Stereospecificity sigmatropic rearrangements

These reactions will be discussed in more detail under the topic of 3,3-sigmatropic rearrangements in Chapter 11. For the present we simply want to focus on the fact that the reaction is stereospecific-, the -isomer gives one diastereomeric product whereas the related Z-isomer gives a different one. The stereochemical relationship between reactants and products can be explained if the reaction occurs through a chairlike transition state in... 

Figure 1. Stereospecific [3,3]-Sigmatropic rearrangement strategy for the construction of ring B. R = Sif-BuMe2.

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. 

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. 

It may be of interest to note that the stereospecific transformation shown in equation 15 has been cited as the first reported observation of an 1 - 3 chirality transfer. It is evident that on rearrangement of optically active 6d to 7d, the chiral center at C-a is eliminated and a new one created at C-y. The term self-immolative asymmetric synthesis has also been used to describe syntheses of this kind. As pointed out by Hoffmann , quantitative 1 - 3 chirality transfer will follow from the suprafacial - course of rearrangement, provided the reactant has a uniform configuration at the j8, y-double bond. This stereochemical prediction has also been confirmed by the results obtained in several other [2,3]sigmatropic rearrangements, subsequently reported " . 

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). 

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 investigators 3 jj... 

When the lactone silyl ketene acetal 18-1 is heated to 135° C a mixture of four stereoisomers is obtained. Although the maj or one is the expected [3,3] -sigmatropic rearrangement product, lesser amounts of other possible C(4a) and C(5) epimers are also formed. When the reaction mixture is heated to 100° C, partial conversion to the same mixture of stereoisomers is observed, but most of the product at this temperature is an acyclic triene ester. Suggest a structure for the triene ester and show how it can be formed. Discuss the significance of the observation of the triene ester for the lack of complete stereospecificity in the rearrangement. 

The reactions of 1,2,3-triazolium 1-imide (277) with a range of alkene and alkyne dipolarophiles give rise to a variety of new ring systems (Scheme 54). Compounds (276) and (278) are obtained from (277) by reaction with acrylonitrile and DMAD, respectively. These reactions are tandem 1,3-dipolar (endo) cycloadditions and sigmatropic rearrangements which are regio- and stereospecific <90JCS(Pl)2537>. Kinetic and mechanistic studies show that these reactions are dipole-HOMO controlled. The second-order rate constants are insensitive to solvent polarity, the reaction indicates... 

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. 

Scheme 24 Concept of Sigmatropic Rearrangement for the Stereospecific Synthesis of ip[CH=CH] Isosteres...

P. L. Armstrong, I. C. Coull, A. T. Hewson, and M. J. Slater, An unusually facile [3,3]sigmatropic rearrangement in a stereospecific synthesis of novel 2, 3 -dideoxynucleo-side precursors, Tetrahedron Lett., 36 (1995) 4311—4314. 

Stereospecificity is a characteristic of sigmatropic rearrangements. For example, the [3,3]-sigmatropic reaction shown in Scheme 8.15 is stereospecific i.e. the stereoisomer of the starting material produces exclusively the stereoisomer of the product shown. 

The selenosulfonates (26) comprise another class of selenenyl pseudohalides. They are stable, crystalline compounds available from the reaction of selenenyl halides with sulftnate salts (Scheme 10) or more conveniently from the oxidation of either sulfonohydrazides (ArS02NHNH2) or sulftnic acids (ArS02H) with benzeneseleninic acid (27) (equations 21 and 22). Selenosulfonates add to alkenes via an electrophilic mechanism catalyzed by boron trifluoride etherate, or via a radical mechanism initiated thermally or photolytically. The two reaction modes produce complementary regioselectivity, but only the electrophilic processes are stereospecific (anti). Similar radical additions to acetylenes and allenes have been reported, with the regio- and stereochemistry as shown in Scheme 11. When these selenosulfonation reactions are used in conjunction with subsequent selenoxide eliminations or [2,3] sigmatropic rearrangements, they provide access to a variety of unsaturated sulfone products. 

The ease of these transformations and the complete stereocontrol was in agreement with the known overall stereospecificity of the selenium(IV) oxide oxidation9,10, and strongly indicated a [2,3] sigmatropic rearrangement of intermediates like 7 leading to selenium(II) esters 8, which finally hydrolyze to the -alcohol 9. 

Similarly, 1-halo-l-sulfonylallenes (139) have been prepared by heating in toluene at 80 °C of propargyl esters (138) via [2,3]sigmatropic rearrangement of the latter (Scheme 32) [51]. 1-Bromo-l-sulfonylallenes 139, when treated with bromine, undergo attack on central allenic carbon with formation of intermediate carbenium bromide followed by hydrogen bromide eUmination, and afford stereospecifically the 2,3-dibromo-l-sulfonyl-l,3-dienes 140. 

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