Stereochemical Puzzle

Treatment of l,l,l-trichloro-2-penten-4-one with aqueous sodium hydroxide solution gives a good yield of 5-chloro- trans-2- cis-4-pentadienoic acid after standard acid work up. 

Suggest a mechanism for this transformation. (Note the original investigators were unable to account satisfactorily for the observed stereochemistry.) 

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Pending solution of the stereochemical puzzle of (82) versus (83), Berson and Nelson (1967) have founda [1,3] sigmatropic reaction, which appears to proceed suprafacially with inversion. They point out that,... 

Mukhopadhyay P, Wipf P, Beratan DN (2009) Optical signatures of molecular dissymmetry combining theory with experiments to address stereochemical puzzles. Acc Chem Res... 

Saa, J. M., Ballester, P., Deya, P. M., Capo, M., Garcias, X. Metal-Induced Reductive Cleavage Reactions An Experimental and Theoretical (MNDO) Study on the Stereochemical Puzzle of Birch and Vinylogous Birch Processes. J. Org. Chem. 1996, 61,1035-1046. 

Birch and associates did not record optical rotation data for natural or semisynthetic brevianamide B and this oversight later proved to constitute the basis of an intriguing stereochemical puzzle the complete stereochemical elucidation of brevianamide B will be discussed below. 

One of the great scientific puzzles is the understanding of enzymic reactions in terms of enzymic structure [1]. To solve the puzzle, and describe in detail the interactions between enzymes, substrates, cofactors and products, requires a description of the three-dimensional structures of the various components, separately and in combination, during all phases of the reaction. Within the past few years, precise three-dimensional stereochemical information has become available for several enzymes, primarily as a result of sequence determination and X-ray crystallography. In some cases, this information now extends to combinations between an enzyme and its substrate(s) and/or cofactor(s). 

An ancient puzzle, immediately addressed by the previous conclusion concerns intramolecular rearrangements that appear unlikely on stereochemical grounds. The most daunting of these is the uncoiling of double-stranded DNA and the related folding of proteins. 

It is important to emphasize at this point that the stereochemical outcome of hydrolyses by epoxide hydrolases is, in theory, somewhat more complicated to analyze than a normal ester hydrolysis for example. This is due to the fact that, for a racemic substrate, each of the two enantiomers can of course react with different kinetics but also different regioselectivities, leading, in certain cases, to quite puzzling results. This problem, which may lead to erroneous interpretations as well as to wrong E value calculations, has been addressed by the two groups mentioned above [176, 177]. A detailed description of such different stereochemical outcomes, as well as of a new method allowing for the determination of the regioselectivity of the enzymatic attack on both enantiomers, has been described very recently [ 178]. 

Cycloadditions of nitrosobenzenes with simple carbocyclic 1,3-dienes have been known for many years.Ib 4 In a recent investigation, Kresze et al. have added p-chloronitrosobenzene to some 5,6-difunctionalized 1,3-cyclohexadienes (Scheme 3-VI).15 In the first example shown, only one cycloadduct was produced, although it is not obvious why this is the case. Also puzzling is the stereochemical result of the second example shown in the scheme. Based on Hart s work (Scheme 3-IV), one might have expected the sy/i-hydroxyl isomer to be the major product of this reaction. 

Several puzzling entries in Table 14 remain to be explained, including reactions where hydroxylic solvents or alkoxide bases are used (entries 11-14). Betaine reversal was demonstrated under hydroxylic conditions in the original Trippet-Jones experiment (Scheme 4) (13), and it is conceivable that interconversion between oxaphosphetanes and betaines could be fast enough in hydroxylic solvents to allow significant betaine reversal to the ylide and aldehyde in some cases. However, there is no clear evidence to implicate stereochemical equilibration of benzylide-derived Wittig intermediates in ether solvents. 

An indication of the strict requirement for yyn-carbopalladation and syti-decarbopalla-dation can be seen in a complete and initially puzzling stereochemical inversion observed in an apparent endocyclic carbopalladation reaction shown in Scheme... 

These stereochemical observations puzzled chemists for many years, until Woodward and Hoffmann developed their theory describing conservation of orbital symmetry. This single theory is capable of explaining all of the observations. We will first apply this theory to explain the stereochemical outcome of electrocyclic reactions taking place under thermal conditions, and then we will explore electrocychc reactions taking place under photochemical conditions. 

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