Rearrangement, -sigmatropic stereochemistry

A pericyclic reaction is one that takes place in a single step through a cyclic transition state without intermediates. There are three major classes of peri-cyclic processes electrocyclic reactions, cycloaddition reactions, and sigmatropic rearrangements. The stereochemistry of these reactions is controlled by the symmetry of the orbitals involved in bond reorganization. 

N,O-acetal intermediate 172, y,<5-unsaturated amide 171. It is important to note that there is a correspondence between the stereochemistry at C-41 of the allylic alcohol substrate 173 and at C-37 of the amide product 171. Provided that the configuration of the hydroxyl-bearing carbon in 173 can be established as shown, then the subsequent suprafacial [3,3] sigmatropic rearrangement would ensure the stereospecific introduction of the C-37 side chain during the course of the Eschenmoser-Claisen rearrangement, stereochemistry is transferred from C-41 to C-37. Ketone 174, a potential intermediate for a synthesis of 173, could conceivably be fashioned in short order from epoxide 175. 

In addition to the synthetic applications related to the stereoselective or stereospecific syntheses of various systems, especially natural products, described in the previous subsection, a number of general synthetic uses of the reversible [2,3]-sigmatropic rearrangement of allylic sulfoxides are presented below. Several investigators110-113 have employed the allylic sulfenate-to-sulfoxide equilibrium in combination with the syn elimination of the latter as a method for the synthesis of conjugated dienes. For example, Reich and coworkers110,111 have reported a detailed study on the conversion of allylic alcohols to 1,3-dienes by sequential sulfenate sulfoxide rearrangement and syn elimination of the sulfoxide. This method of mild and efficient 1,4-dehydration of allylic alcohols has also been shown to proceed with overall cis stereochemistry in cyclic systems, as illustrated by equation 25. The reaction of trans-46 proceeds almost instantaneously at room temperature, while that of the cis-alcohol is much slower. This method has been subsequently applied for the synthesis of several natural products, such as the stereoselective transformation of the allylic alcohol 48 into the sex pheromone of the Red Bollworm Moth (49)112 and the conversion of isocodeine (50) into 6-demethoxythebaine (51)113. 

The reaction between o-quinones and electron rich dienes leads to benzodioxanes. It is proposed that an initial HDA followed by a [3,3] sigmatropic rearrangement account for the stereochemistry of the products <96JCS(P1)443>. 

Thia-[2,3]-Wittig sigmatropic rearrangement of lithiated carbanions 47, obtained by deprotonation of the S-allylic sulfides 46, affords the thiols 48 or their alkylated derivatives 49. The corresponding sulfonium ylides 51, prepared by deprotonation of the sulfonium salts 50 also undergoes a [2,3]-sigmatropic shift leading to the same sulfides 49 [36,38] (Scheme 13). As far as stereochemistry is concerned, with crotyl (R R =H,R =Me) and cinnamyl (R, R =H,R =Ph) derivatives, it has been shown that the diastereoselectivity depends on the nature of the R substituent and on the use of a carbanion or an ylide as intermediate. 

This stereoselectivity can be explained by a cyclic transition state for the sigmatropic rearrangement step. The observed stereochemistry results if the alkyl substituent adopts a... 

The [2,3]- or [3,3]-sigmatropic rearrangements (Scheme 24) provide a means to introduce either the protected amine or the carbon atom which will become the carboxylic acid, while also positioning the double bond in the correct position for the alkene isosteres. Moreover, when starting from homochiral allyl alcohols, a very effective chirality transfer assures the stereospecific construction of the R1 and R2 side-chain stereochemistries. 

A variety of sigmatropic rearrangements through six-electron transition states are known. In contrast to the rare [l,3]-migrations, [l,5]-shifts of hydrogen in dienes, suprafacially allowed, occur readily. The experiment outlined in Equation 12.88 confirms the predicted stereochemistry.139 The authors estimated the... 

Sigmatropic rearrangements in anions are more rare, but the isomerization of the conjugated anion 5.42 to the conjugated anion 5.45 probably takes place by a [1,6] shift 5.43 —> 5.44. It is known to be intramolecular, but the stereochemistry (antarafacial is allowed) could not be checked. In order for the reaction to take place at all, it is necessary for the stereochemistry within... 

In this primer, Ian Fleming leads you in a more or less continuous narrative from the simple characteristics of pericyclic reactions to a reasonably full appreciation of their stereochemical idiosyncrasies. He introduces pericyclic reactions and divides them into their four classes in Chapter 1. In Chapter 2 he covers the main features of the most important class, cycloadditions—their scope, reactivity, and stereochemistry. In the heart of the book, in Chapter 3, he explains these features, using molecular orbital theory, but without the mathematics. He also introduces there the two Woodward-Hoffmann rules that will enable you to predict the stereochemical outcome for any pericyclic reaction, one rule for thermal reactions and its opposite for photochemical reactions. The remaining chapters use this theoretical framework to show how the rules work with the other three classes—electrocyclic reactions, sigmatropic rearrangements and group transfer reactions. By the end of the book, you will be able to recognize any pericyclic reaction, and predict with confidence whether it is allowed and with what stereochemistry. 

We have expanded our collection of stereoselective reactions even more in the making of alkenes by the Wittig reaction (chapter 15), from acetylenes (chapter 16), by thermodynamic control in enone synthesis (chapters 18 and 19) and in sigmatropic rearrangements (chapter 35). We have seen that such E- or Z-alkenes can be transformed into three-dimensional stereochemistry by the Diels-Alder reaction (chapter 17), by electrophilic addition (chapters 23 and 30), by carbene insertion (chapter 30) and by cycloadditions to make four-membered rings (chapters 32 and 33). 

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