Claisen rearrangement diastereoselective reactions

There are a number of powerful synthetic reactions which join two trigonal carbons to form a CC single bond in a stereocontrolled way under proper reaction conditions. Included in this group are the aldol, Michael, Claisen rearrangement, ene and metalloallyl-carbonyl addition reactions. The corresponding transforms are powerfully stereosimplifying, especially when rendered enantioselective as well as diastereoselective by the use of chiral controller groups. Some examples are listed in Chart 20. 

Morken et al. developed a reductive Claisen rearrangement of substituted allyl acrylates. The reaction of ( )-hex-2-enyl acrylate 175 was catalyzed by [Rh(COD)Cl]2 (0.25 mol %) and Me-DuPhos (0.5 mol %) with C MeSiH in benzene at 22 °C to give y,8-unsaturated ester 176 with high diastereoselect-ivity, 11 1 (Scheme 46) [80]. The reaction was carried out on a 10 g scale to provide a 70% yield of 176. This reaction was applied to allylic ester 177 to provide 178, which is a key intermediate in the total synthesis of inos-tamycin [24],... 

Diastereoselective asymmetric thio-Claisen rearrangement has been carried out by the reaction of thioamides with allyllic bromide (Scheme 37).76... 

The Diels-Alder reaction outlined above is a typical example of the utilization of axially chiral allenes, accessible through 1,6-addition or other methods, to generate selectively new stereogenic centers. This transfer of chirality is also possible via in-termolecular Diels-Alder reactions of vinylallenes [57], aldol reactions of allenyl eno-lates [19f] and Ireland-Claisen rearrangements of silyl allenylketene acetals [58]. Furthermore, it has been utilized recently in the diastereoselective oxidation of titanium allenyl enolates (formed by deprotonation of /3-allenecarboxylates of type 65 and transmetalation with titanocene dichloride) with dimethyl dioxirane (DMDO) [25, 59] and in subsequent acid- or gold-catalyzed cycloisomerization reactions of a-hydroxyallenes into 2,5-dihydrofurans (cf. Chapter 15) [25, 59, 60],... 

Asymmetric allylic C-H activation of more complex substrates reveals some intrinsic features of the Rh2(S-DOSP)4 donor/acceptor carbenoids [135, 136]. Cyclopropanation of trans-disubstituted or highly substituted alkenes is rarely observed, due to the steric demands of these carbenoids [16]. Therefore, the C-H activation pathway is inherently enhanced at substituted allylic sites and the bulky rhodium carbenoid discriminates between accessible secondary sites for diastereoselective C-H insertion. As a result, the asymmetric allylic C-H activation provides alternative methods for the preparation of chiral molecules traditionally derived from classic C-C bond-forming reactions such as the Michael reaction and the Claisen rearrangement [135, 136]. 

The Claisen rearrangement of allyl vinyl ethers is a classic method for the stereoselective synthesis of y,J-unsaturated esters. The allylic C-H activation is an alternative way of generating the same products [135]. Reactions with silyl-substituted cyclohexenes 197 demonstrate how the diastereoselectivity in the formation of 198 improves (40% to 88% de) for the C-H insertion reactions as the size of the silyl group increases (TMS to TBDPS) (Tab. 14.14). Indeed, in cases where there is good size differentiation between the two substituents at a methylene site, high diastereo- and enantioselectivity is possible in the C-H activation. 

Chiral Substrates with Other Achiral Reagents Diastereoselective Claisen Rearrangement and Wittig Reactions... 

Ireland-Claisen rearrangement as an alternative approach to the syn isomer with a high degree of diastereoselectivity was also examined. This reaction might be similar to the system of ester-enolate [2,3]-Wittig shift in the case of OR (R=protective group). 

Diastereoselective aza-Claisen rearrangement,1 The oxazole 1 prepared by reaction of L-valinol with propionic acid is readily convertible into an N-allylketene acetal (2), which rearranges at 150° to 3 in 94% de and 80% overall chemical yield. Acid catalyzed hydrolysis of 3 gives (R)-( - )-2-methyl-4-pentenoic acid (4) (85% yield) with recovery of L-valinol. 

The arylsulfonyl carbanion accelerated Claisen rearrangement is completely regioselective and has also been found to be highly diastereoselective (Scheme 2). The stereochemical course of the reaction conforms to the familiar chair-like transition state model usually invoked for the classic thermal process. Recently, high degrees of asymmetric induction have been observed in tlie rearrangements of chiral cyclic phosphoramidate stabilized carbanion derivatives. ... 

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