Xanthate-dithiocarbonate rearrangement

The synthesis of (5 S)-thiolactomycin (792), an enantiomer of an antibacterial agent, makes use of a Wittig olefination early in the sequence as a way of preparing a,jS-unsaturated ester 786 (Scheme 106). The key step in the synthesis is an allyl xanthate-dithiocarbonate rearrangement of 788 to 789. This process occurs upon distillation of 788 at 145 °C (0.4 mm Hg) and gives the desired product 789 in nearly quantitative yield. Chirality transfer is equally efficient, with an enantiomeric excess of at least 98% [222]. 

The thermal rearrangement of allylic xanthates to allylic dithiocarbonates is a well-known reaction which results in the creation of a new stereogenic carbon center when the starting xanthate contains an unsymmetrically substituted C-C double bond. Moreover, in the case of chiral xanthates this rearrangement is accompanied by the transfer of chirality from the stereogenic carbon atom in the substrate to the newly created stcrcogcnic center in the product. 

Fully stereoselective allylic xanthate to allylic dithiocarbonate rearrangement was first observed with diastereomeric 2,3-unsaturated sugar derivatives 1 and 3 which on heating (140 UC for 1 to 2 h) gave the diastereomers of 3,4-unsaturated sugar dithiocarbonates 2 and 4, respectively43. 

A number of catalysts of Pd(II), Pt(II), Rh(I), and Ir(I) induce rearrangements of 0-a11y1ic-.9-methy1 dithiocarbonates at 25°C (45). In a relatively low temperature procedure, olefins readily form from certain classes of xanthate esters (46) ... 

The thermal rearrangement of an allyl xanthate to a dithiocarbonate was used to introduce the sulfur atom on a quaternary carbon in the synthesis of agelasidine A, a natural S-containing sesquiterpene [494]. 

Hu, Sun and Scott described recently an efficient synthesis of some taxadiene derivatives266. In their approach, alcohol (66) is treated with carbon disulphide followed by methyl iodide under standard conditions for the formation of xanthates, to afford the dithiocarbonate (67) in a process that presumably involved a Claisen rearrangement (Scheme 9). Interestingly, 67 undergoes smooth reaction with B SnH to provide the required products (68, 69)266. 

A crucial step in the synthesis of thiotetronic acids involves a fully stereoselective allylic xanthate to dithiocarbonate rearrangement45. Rearrangement of ethyl ( )-(4S)-2-methyl-4-[methylthio-(thiocarbonyl)thio]-2-pentenoate (7) gives ethyl (/f)-(2.S)-2-methyl-2-[methylthio(curbonyl)thio]-3-pentenoate (8) as a single diastereomer with an -configurated double bond and at least 98% ee. This value was determined by Mosher derivatization of the alcohol prepared from the dithiocarbonate in three steps. The remainder of the (5S)-thiotetronic acid synthesis is shown in the scheme. 

However, as shown by Taguchi, xanthates rearrange to the corresponding dithiocarbonates when no /3-hydrogens are present (Scheme 43) [113,114]. 

A free-radical approach has also been successfully applied to the synthesis of primary allylic tributylstannanes (Eq. 8) [10]. The sequence involves a thermal [3,3] rearrangement of an allylic methyl xanthate then addition of a BusSn radical to the double bond of the derived dithiocarbonate intermediate and subsequent loss of COS in a chain-propagating step. 

The utility of the [3,3]-sigmatropic rearrangement of eight-membered thionocarbon-ates for the highly stereo-controlled synthesis of Z- or -double bonds in 10-membered thiolcarbonates has been reviewed.5,5-Disubstituted thiotetronic acids (139) have been synthesized using an allylic xanthate (137) to dithiocarbonate (138) rearrangement which has permitted the introduction of a sulfur at a tertiary centre with concomitant deconjugation of the double bond (see Scheme 39). 

A-Propargyl dithiocarbonates (xanthates) 533 bearing a variety of substituents were convenient precursors of 1,3-dithiole-2-ylidene derivatives 534 by reaction with active methylene compounds involving a [3,3]-sigmatropic rearrangement (Equation 64) <1995TL5171>. In all cases except dibenzoylmethane, a mixture of regioisomers was obtained, with double bond exo or endo. 

Sugar allyltin derivatives are very useful synthetic intermediates. The most convenient and reliable method for their preparation is a so-called xanthate procedure. The first compound of this class was prepared in 1988 by Mortlock and Thomas [74]. 1,2-0-isopropylidene-D-glycer-aldehyde (80) was converted into allylic alcohol and further transformed into the corresponding xanthate 81. This compound underwent thermal [3,3] rearrangement into the dithiocarbon-ate 81a, which upon reaction with tri-n-butyltin hydride provided the final sugar allyltin 82 as a mixture of isomers with the E-one strongly predominating (O Scheme 35). 

In an approach to the total synthesis of milbemycin /) , the attempted xanthate formation of 3 occurred with [3,3] sigmatropic rearrangement yielding dithiocarbonate 4 bearing exclusively the (i -alkene geometry368. 

The heating of xanthates usually results in /3-elimination and formation of olefins (Chugaev reaction ). However, when there is no /3-hydrogen at the alcohol moiety, rearrangement takes place. A kinetic study of the influence of substituents on the reaction rate of a series of diaryl xanthates to diaryl dithiocarbonates (81->82) again indicates a four-membered cyclic transition state . A similar transition state is indicated, by the same... 

Oxathians the formation of cyclic trithio-orthocarbonates (193) by the thermolysis of bis-(dithiocarbonates) the preparation of l,3-oxathiol-2-ones and of 2-substituted 1,3-oxathioles by treatment of moKlibromo-ketones with potassium ethyl xanthate a novel synthesis of 2/f-l,3-benzoxathiol-2-ones (194) by the HI- or pyridine-hydrochloride-induced cyclization of thiocarbamates and the base-catalysed cyclization and Smiles rearrangement of 3-(2,4,6-trinitrophenyl-thio)propanoI to give the benzoxathiepin (195). ... 

The same group of workers also accounted for the thermal rearrangement reaction of di(ethylthio)propyl S-methyl xanthates and the rearrangement of 0,S-dialkyl dithiocarbonates that occurs under Friedel-Crafts reaction conditions. A new, general synthesis of l,3-dithiol-2-ones (451) is based on the acid-catalysed ring-closure reaction of the dithiocarbonates (452). The rearrangements of 2-aminoethyl alkyl trithiocarbonates (453) and alkylthio-thiocarbonyl thiocyanates (433) into dithiocarbonates (454) and alkylthio-thiocarbonyl isothiocyanates (455), respectively, have been described recently. 

---