Dithioester

The extracts were kept below 0°C (note 5). The combined extracts were washed with 5i acetic acid and subsequently dried over magnesium sulfate (note 6). The extract was concentrated in a water-pump vacuum to about 60 ml by means of the rotary evaporator, care being taken that the bath temperature remained below 25°C. The remaining pale yellow solution was warmed to about 35°C (internal temperature). The temperature rose gradually but was kept at about 45°C by occasional cooling. When after about 45 min the exothermic reaction had subsided, the flask was placed in a water-bath at 55°C. After 30 min the remaining pentane was removed in a water--pump vacuum. The orange residue, n 1.5878, yield aa. 92% was almost pure allenic dithioester. 

Note 5. At room temperature the 3,3-sigmatropic rearrangement begins. The anmonia, still present during the work up, will cause ring closure of the allenic dithioester to a 2-ff-thiopyran derivative. 

Mote 1. Distillation at 10-20 mmHg may give rise to 3,3-sigmatropic rearrangement of the product and decomposition of the allenic dithioester formed. 

Analogous open-chain precursors also lead readily to 1,3-dithiolylium salts. S-a-Oxoalkyl thioesters such as (20) on treatment with perchloric acid in glacial acetic acid and HaS undergo ready cyclization to the 1,3-dithiolylium perchlorate (22) (66AH0.7)39). The oxoalkyl dithioesters (21) are probably intermediates in this cyclization as they themselves undergo cyclization with warm 70% perchloric acid or sulfuric acid (80AHC(27)15l). 

As attractive as the transannular bridging of bis(thiolactones) to bicyclic bis(oxepane) frameworks is, our inability to convert the disulfide bridging product (see 25, Scheme 5) to a mmv-fused bre-vetoxin-type bis(oxepane) (see 28) necessitated the development of a modified, stepwise strategy. This new stepwise approach actually comprises two very effective methods for the construction of cyclic ethers the first of these is the intramolecular photo-induced coupling of dithioesters, and the second is the reductive cyclization of hydroxy ketones. We will first address the important features of both cyclization strategies, and then show how the combination of the two can provide an effective solution to the problem posed by trans-fused bis(oxepanes). 

Scheme 8. Oxepane synthesis by photo-induced ring closure of dithioesters. The term dithioester is used in this chapter to describe compounds of type 39 even though such systems are sometimes referred to as dithionoesters or dithioxoesters.

Having developed effective synthetic methodology for the construction of seven-membered cyclic ethers, we were confident that the problem of the frans-fused bis(oxepane) system could now be addressed on a solid foundation. It was our hope that the breve-toxin-type bis(oxepane) system could be assembled by a stepwise strategy utilizing both photochemical dithioester and reductive hydroxy ketone cyclization methods. 

Scheme 11. Bis(oxepane) synthesis using a photochemical dithioester cyclization and a reductive hydroxy ketone cyclization.

In contrast to the usual anti selectivity a remarkably high syn selectivity is observed in the addition of thioester enolates to 2-alkylidenealkanones297. The syn selectivity is probably due to a stereoselective internal autoprotonation of the resulting enolates by the dithioester a-pro-tons298 in these cases where the prostereogenic centers reside exclusively in the enone part (see also Section D.2.I.). 

Living radical polymerization using thiocarbonylthio RAFT agents (including dithioesters, trithiocarbonates and xanthates) was first described in a patent published in 1998.40S The first paper describing the process also appeared in 1998.1R Other patents and papers soon followed. Papers on this method, along with NMP and ATRP, now dominate the literature on radical polymerization. 

O-Alkyl xanthates and A -ary l-A -alkyl dithiocarbamates are effective with vinyl acetate. 97 Dithioesters and trithiocarbonates give severe retardation or even inhibition which is attributed to slow fragmentation of the adduct radical. 

Living Radical Polymerization Table 9.11 Other Aromatic Dithioester RAFT Agents... 

Keywords. Phosphorus and sulfur derivatives, Dithioesters, Hetero Diels-Alder, Sigmatropic rearrangements. Chiral ligands... 

Beside thioamides, dithioesters are the most stable and accessible thiocarbonyl compounds. Their specific reactivity, in particular towards nucleophiUc reagents and their apphcations to the formation of carbon-carbon bonds, have already been reviewed [8]. However, as shown below, the presence of a phosphonate function alpha or beta to the thiocarbonyl group in phosphonodithioformates and phosphonodithioacetates makes these difunctional compounds very versatile building blocks. Moreover, for the phosphonodithioacetates, the substitution of the methylenic hydrogen atoms by fluorine increases again their potential as intermediates for the synthesis of modified natural and bioactive phosphorylated structures. 

In these a-phosphorylated dithioesters, the electron-withdrawing effect of the phosphono group, which strongly increases the electrophilic character of the thiocarbonyl group, makes the latter more prone to the thiophilic attack of nucleophiles and stabilizes the resulting carbanion. The main reactions of 1 with nucleophiles are summarized in Scheme 2. 

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