Desulphonylation alkylative

Solanesol and other prenyl alcohols are important as metabolites in mulberry and tobacco leaves and in the synthesis of isoprenoid quinones. Hence, Sato and collaborators107 have developed a stereoselective synthesis of all-trans-polyprenol alcohols up to C50. Construction of the requisite skeletons was accomplished by the alkylation of a p-toluenesulphonyl-stabilized carbanion, followed by reductive desulphonylation of the resulting allylic sulphonyl group. This was achieved most efficiently by the use of a large excess of lithium metal in ethylamine (equation (43)), although all reaction conditions led to mixtures. The minor product results from double bond rearrangement. 

Trost published a desulphonylation procedure for aryl alkyl sulphones using an excess of sodium amalgam in buffered ethanol126 (equation 52). Trost claimed that this is superior to earlier reactions using sodium amalgam in ethanol because of a couple of factors the use of the acid phosphate buffer to prevent formation of significant amounts of sodium methoxide is particularly important, since this can cause isomerizations in base-sensitive substrates, and the temperature should be kept low, but optimized for each substrate. 

Eisch, Behrooz and Galle196 give compelling evidence for the intervention of radical species in the desulphonylation of certain acetylenic or aryl sulphones with metal alkyls having a lower oxidation potential at the anionic carbon. The primary evidence presented by these workers is that the reaction of 5-hexenylmagnesium chloride outlined in equation (85) gives a mixture of desulphonylation products, in accord with the known behaviour of the 5-hexenyl radical, in which the cyclopentylmethyl radical is also formed. 

Finally, an ingenious synthetic sequence by Trost, Cossy and Burks201 includes a unique desulphonylation reaction that involves an electron-transfer process. The synthetic sequence uses 1, l-bis(phenylsulphonyl)cyclopropane as a source of three carbon atoms, since this species is readily alkylated even by weakly nucleophilic species. Given an appropriate structure for the nucleophile, Trost found that desulphonylation with lithium phenanthrenide in an aprotic solvent allowed for an efficient intramolecular trapping of the resultant carbanion (equation 88). This desulphonylation process occurs under very mild conditions and in high yields it will undoubtedly attract further interest. 

In all the desulphonylation reactions discussed in Sections III.B and III.C the sulphur is lost from the starting sulphone and is reduced in the process simultaneously, the former carbon-sulphur bond is either reduced to a C—H bond or is converted into a C=C bond. The reactions described in this section have the common thread that the sulphur atom is lost with reduction at sulphur, but the carbon atom is converted directly into a carbonyl group. Formally, these reactions offer a route from alkyl halides to aldehydes or ketones. 

Pioneering work on the desulphonylation of jS-ketosulphones was carried out by Corey and Chaykovsky - . This reaction was part of a sequence which could be used in the synthesis of ketones, as shown in equation (53). The main thrust of this work was in the use of sulphoxides, but Corey did stress the merits of both sulphones and sulphonamides for different applications of this type of reaction. The method soon found application by Stetter and Hesse for the synthesis of 3-methyl-2,4-dioxa-adamantane , and by House and Larson in an ingenious synthesis of intermediates directed towards the gibberellin skeleton, and also for more standard applications . Other applications of the method have also been madealthough it does suffer from certain limitations in that further alkylation of an a-alkyl- -ketosulphone is a very sluggish, inefficient process. Kurth and O Brien have proposed an alternative, one-pot sequence of reactions (equation 54), carried out at — 78 to — 50°, with yields better than 50%. The major difference between the two routes is that the one-pot process uses the desulphonylation step to generate the enolate anion, whereas in the Corey-House procedure, the desulphonylation with aluminium amalgam is a separate, non-productive step. 

Anions from the Schiffs base (78) can be C- or A -alkylated with ethyl iodide or diethyl sulphate. The ratio of the products depends both on the solvent and on the presence of 18-crown-6. In non-polar solvents, the crown ether increases the solubility of the base, and C-alkylation is the major pathway. In dipolar aprotic solvents, the 18-crown-6 breaks up ion pairs by solvation of the Na" cation, and favours A -alkylation. A nerylsulphonamide, formed from (79), undergoes regiospecific reductive desulphonylation to give nerol (80), which implies that (79) is an effective synthon for cisoid iso-prenoids. Chiral complexes of crown ethers, e.g. (81), catalyse the Michael addition reaction of j3-keto-esters and methyl vinyl ketone to give adducts in high optical yields. ... 

These authors31 also reported that the desulphonylation reaction of the mixture of 19 and 32 was endothermic by 3.6kcalmol-1 and resulted in a mixture of primary and secondary chlorododecanes (33 and 34) they could also form by direct chlorination of the hydrocarbon. The heat of formation of 1-chlorododecane (33) is well established as —93.8 + 0.6 kcal mol l. Let us assume that the difference between heats of formation of isomeric primary and secondary chlorides is a constant, and so <5A/Jf(lq, 33, 34) = <5AHf(lq, n-PrCl, i-PrCl) = 2.7 + 0.5 kcal mol-1. [Interestingly, there are no reliable data for any isomeric pair of alkyl chlorides save these propyl chlorides—for 1- and 2-chlorobutane 35a and 35b, <5AHf(lq, 35a, 35b) = 1.1 + 2.0 kcal mol - The heats of formation of any of the various liquid secondary chlorododecanes lumped together here as 34 are all ca... 

Dihydrothiophen 1,1-dioxides (3-sulpholenes) have been demonstrated to be very versatile masked diene synthones in organic synthesis. Thus, alkylation with different alkyl halides can be used to mono-alkylate to (210) and dialkylate to a mixture of (211) and (212). Desulphonylation can be achieved in various ways. Treatment of (211) with LiAlH in ether gave exclusively (213) in 90% yield, while treatment of (212) with potassium hydroxide or potassium carbonate in ethanol at 125°C gave exclusively (214) in... 

Bromination, dehydrobromination, and direct alkylative desulphonylation of sulphone (140) gave a mixture of 1,2,3,4- and 1,2,3,8-tetramethylcycIo-octatetraenes, with the 1,2,3,4-isomer predominating (70—80%). Treatment of this mixture with iV-phenyltriazolinedione gave a mixture of Diels-Alder adducts (141 = H, =... 

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