Claisen Rearrangement Diastereoselectivity

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],... 

Nordmann and Buchwald have reported a diastereoselective Claisen rearrangement of an allyl vinyl ether to an aldehyde (Scheme 6.81) [170]. Using N,N-dimeth-ylformamide as solvent, an 80% yield with a diastereomeric ratio of 91 9 was obtained by microwave heating at 250 °C for 5 min. Conventional heating at 120 °C for 24 h provided somewhat higher yields and selectivities (90% yield, dr = 94 6). 

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

Claisen rearrangement of glycolates. Two laboratories 2 have reported that allylic glycolate esters undergo Claisen-Ireland rearrangement (6, 276-277) with useful diastereoselectivity. This rearrangement was used in a synthesis of 1, the aggregation pheromone of the European elm bark beetle.1... 

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],... 

Several applications of this methodology are known. For the determination of the relative configuration of the stereocenter and the axial chiral unit of 71, the product of a diastereoselective ester enolate Claisen rearrangement of 70, with AgBF4 a cycli-zation to 72 was initiated. Then the carboxylic acid was reduced to alcohol 73 and the position of the substituents was investigated by NMR and by the use of NMR shift-reagents (Scheme 15.16) [32], Control experiments ensured the stereospecifi-city of the cyclization and the reduction step. There are further examples of this strategy [33]. 

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. 

Simple Diastereoselectivity 1.2.1. Claisen Rearrangement of Alkynyl Compounds... 

The propynyl Claisen rearrangement constitutes a powerful method for the regio- and diastereoselective synthesis of chiral allenes containing an additional stereogenic center in one of the substituents at the axially dissymmetric propadiene unit. 

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 (panial) description of the synthesis and coupling of the live fragments starts with the cyclohexyl moiety C21—CM The first step involved the enantio- and diastereoselective Sharpless epoxidation of l,4-pentadien-3-ol described on p 126f The epoxide was converted m four steps to a 3-vinyl 6-lactone which gave a 3-cydohexenecarboxylate via Ireland-Claisen rearrangement (cf p 87) Uncatalysed hydroboration and oxidation (cf. p 131) yielded the desired muis-2-methoxycydohexanol which was protected as a silyl ether The methyl car-... 

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