Chair transition state, Claisen rearrangement

The stereochemistry of the silyl enol ether Claisen rearrangement is controlled not only by the stereochemistry of the double bond in the allyhc alcohol but also by the stereochemistry of the silyl enol ether. For the chair transition state, the configuration at the newly formed C—C bond is predicted to be determined by the E- or Z-configuration of the silyl enol ether. 

A biochemically significant Claisen rearrangement is the transformation of choris-mate into prephenate [232] via a chair transition state. Although it is impossible to settle the question of the direction of electron flow during the reorganization, that shown by the arrows in the formula should be preferred when the influence of the various substituents is considered. 

Step b [3,3] sigmatropic shift (ester enolate Claisen rearrangement) via a chair transition state on the sterically more accessible (3-face of the butenolide (B below). 

C-IS in 55% yield (Scheme 53). In this case, the thermal Claisen rearrangement occurred stereospecifi-cally from the a-face of the bicycle, presumably via chair transition state (309) (Scheme 54). Therefore it was concluded that the ortho ester rearrangement occurred predominantly via boat transition state (310), providing the first example of a difference in transition state geometry observed in Claisen variants with the same substrate. 

The only examples of asymmetric Claisen rearrangements catalyzed by a chiral aluminum catalyst are those published by Yamamoto and coworkers [24-27]. The Claisen rearrangement of allyl vinyl ethers of type 91 (Sch. 13) can proceed via either of the two enantiomeric chair transition states 92 or 94. If a chiral Lewis acid is used to activate the process, the transition states become diastereomeric and preferential formation of one enantiomer of the product is possible. This is complicated because coordination of a chiral Lewis acid to the ether oxygen of allyl vinyl ether produces a new chiral center as indicated in 96 and asymmetric induction might occur from a substituent on aluminum to the oxygen and then from the oxygen to the C-3 carbon in the product. In their initial report, Maruoka, Banno, and Yamamoto found that a catalyst prepared from the 3,3 -disilyl-substituted BINOL 97 and trimethylaluminum was effective in this transformation [24]. The catalyst 98 was shown to be monomeric by measurement of freezing point depression. 

The a-substituted 1-methyl allyl vinyl ether was shown to isomerize with a strong preference for the irons product (i.e., 95 % irons, 5 % cfe) . This corresponds to a conformational preference for equatorial methyl (as opposed to axial) in the chair transition state of about 2.4 kcal.mole . The identical value was calculated from the irons product preference in the allyl ester Claisen rearrangements (see a-methyl allyl acetate and a-trifluoromethyl allyl trifluoroacetate). 

Corey and Lee [696] have recently proposed a variant of the Ireland-Claisen rearrangement that uses boron enolates of allylic esters derived from 2.62. The E-crotyi (Re = Me) or E-cinnamyl (Rz = Ph) derivatives could be selectively transformed into the Z- or E-boron enolates 10.46 at low temperature (Figure 10.16). The rearrangements take place at about 0°C, and the Z-enolates lead vay selectively to anti acids 10.47 with an excellent enantiomeric excess while the E-enolates lead to syn acids 10.48, with an interesting selectivity if R = Me or Et (Figure 10.16). In most cases, the enantiomeric excesses are excellent however, when the reaction is conducted with ally] esters (R = H), the ee s are a little bit lower (74 - 84%). These results are interpreted via a chair transition state that minimizes steric interactions [696],... 

If the allenic Claisen substrate is derived from a secondary allenyl alcohol, e.g., 7, the relative configuration of the diastereomeric alcohol determines the geometries of the double bonds of the diene part, and the absolute configuration of the stereocenter at C-2 of the product depends on the absolute configuration of the substrate by 1,4-chirality transfer, provided the rearrangement takes place via a chairlike transition state. Chair transition state A, with the substitutuent R1 equatorial, seems to be preferred because of 1,3-diaxial interactions of R1 with the amide group in transition state B660. 

A significant difference between the Claisen and the Cope rearrangement is that both C-3 and C-4 in the pericyclic carbon framework may be stereogenic centers. The stereochemical outcome of such rearrangements has been demonstrated by the classical investigations on the rearrangement of 3,4-dimethyl-l, 5-hexadienes (32)274. For example, the rearrangement of meso-32 results in the nearly exclusive formation of ( ,Z)-2,6-octadiene (33) via a chair transition state conformation, whereas rac-32 affords a 90 f 0 mixture of the ( , )- and (Z.Z)-iso-mers via chair A and chair B. 

