Claisen rearrangement stereochemical control

Ireland, R E, Mueller, R H, Willard, A K, Ester enolate Claisen rearrangement — stereochemical control through stereoselective enolate formation, J. Am. Chem. Soc., 98, 2868-2877, 1976. 

If the allylic system is substituted, several isomeric products can be formed. Assuming a chair-like transition state, the stereochemical outcome of a metallo-Claisen rearrangement is controlled by the geometries of the vinyl and allyl moieties, so that, if the vinyl part 68 is stereochemically pure, three different products, syn/anti-73 or 74, can be formed, depending on the exact nature of the active allylic part 72 (Scheme 6)38. 

The versatility of the Claisen rearrangement for the synthesis of functionally substituted y, 8-unsaturated carbonyl compounds has been greatly enhanced by the introduction of various vinyl ether appendages. These not only participate in the stereochemical control of the rearrangement, but also determine the nature of the functional group in the product (-CHO, -COR, -COOH, -COOR, -CONR2). 

Another unprecedented stereochemical control in a Claisen rearrangement was reported recently by Yamamoto using organoaluminum reagents (Scheme 59). Sometimes (e.g. with R = Cu2CH==CH— CsHi i) complete reversal of double bond geometry could be achieved simply by modifying the bulky aluminum catalyst. 

Ireland, R. E., Wipf, P., Xiang, J. N. Stereochemical control in the ester enolate Claisen rearrangement. 2. Chairlike vs boatlike transition-state selection. J. Org. Chem. 1991, 56, 3572-3582. 

TBS-protection, a second, boron-mediated, syn aldol reaction led to the formation of 277 with 95% ds. In this case, ketone 278 controlled the stereochemical outcome of the reaction, and chiral ligands on boron were not required. A simple steric model accounts for this selectivity (see Scheme 9-11), and a titanium-mediated aldol reaction would be expected to give the same product. Following elaboration, including an Ireland-Claisen rearrangement, aldehyde 279 was prepared. 

The Simmons-Smith cyclopropanation reaction Stereochemically controlled epoxidations Regio- and Stereocontrolled Reactions with Nucleophiles Claisen-Cope rearrangements Stereochemistry in the Claisen-Cope rearrangement The Claisen-Ireland rearrangement Pd-catalysed reactions of allylic alcohols Pd-allyl acetate complexes Stereochemistry of Pd-allyl cation complexes Pd and monoepoxides of dienes The control of remote chirality Recent developments Summary... 

The geometry of the vinyl ethers is one important factor that determines the stereochemical outcome of the rearrangement. The vinyl ether geometry strongly depends on the variant employed. Furthermore, the transition-state structures are paramount to the stereochemistry of Claisen rearrangements. The transition state geometry is controlled by both steric and electronic features of the Claisen system. 

With respect to the stereochemical course of the acetylene Claisen rearrangement, problems arise with control of the vinyl ether double-bond geometry. High selectivity should be observed in the rearrangement of cyclic substrates 6. However, the stereochemistry of the products were not reported in this case670. 

Stereochemical control of enolization of esters. In continuation of studies on the Claisen rearrangement of allyl esters (4, 307-308), Ireland and Willard have observed that the stereochemistry of enolization of these esters (1) and (2) can be controlled to a marked extent by the solvent used. Thus Claisen rearrangement of (1) through the enolate obtained in THF alone gives the acids (3) and... 

The Claisen rearrangement of disubstituted allyl vinyl ether 24 was expected to proceed via to a chair-like transition state D because of favorable less-hindered geometry (Eq. 3.1.28) [35]. The importance of the favorable steric control elements found in D to the excellent stereochemical complementary can best be emphasized by comparison with the rearrangement of 26 bearing the E allyl ether under the same reaction conditions as that of 24 (Eq. 3.1.29). In this case, 25% of the aldehydic product mixture arises by way of boat-like transition state E because it is rather less crowded than F. 

The Claisen rearrangement has been used to prepare j8,y-unsaturated amides, largely as the E-isomers, from 3-(trimethylsilyl)allyl alcohols and amide acetals (Scheme 48). Overall yields and stereoselectivities are excellent. Conditions have been found under which the stereochemical outcome of the related ynamine-Claisen rearrangement can be controlled. Thus, the kinetically favoured intermediate is the E-enamine (140) which leads to the "trans product (142), whereas the Z-isomer (141) is thermodynamically favoured and gives the cw ... 

Allylic esters of peptides have been shown to undergo Claisen rearrangement after deprotonation in the presence of tin chloride to afford allylated peptides. Subsequent iV-allylation and ring closure provided the corresponding cyclic peptides. The same authors have made attempts to use the chiral backbone of a given peptide to control the stereochemical outcome of its modification using a chelate-enolate Claisen rearrangement. 

Maruoka K, Nonoshita K, Banno H, Yamamoto H (1988) Unprecedented stereochemical control in the Claisen rearrangement of allyl vinyl ethers using organoaluminum reagents. 

Bartlett, P. A. Hahne, W. F. Stereochemical Control of the Ynamine-Claisen Rearrangement J. Orjf. Chem. 1979, 44, 882-883. 

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