Rearrangement asymmetric variant

It is known that 5-acyloxyoxazoles 132 rearrange to 4-acyl-5(4/l/)-oxazolones 133 in the presence of 4-(dimethylamino)pyridme or 4-(pyrrohdino)pyridine. Recently, an asymmetric variant of this nucleophUe-catalyzed rearrangement that employs a chiral derivative of 4-(pyrrolidino)pyridine has been described. This procedure allows the construction of quaternary stereocenters with high levels of enantioselectivity (Scheme 7.38). Representative examples of saturated 5(4//)-oxazolones prepared via sigmatropic rearrangements are shown in Table 7.16 (Fig. 7.18). 

An asymmetric variant of this kind of allylic amination, based on their phenylcyclohexanol-derived chiral N-sulfinyl carbamates, was developed by Whitesell et al. (see also Sect. 3.2) (Scheme 34) [85]. After the asymmetric ene reaction with Z-configured olefins (not shown) had occurred, nearly di-astereomerically pure sulfinamides 127 were obtained which were found to be prone to epimerization. Their rapid conversion via O silylation and [2,3]-a rearrangement dehvered the carbamoylated allyhc amines 128 with around 7 1 diastereoselectivity as crystalline compounds that can be recrystallized to enhance their isomeric purity to 95 5. Obviously the imiform absolute configuration at Cl in the ene products 127 was difficult to transfer completely due to the already mentioned ease of epimerization. Unhke the sulfonamides of Delerit (Scheme 33) [84], the carbonyl moiety can easily be cleaved by base treatment. 

An asymmetric variant of this reaction can be carried out introducing a camphor-derived 1-azabutadiene ligand. Enantiomeric excess values of up to 86% can be achieved with this system to obtain planar chiral iron complexes. The photolytically induced reaction of pentacarbonyliron with prochiral cyclohexa-1,3-dienes can also be run enantioselectively using a chiral 1-azabutadiene catalyst. Quantitative yields and ee values up to 86% are possible under these conditions. Cyclic 1,4-dienes can also be complexed by pentacarbonyliron under concomitant rearrangement to the 1,3-diene... 

Under transition metal catalysis, different types of skeletal rearrangement can take place indeed, where the original connectivity along the enyne chain can be maintained or not, as a function of the substrate and the catalyst used [1-4]. High selectivity and efficiency are often realized. The field has been exhaustively reviewed in recent papers [5-8], Surprisingly, asymmetric variants of these reactions [9] are comparatively underdeveloped, in spite of their potential synthetic utility for the construction of chiral cyclic moieties. 

This section will focus on recent examples of asymmetric [3,3]-sigmatropic rearrangements involving dienes and polyenes. Attention will be given to Cope and Claisen rearrangements, as well as to several of their variants. For more exhaustive reviews of the subject, the reader is referred elsewhere69,70. 

Recently, a more versatile enantioselective variant was accomplished by use of the chiral bis(oxazoline) 27 as a chiral coordinating agent . For example, a rearrangement of dibenzyl ether 25 using the premixed complex t-BuLi (2.0 equivalents)/(5, 5 )-27 (1.0 equivalents) in ether at —78 °C afforded 94% yield of alcohol (S)-26 in 62% ee. Furthermore, an asymmetric catalytic version of this rearrangement has been developed (equation 14). This protocol provides the tertiary alcohol 29 with a relatively high % ee from rac-28 (equation 15). 

As a C - C bond-forming process, [2,3]-sigmatropic rearrangements of sulfonium ylides merit particular interest. Indeed, since their discovery in the late 1960s [172-176], this type of yhde rearrangement has become the most extensively studied and applied. This activity is well dociunented in a niunber of excellent review articles, many of them published quite recently [9,177-179]. This demonstrates a vivid interest by the scientific community in these rearrangements which is strongly related to the advent of asymmetric and catalytic variants, as will be discussed later. 

The first asymmetric total synthesis of (+)-astrophylline was accomplished in the laboratory of S. Blechert. The Still variant of the [2,3]-Wittig rearrangement was used to generate the 1,2-trans relationship between the substituents of the key cyclopentene intermediate. The tributylstannylmethyl ether substrate was transmetalated with n-BuLi, which initiated the desired [2,3]-sigmatropic shift to afford the expected homoallylic alcohol as a single enantiomer. 

The most important feature of the Ireland variant is the control of the enolate geometry which allows the internal asymmetric induction (simple diastereoselectivity) of the rearrangement to be controlled (see Section 1.6,3.1.1.4.1.2. p 3412). 

Ortho ester rearrangements also lack control over vinyl double-bond geometry. As a consequence, the reactions proceed without internal asymmetric induction yielding mixtures of diastereomers. Therefore, stereoselective syntheses by the ortho ester variant are often useful only in those cases in which the stereocenter that cannot" be controlled is destroyed in a following step. 

Burke et al. employed a cyclic variant of the glycolate Ireland-Claisen rearrangement in the asymmetric synthesis of (-I-)-breynolide (Scheme 4.128) [122]. The rearrangement of the Z-silyl ketene acetal via a boat transition state generated the C3,C4 stereochemistry of the natural product in high yield and stereoselectivity. 

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