Sigmatropic reactions rearrangements reversibility

The process shown in Equation 12.112, in the forward direction termed the ene reaction and in the reverse the retro-ene reaction, bears the same relationship to the [3,3]-sigmatropic reactions as does the [2,3]-elimination (p. 668) to the [2,3]-sigmatropic shift. It is also closely related to the [l,5]-rearrangement of hydrogen. The reaction can occur either intermolecularly, as in, for example, Equations 12.113 and 12.114, or intramolecularly, as in Equations 12.115 and 12.116. 

All-carbon ene reactions can go in reverse when ring-strain is released 6.24. This reaction is curious, because it could also be considered as a homologue of a [1,53-sigmatropic rearrangement—it is quite common to think of the chemistry of cyclopropanes as similar to that of alkenes. With heteroatoms in the chain it is possible to drive such reactions in reverse without having to release strain. Thus esters such as acetates and benzoates undergo a cyclic (3-elimination on pyrolysis. This type of elimination is known to be syn... 

Keywords Orbital overlap factor Fragmentation [1,5] sigmatropic shift Epimerization Reverse ene reaction Cope rearrangement EIZ-isomerization... 

This reaction proceeds by a concerted, [3,3] sigmatropic rearrangement (cf. the Claisen rearrangement) where one carbon-carbon single bond breaks, while the new one is formed. It is a reversible reaction the thermodynamically more stable isomer is formed preferentially ... 

Since its discovery two decades ago, the reversible interconversion of allylic sulfenates to sulfoxides has become one of the best known [2,3]-sigmatropic rearrangements. Certainly this is not only because of the considerable mechanistic and stereochemical interest involved, but also because of its remarkable synthetic utility as a key reaction in the stereospecific total synthesis of a variety of natural products such as steroids, prostaglandins, leukotrienes, etc. 

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. 

As a continuation to the studies by Darwish and Braverman on the [2,3]-sigmatropic rearrangement of allylic sulfinates to sulfones, and in view of its remarkable facility and stereospecificity (see Chapter 13), Braverman and Stabinsky investigated the predictable analogous rearrangement of allylic sulfenates to sulfoxides, namely the reverse rearrangement of that attempted by Cope and coworkers . These authors initiated their studies by the preparation of the claimed allyl trichloromethanesulfenate using the method of Sosnovsky . This method involves the reaction between trichloro-methanesulfenyl chloride and allyl alcohol in ether at 0 °C, in the presence of pyridine (equation 6). 

One of the most interesting reactions in sulfur chemistry is the reversible [2,3]sigmatropic rearrangement of allyl sulfoxides to the corresponding sulfenate esters, which are achiral at sulfur. However, in the case of suitably substituted allyl sulfoxides a new chiral center may be generated at the a-carbon in this process, as shown in eq. [137]. 

The mechanism involves 2-oxonia-Cope rearrangements via (Z)-oxocarbenium ion intermediates, as shown in Scheme 7. It has been shown that racemization can be suppressed by conditions or structural features which slow the Cope rearrangement in either forward or reverse directions, since the [3,3]-sigmatropic rearrangement must occur many times before reaction via the less favoured (Z)-oxocarbenium ion becomes important.20... 

The intramolecular nitrone-alkene cycloaddition reaction of monocyclic 2-azetidinone-tethered alkenyl(alkynyl) aldehydes 211, 214, and 216 with Ar-aIkylhydroxylamincs has been developed as an efficient route to prepare carbacepham derivatives 212, 215, and 217, respectively (Scheme 40). Bridged cycloadducts 212 were further transformed into l-amino-3-hydroxy carbacephams 213 by treatment with Zn in aqueous acetic acid at 75 °C. The aziridine carbaldehyde 217 may arise from thermal sigmatropic rearrangement. However, formation of compound 215 should be explained as the result of a formal reverse-Cope elimination reaction of the intermediate ct-hydroxy-hydroxylamine C1999TL5391, 2000TL1647, 2005EJ01680>. 

The Evans rearrangement can be driven to completion by the addition of a thiophile, such as trimethylphosphite (Scheme 26.19) 440 46 M This strategy allows the chemistry of the allyl phenyl sulfoxide, or other sulfur precursor, to be exploited before the allyl alcohol is unmasked.4 3 471 474 The addition of phenylsulfenyl chloride to an alkene, followed by the elimination of hydrogen chloride and subsequent rearrangement, provides a useful synthesis of allyl alcohols.473 475 The [2,3]-Evans sigmatropic rearrangement is concerted and allows for stereochemical transfer.476 477 The reverse reaction, formation of the allyl sulfoxide, results from the treatment of an allyl alcohol using a base followed by arylsulfenyl chloride to produce the allyl sulfoxide.478 479... 

Klunder nicely exploited the Sommelet-Hauser reaction to synthesize dipyridodiazepine derivatives, such as 84, whose structural analogues show potent inhibition of HIV-1 reverse transcriptase.42 The key step here involves a [2,3]-sigmatropic rearrangement across the pyridine ring. 

After your experience with cycloadditions and sigmatropic rearrangements, you will not be surprised to learn that, in photochemical electrocyclic reactions, the rules regarding conrotatory and disrotatory cyclizations are reversed. 

---