Intramolecular retro-Claisen

The effect of the angle change is clearly apparent in an intramolecular retro-Claisen condensation (Scheme 7.2). The free alkyne does not react, other than simple deprotonation, because the 180° bond angle cannot be accommodated within the 7-membered ring intermediate. The complex, however, does react giving the ring-expanded product." ... 

Similar to the mechanism described in Scheme 2.16, a Knoevenagel reac-tion/ketalization cascade of hydroxyacetone with 1,3-dicarbonyl compounds is assumed. In Scheme 2.16, a Knoevenagel condensation/ketalization reaction is depicted. This sequence allows a subsequent oxa-Michael addition, which yields the corresponding C-glycosides. In contrast, a Knoevenagel addition/ketalization occurs under the reaction condition described in Scheme 2.28, which is followed by an intramolecular retro-Claisen step. As a result of that, the corresponding esters were obtained (Scheme 2.29). 

To explain the high selectivity, which is detected in these cascade reactions, the possible products and reaction paths for reaction with L-erythrulose 146 and acety-lacetone 5 are depicted in Scheme 2.32. The stereoselective Knoevenagel addition to intermediate Q is favored and determines simultaneously the configuration of the tertiary alcohol. A subsequent ketalization step to ketone S followed by the final intramolecular retro-Claisen step yields the isolated product 147 as a single stereoisomer. 

In the amine-catalyzed reactions, a Knoevenagel addition/ketalization/ intramolecular retro-Claisen cascade is detected (Scheme 2.32). The retro-Claisen step is enabled by the ketalization of the Knoevenagel addition product Q. The ketalization of the Knoevenagel product (Q S) is initiated by the hydroxyl groups of the carbohydrate moiety, as in-house NMR-experiments suggest (formation of intermediate ketal structure K in Knoevenagel condensation/ketalization/oxa-Michael cascade reaction Scheme 2.16). Products derived from this reaction sequence (Scheme 2.16)... 

Sometimes, aldehydes obtained by TPAP oxidations suffer in situ intramolecular transformations in substrates with a great predisposition to do so. Examples found in the literature include retro-Claisen rearrangements,108 dipolar additions on enals,106a and attack of malonates109 and indole rings11 on aldehydes. 

B as an ester- or lactone-substituted aldehyde enolate. Such enolates undergo condensations with all kinds of aldehydes, including paraformaldehyde. An adduct E is formed initially, acy-lating itself as soon as it is heated. The reaction could proceed intramolecularly via the tetrahedral intermediate D or intermolecularly as a retro-Claisen condensation. In both cases, the result is an acyloxy-substituted ester enolate. In the example given in Figure 13.50, this is the formyloxy-substituted lactone enolate C. As in the second step of an Elcb elimination, C eliminates the sodium salt of a carboxylic acid. The a,/)-unsaturated ester (in Figure 13.50 the 0J,/3-unsaturated lactone) remains as the aldol condensation product derived from the initial ester (here, a lactone) and the added aldehyde (here, paraformaldehyde). 

Addition of lithium enolate (56) to trifluorocrotonate (55) proceeded smoothly in almost quantitative yields with excellent stereoselectivity. The intramolecular chelation in 57 retards the retro-aldol reaction. On the other hand, nonfluorinated crotonate (59) provided 60 in a poor yield because of the faster retro-aldol reaction [26]. The stereochemistry of the chelated intermediate (57) was proven by trapping 57 as its ketenesilylacetal (61). Pd-catalyzed Ireland-Claisen rearrangement of 61 proceeded stereospecifically to give a single stereoisomer (62), suggesting a rigid control of the three consecutive stereocenters (Scheme 3.12) [27]. 

Reviews have appeared on the use of the Wittig reaction in industrial practice, the Claisen rearrangement, synthetic applications of the retro-Diels-Alder reaction, organo-palladium intermediates for the alkylation and arylation of olefins, the Prins reaction to give 1,3-dienes, and intramolecular [4 + 2] (Diels-Alder) and [3 + 2] cycloadditions.An interesting discussion of the regiospecificity of the Diels-Alder reaction in terms of frontier orbital overlap favours the Woodward-Katz concept. Useful alkyne and polyene coupling reactions are described in reviews on the chemistry of vitamin the synthesis of insect sex... 

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