaction between aldehyde 218 and the propionate 219 dehvered, after reduction, protection, and acylation, ester 220 as a single isomer. After -silyl ketene acetal formation a [3,3]-sigmatropic rearrangement accompanied by 1,3-chirality transfer took place. This, together with the uniform prochirality at the double bonds of the... 

This reaction was first reported by Mukaiyama et al. in 1974. It is a Lewis acid-catalyzed Michael conjugate addition of silyl enol ether to o ,/3-unsaturated compounds. Therefore, it is generally referred to as the Mukaiyama-Michael reaction. Because this reaction is essentially a conjugate addition, it is also known as the Mukaiyama-Michael addition or Mukaiyama-Michael conjugate addition. This reaction is a mechanistic complement for the base-catalyzed Michael addition, j and often occurs at much milder conditions and affords superior regioselectivity. s Besides silyl enol ether, silyl ketene acetals are also suitable nucleophiles in this reaction.For the hindered ketene silyl acetals, the Lewis acid actually mediates the electron transfer from the nucleophiles to o ,/3-unsaturated carbonyl molecules.On the other hand, the Q ,j8-unsaturated compounds, such as 3-crotonoyl-2-oxazolidinone, alkylidene malonates, and a-acyl-a,/3-unsaturated phosphonates are often applied as the Michael acceptors. It has been found that the enantioselectivity is very sensitive to the reactant structures —for example, Q -acyl-Q ,j8-unsaturated phosphonates especially prefers the unique syn- vs anft-diastereoselectivity in this reaction. In addition,... 

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