Claisen ester-enolate

Ireland ester-enolate Claisen. Aidhchirnica Acta 1993, 26, 17. 

Ester Enolate Claisen- 4 carbon ring contractions... 

This effect is the basis of the synthetic importance of ester enolate Claisen rearrangements in which enolates or silyl enol ethers of allylic esters are rearranged into 4-pentenoate esters. 

When ethyl trifluoroacetylacetate is treated with an allylic alkoxide, tran-sesterification is followed by ester enolate Claisen rearrangement m a process that on decarboxylation yields stereospecifically the tnfluoromethyl ketone product [22] (equation 19)... 

CHCI3, reflux (Ireland ester enolate Claisen rearrangement)... 

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]. 

Selective protection of the primary alcohol gave 138 (P=TBDMS), which was then esterified with ( )-3-hexenoic acid to produce the key intermediate 139 for cyclization. Ireland ester-enolate Claisen rearrangement and hydrolysis produced a protected hydroxyacid, which, after reduction of the acid and deprotection of the alcohol, yielded meso diol 128 more quickly and efficiently than in the previous synthesis. The meso diol was then converted to the racemate of the lactol pheromone 130 as previously described. 

In one final improvement to the synthesis of the racemate, after it had been shown that even the unnatural enantiomer of the pheromone attracted bugs, the Z-isomer of diene ester 139 was used in the ester-enolate Claisen rearrangement, resulting in a slightly higher yield, and avoiding the use of HMPA as a solvent in that step [113]. 

The stereoselectivity of ester enolate Claisen rearrangements can also be controlled by specific intramolecular interactions.168 169 The enolates of a-alkoxy esters give the Z-silyl derivatives because of chelation by the alkoxy substituent. 

The full paper on the synthesis of onikulactone and mitsugashiwalactone (Vol. 7, p. 24) has been published.Whitesell reports two further useful sequences (cf. Vol. 7, p. 26) from accessible bicyclo[3,3,0]octanes which may lead to iridoids (123 X=H2, Y = H) may be converted into (124) via (123 X = H2, Y = C02Me), the product of ester enolate Claisen rearrangement of the derived allylic alcohol and oxidative decarboxylation/ whereas (123 X = 0, Y = H) readily leads to (125), a known derivative of antirride (126) via an alkylation-dehydration-epoxi-dation-rearrangement sequence. Aucubigenin (121 X = OH, R = H), which is stable at —20°C and readily obtained by enzymic hydrolysis of aucubin (121 X = OH, R = j8-Glu), is converted by mild acid into (127) ° with no dialdehyde detected sodium borohydride reduction of aucubigenin yields the non-naturally occurring isoeucommiol (128 X=H,OH) probably via the aldehyde (128 X = O). ... 

The chelated ester enolate Claisen rearrangement of allylic glycinates 9 is carried out with zinc(II) chloride, which is added to the enolate at — 78 C (Table 19). The rearrangement occurs as the reaction mixture is allowed to warm to room temperature over 1 hour. The 2-amino-3,3-difluoro-4-[(2-methoxyethoxy)methoxy] alk-4-enoic acids 10 arc converted directly into the corresponding methyl esters, which can be hydrolyzed to the methyl 2-amino-3,3-difluoro-4-oxoal-kanoates. 

Table 19. Synthesis of 2-Amino-3,3-difluoro-4-[(2-methoxyethoxy)meth-oxy]alk-4-cnoic Acids 10 by the Chelated Ester Enolate Claisen Rearrangement of Allylic Glycinates 943...

The ester enolate Claisen rearrangements of amino acid propargylic esters (106) have been used137 to produce a-allenic amino acids (107), and y, d-un saturated amino acids... 

Ireland ester-enolate Claisen. Aldrichimica Acta 1993 26 17... 

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). 

H.-J. Altenbach, Ester Enolate Claisen Rearrangements , in Organic Synthesis Highlights (J. Mulzer, H.-J. Altenbach, M. Braun, K. Krohn, H.-U. ReiBig, Eds.), VCH, Weinheim, New York, 1991, 116-118. S. Pereira, M. Srebnik, The Ireland-Claisen Rearrangement, AldrichimicaActa 1993, 26, 17-29. 

Stereoselective synthesis of functionalized carbocyclic and heterocyclic compounds via tandem ester enolate Claisen rearrangement/RCM has been reported (Eq.79) [131,132],... 

Ester enolate Claisen rearrangement (4, 307- K)8 6, 276-277 7, 209-210). Lithium hexamethyldisilazide is comparable to LDA in combination with HMPT for stereoselective Claisen rearrangement of ester cnolates. ... 

A clever application of the ME rearrangement, this time including its stereochemical potential, was developed by Heathcock [133]. The concatenation of an asymmetric aldol reaction [134-136], an ester-enolate Claisen rearrangement [137,138], and a ME reaction allow for the stereoselective generation of a 1,2,5-stereotriad. 

Several factors contribute to the versatility of the ester enolate Claisen rearrangement. Among these are the ability to use a stoichiometric combination of the alcohol and the acid components, the relatively low temperature - of the pericyclic process that allows for the assembly of complex, highly functionalized structures, and the transformation of a carbon-oxygen into a carbon-carbon bond that lends itself easily to the assembly of contiguous quaternary centers. - ... 

As the ester enolate Claisen rearrangement allows for a stoichiometric combination of alcohol and acid components, it has been used for the formation of strategically important C—C bonds by esteriflcation or lactonization and subsequent rearrangement, such as is elegantly demonstrated in the synthesis of the antibiotic chlorothricolide (Scheme 24)." Radical decomposition of the selenoester of (132) leads to... 

Excellent experimental technique was required to effect formation of the monensin cA> ring system (218) via silyl ester enolate Claisen rearrangement of acid (216) and alcohol (217) (Scheme 42). Ester... 

Figure 3 Qualitive effect of C-6-caibon and C 6-oxygen substituents on the transition sute energy of the ester enolate Claisen rearrangement...

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