Crotyl propionate

Ireland demonstrated that the anti 2,3-dimethyl pentenoic acid isomer could be obtained either by rearrangement of the -silyl ketene acetal of -crotyl propionate or with the Z-silyl ketene acetal of the Z-crotyl propionate at comparable levels of diastereoselectivity (Scheme 4.16) [1]. The analogous results for the syn pentenoic acid can be obtained using the Z-silyl ketene acetal of silyl ketene acetal with Z-crotyl propionate. The diastereoselectivities varied from 5 1 to 8 1. Since the allyl silyl ketene acetals are achiral, the products are of course racemic. 

Combining the concepts illustrated in Schemes 14 and 17 leads to the conclusion that use of a chiral non-racemic 2" alcohol will enable the transfer of chiralily from the carbinol center to the newly formed stereocenter(s) at C2 and/or C3 of the pentenoic add product The first example of this type of rearrangement was reported by Ireland in which he employed a C4 TBS crotyl propionate as a chiral T alcohol equivalent (Scheme 4.20) [23]. This example also illustrates how the 1,2-shift of the alkene can alter functional group reactivity, i.e., the allyl silane in the reactant is converted to a vinyl silane in the product. The e s of the pentenoic acid products were not reported. 

To date the most general chiral auxiliary mediated asymmetric Ireland-Claisen rearrangement is that of Corey et al. (Scheme 4.44) [47]. They found that treatment of crotyl propionates and related esters afforded good yields, diastereoselectivities and enantioselectivities of the pentenoic acid products. The rearrangements also occurred at significantly lower temperature than the silyl ketene acetals. A key advantage of the chemistry is that the chiral auxiliary attachment, Ireland-Claisen rearrangement, and auxiliary removal all occur in one pot. 

Exchange with asymmetrical esters, crotyl propionate and 3-buten-2-yl propionate, shows that two reactions take place. One is exchange with isomerization of crotyl ester to 3-buten-2-ol ester, as expected for the acetoxypalladation mechanism. The other is isomerization without exchange ... 

This tandem intramolecular silylformylation/Sakurai reaction has successfully been applied in a formal total synthesis of mycoticin A [75]. The scope and utility of these reactions was expanded to (Z)- and (E)-crotyl groups leading to the stereospecific incorporation of both anti and syn propionate units into the growing polyol chain (Scheme 21) [76]. 

Notably, the rate increase for the Claisen rearrangement of methoxyallyl propionate is only about a factor of 3 over the parent crotyl system, compared to a factor 10 for the pyranoic glycals, cf. refs. 178 and 211. 

Lewis acids such as SnBr4 promote the coupling of 4-acetoxy-l,3-dioxanes with cro-tyl-metal species to generate propionate motifs (Eq. 40) [67]. The reactions show a marked dependence on Lewis acid, crotyl metal species, and the presence and stereochemical disposition of a C5 methyl group. A 1,3-syn methyl relationship is favored in these additions. 

Asymmetric allylation and crotylation, synthetically equivalent to the aldol reaction, have been extensively studied and have become a very useful procedure for preparation of propionate units. Among various chiral ligands on boron-developed, isopinocampheyl- and tartrate-derived reagents, 51 and 52, which were developed by Brown et al. [18] and Roush et al. [19], respectively, are the most commonly used (Scheme 7). Reaction of aldehyde with (Sl-Sla or 52a gave anu -adduct 54, while that using (Z)-51b or 52b afforded syn-adduct 53 with high asymmetric selectivity. 

The allylation and crotylation of aldehydes provide attractive alternatives to asymmetric acetate and propionate aldol addition reactions for the construction of /1-hydroxy aldehydes or ketones (Scheme 5.2 see also Chapter 4). In analogy to propionate aldol addition reactions, an important stereochemical feature involving the addition of substituted allylation reagents to aldehydes is simple diastereoselectivity namely, the formation of 1,2-syn versus 1,2-anti products. Although the underlying reasons for absolute and relative induction have yet to be studied in mechanistic detail for many of these processes, there are a collection of methods that reliably and predictably furnish optically active adducts. 

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