Sigmatropic rearrangements alcohol synthesis

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. 

Allylic nitro compounds undergo [2.3]sigmatropic rearrangement to afford rearranged alcohols, as shown in Eq. 7.4346 and Eq. 7.44 47 Because the allylic nitro compounds used in these reactions are readily prepared either by the Henry reaction or the Michael addition, these reactions may be useful in organic synthesis. 

There are several variations of the Claisen rearrangement that make it a powerfid tool for the synthesis of y,<5-unsaturated carboxylic acids. The ortho ester modification of the Claisen rearrangement allows carboalkoxymethyl groups to be introduced at the /-position of allylic alcohols.157 A mixed ortho ester is formed as an intermediate and undergoes sequential elimination and sigmatropic rearrangement. 

Treatment of the selenide (19) with unbuffered 30% hydrogen peroxide-THF yields the cis- and trans-linalyl oxides (247) via [2,3] sigmatropic rearrangement. Kossanyi et al. have improved upon the efficiency of Vig s synthesis of the four lilac alcohols (248). The synthesis of the furanoid (249), formed during sulphuric acid-catalysed dimerization of isoprene, is straightforward. The known half-... 

Ortho ester Claisen rearrangement.2 The [3,3]sigmatropic rearrangement of allyl vinyl alcohols prepared from this ester results in a regiospecific synthesis of diethyl allylmalonates. 

A tandem sequence of double [2,3]-sigmatropic rearrangement-six-electron electro-cyclization-4 + 2-cycloaddition has been shown to convert acyclic ene-bis(propargyl alcohols) such as (71), via the corresponding bis-sulfenic ethers such as (72), into anthracene (with an intermolecular final cycloaddition) or phenanthrene or related (with an intramolecular cycloaddition) skeletons. The sequence is illustrated in Scheme 12 for synthesis of a steroid skeleton, estra-l,3,5(10)-trien-17-one (73).81... 

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... 

The use of allylic selenides 166 in oxidation reaction leads to intermediate selenoxides 167, which can undergo [2,3]sigmatropic rearrangements to the corresponding allylic selenenates 168. These componds will lead to allylic alcohols 169 after hydrolysis (Scheme 48). This is also a versatile procedure for the synthesis of optically active allylic alcohols, provided that either an asymmetric oxidation or an optically active selenide is used for the rearrangement. Detailed kinetic and thermodynamic studies of [2,3]sigmatropic rearrangements of allylic selenoxides have also been reported.290-294... 

Still etal have reported a highly stereoselective synthesis of the alcohol ( 4) which has been previously converted into the Cis Cecropia Juvenile Hormone (Scheme 3). The key step in this synthesis involves the recently described [2,3] sigmatropic rearrangement of the dilithio dianion derived from (13). Full details of the previously reported Ci and Cig Cecropia Juvenile Hormone syntheses have been published."... 

The [2,3] sigmatropic rearrangement of sulfenate esters 3, prepared in situ on treatment of 4-morpholinesulfenyl chloride with allylic alcohols, allows easy synthesis of diastereomeric allylic sulfinamides 4 (configurations were not established)104. 

In 1967 the work on allylic sulfenates was extended to the trichloromethyl derivatives (Scheme 43) [99,102]. This activity was prompted by a report of Sosnovsky [103], who claimed the synthesis of the sulfenate 158a from chloride 157 and allylic alcohol 156a (Scheme 43). Braverman showed that 158a was not the product of the reaction. Instead the sulfoxide 159a was obtained, presumably via [2,3]-sigmatropic rearrangement. Positive experimental evi-... 

Scheme 44 General synthesis of allylic alcohols based on a-a]k)4ation of allylic sulfoxides followed hy [2,3]-sigmatropic rearrangement...

A Ciba-Geigy group used the Carroll reaction for the synthesis of hydroxyethylene dipeptide iso-steres. Alcohol (80) was converted with diethyl isopropylmalonate to the mixed malonic ester derivative (81) by Ti(OEt)4 catalysis. Subsequent sigmatropic rearrangement of (81) was also effectively catalyzed by Ti(OEt)4, thereby allowing a one-step conversion of the allylic alcohol (80) to ester (82) (Scheme 13). 

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