Stereochemistry, lead compound thermodynamics

Electrocyclic reactions of 1,3,5-trienes lead to 1,3-cyclohexadienes. These ring closures also exhibit a high degree of stereospecificity. The ring closure is normally the favored reaction in this case, because the cyclic compound, which has six a bonds and two IT bonds, is thermodynamically more stable than the triene, which has five a and three ir bonds. The stereospecificity is illustrated with octatrienes 3 and 4. ,Z, -2,4,6-Octatriene (3) cyclizes only to cw-5,6-dimethyl-l,3-cyclohexadiene, whereas the , Z,Z-2,4,6-octa-triene (4) leads exclusively to the trans cyclohexadiene isomer. A point of particular importance regarding the stereochemistry of this reaction is that the groups at the termini of the triene system rotate in the opposite sense during the cyclization process. This mode... 

This contrary stereochemistry in the Bucherer - Bergs reaction of camphor has been attributed to steric hindrance of e.w-attack of the cyanide ion on the intermediate imine. Normally, equatorial approach of the cyanide ion is preferred, giving the axial (t>Mr/o)-amino nitrile by kinetic control. This isomer is trapped under Bucherer-Bergs conditions via urea and hydan-toin formation. In the Strecker reaction, thermodynamic control of the amino nitrile formation leads to an excess of the more stable compound with an equatorial (e.w)-amino and an axial (endo)-cyano (or carboxylic) function13-17. 

E) alkenes. One explanation for this is that the reaction of the ylid with the carbonyl compound is a 2-1-2 cycloaddition, which in order to be concerted must adopt the [rt2s+n2al pathway. As we have seen earlier (p. 1079), this pathway leads to the formation of the more sterically crowded product, in this case the (Z) alkene. If this explanation is correct, it is not easy to explain the predominant formation of ( ) products from stable ylids, but (E) compounds are of course generally thermodynamically more stable than the (Z) isomers, and the stereochemistry seems to depend on many factors. 

As can be seen, both routes lead to the same product. Nevertheless, in compounds where the conformational flexibility of the bicyclobutane frameworks is restricted, 1,3-addition is found to be favored via the diequatorial mode.12,13 This aspect is illustrated in a reaction in which iodine reacted with tricyclo[4.1.0.02,7]heptane in carbon tetrachloride to give 6,7-diiodobicy-clo[3.1. l]heptane (9) in 55% yield.13 In support of this stereochemistry, the majority of results obtained from the dculeration of tricyclo[4.1.0.02,7]heptane suggested that the attack is from the equatorial position.14 Theoretical studies also support the notion that the equatorial approach of an electrophile to the bridgehead of bicyclo[l.1.0Jbutane is thermodynamically favored.14,15... 

Two independent syntheses of the naturally occurring sulphoxide carpetimycinA (C-19393 H2) have been published 134, 135). A major problem in this series is to obtain the m-stereochemistry of P-lactam protons, while introducing the hydroxyisopropyl substituent at C(6). Most methods of introducing such side-chains lead to the more thermodynamically favoured traws-compounds. Sulphenylation of the oxazine (114) to (168) was followed by the normal aldol reaction with acetone to give (169). 

In this section, methods used in the formation, i.e., the directed production, of centers of asymmetry in the total synthesis of steroids are discussed briefly. A study of this question on the basis of steroid molecules and intermediates in their synthesis consisting of condensed cyclic systems requires a consideration of both "static" stereochemistry, i.e., the comparative thermodynamic stability of cyclic systems, and of dynamic stereochemistry, i.e., the spatial directivity of reactions leading to the formation of centers of asymmetry. The existence of comparatively detailed reviews on the stereochemistry of cyclic compounds [15, 65-67] makes it possible for us not to dwell on general principles of stereochemistry but to restrict ourselves to problems connected with their direct use in total synthesis. 

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