Claisen rearrangement proceeds via a chair-like transition state (584), which was reported to be favored over the boat by 2.5-3.0 kcal moT (10.5-12.6 kJ moT ). 7 jn different work, Houk and co-workers estimated that the chair transition state for this reaction is more stable than the boat transition state by 6.6 kcal mol (27.6 kJ mol ). The synthetic applications of the Claisen rearrangement were reviewed by Ziegler and the stereoselectivity that characterizes this reaction is apparent in those applications. generic Claisen rearrangement is illustrated by heating an allyl vinyl ether such as 585, which rearranges to 586 via chair... 

In their total synthesis of (-i-)-ophiobolin in 1989, Kishi et al. found that treatment of a cyclopentenyl ester under the typical Ireland conditions gave principally C-silylated ester [63]. Heating of a C-silyl ester (prepared by acylation using a C-silyl acyl chloride) at 230 °C resulted in a 1,3-Brook rearrangement followed by an Ireland-Claisen rearrangement to give the desired product as a 6 1 ratio of isomers at C2 of the pentenoic acid (Scheme 4.63). The major product could have arisen through either a chair transition state of the Z-sUyl ketene acetal or a boat transition state of the E-silyl ketene acetal. 

In 1980 Danishefsky et al. reported the first examples of Ireland-Claisen rearrangements of vinyl lactones to afford carbocyclic carboxyUc adds (Scheme 4.89) [82]. Treatment of 6-vinyl pentanoHdes under standard Ireland conditions and heating of the reaction mixture to 105 °C afforded the rearranged adds in generally good yields. The products necessarily arose from a boat transition state, since the chair transition states would be exceptionally strained. 

Compared to 1° and 2° alcohols, 3° alcohol derived allylic esters have received comparatively litde attention as substrates in the Ireland-Claisen rearrangement. This may to some extent reflect difficulty in the synthesis of the requisite i" ester. In addition, stereocontrol in the formation of the resultant alkene may be problematic. The difference in size of the two allyhc substituents is in general large for 2" allyhc stereocenters since one substituent is always H (e.g., R = H, H, Scheme 4.101). However, for 3° aUyhc esters, a smaller size difference will lead to low alkene stereoselectivity. In addition, if there is a lack of differentiation between the two chair transition states, the C2 and C3 stereocenters will be formed in both antipodal forms. 

Rigby et al. employed the Ireland-Claisen rearrangement in an approacdi to the ophiobolane ceroplasteric acid (Scheme4.118) [114]. The product was isolated as a 4 1 mixture of diastereomers at C2 (pentenoic acid numbering). The major product is consistent with rearrangement occurring via a chair transition state for an -silyl ketene acetal or a boat transition state for a Z-sUyl ketene acetal. 

Deslongchamps applied the equatorial selective Ireknd-Claisen rearrangement described previously (cf. Scheme 4.41) in a formal synthesis of erthyronoHde A (Scheme 4.119) [43]. The rearrangement of the Z-silyl ketene acetal proceeded via a chair transition state to establish the C4 and C5 stereocenters of erythronolide A. 

Wilson and Jacob used a y-depro to nation of an allyl acrylate to generate a Z-silyl ketene acetal in a Claisen approach to 25-hydroxy vitamin D2 Grundmann ketone (Scheme 4.121) [115]. The rearrangement proceeded via the expected chair transition state to afford the desired product as a single stereoisomer. 

Kallmerten and Cywin used the glycolate Claisen rearrangement in an approach to zincophorin (Scheme 4.122) [116]. Rearrangement of the Z-silyl ketene acetal of the glycolate ester via a chair transition state afforded the syn stereochemistry in the product The ester was further elaborated to the pyran which constitutes the Cl-Cll subunit of zincophorin. 

Mulzer and Mohr used a glycolate Claisen to establish the C6, C7 stereocenters in an asymmetric synthesis of the asteltoxin Ws-tetrahydrofuran fragment (Scheme 4.127) [121]. Rearrangement occurred via the expected Z-silyl ketene acetal and chair transition state to afford the adjacent carbinol and 4° carbon stereocenters. The high stereoselectivity of the rearrangement using a tetrasubsti-tuted aUyUc alkene is noteworthy. 

Corey et al. used the asymmetric Ireland-Claisen rearrangement in the synthesis of j8-elemene (Scheme 4.131) [124], Rearrangement of the Z-(0)-B-ketene acetal via the chair transition state afforded the trienic acid in good yield with complete diastereo- and enantioselectivity. 

The experimental evidence indicates that in both the Cope rearrangement [18] and the isoelectronic Claisen rearrangement [19], in which one methylene group is replaced by an oxygen atom, reaction via the chair transition state is favored over that via the boat unless the former is prohibited by steric constraints [13]. Although the unconstrained hexadiene molecule can take up either a syn (C2t ) or an anti (C2/1) conformation, its preference for reaction via the chair TS has been repeatedly confirmed by a variety of computational methods [2, 20, 21, 22, 23, 24, 25]. 

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