Cyclic thioacetals

Some cyclic thioacetals have an A-SE2 hydrolysis mechanism,206 as do some 2-aryl-2-methyl-l,3-dithianes, except for the 4-NO2 derivative, which looks more A2-like.207 In 10 vol% dioxane/aqueous HC104 mixtures, reactive 2-aryl-2-phenyl-l,3-dithianes are believed to have an A-SE2 hydrolysis mechanism, whereas the least reactive ones have an A2 mechanism.130 Isothiocyanates are believed to hydrolyze by a mechanism that involves simultaneous proton transfer to nitrogen and attack of water at carbon in a cyclic transition... 

An efficient asymmetric synthesis of the five-membered cyclic thioacetate 19da from acetate rac-ldb or carbonate rac-lda was precluded because of the operation of a strong memory effect and other effects. Therefore the Pd-catalyzed reaction of the naphthoate rac-ldc with KSAc in the presence of Pd(0)/L (2 mol%) and BPA (8 mol%) in CH2CI2/H2O was investigated. Indeed, reaction of the naphthoate rac-ldc gave thioacetate 19da with 92% ee in high yield. 

The compound in which the 3-keto group is reduced to a hydrocarbon interestingly still acts as an orally active progestin. The preparation of this compound starts with the hydrolysis of dihydrobenzene (13-2) to afford 19-nortestosterone (15-1). Reaction with ethane-1,2-thiol in the presence of catalytic acid leads to the cyclic thioacetal (15-2). Treatment of this intermediate with Raney nickel in the presence of alcohol leads to the reduced desulfurized derivative (15-3). The alcohol at 17 is then oxidized by any of several methods, such as chromic acid in acetone (Jones reagent), and the resulting ketone (15-4) treated with hthium acetylide. There is thus obtained the progestin lynestrol (15-5) [18]. 

Some non-cyclic thioacetals have been used sometimes, particularly those bearing phenylthio groups or some special feature such as an extra electron-withdrawing group. The corresponding carbanion can then be used for a 1,4 addition on an a,(J-unsaturated ketone as reported [282],... 

In general, thioacetals can be made in a similar way to normal (oxygen-based) acetals-by treatment of an aldehyde or a ketone with a thiol and an acid catalyst—though a Lewis acid such as BF3 is usually needed rather than a pro tic acid. The most easily made, most stable toward hydrolysis, and most reactive towards alkylation are cyclic thioacetals derived from 1,3-propanedithiol, known as dithianes. 

Several cyclic thioacetals 266-268, closely related to 1,3-dithiane, have been described as formyl anion equivalents. 1,3,5-Trithiane (266)442,443, as well as 4,5-dihydro-5-methyl-... 

Open chain and cyclic thioacetals 1,3-Dithiolane and 1,3-dithiane derivatives are versatile intermediates in the synthesis and interconversion of monocarbonyl and 1,2-dicarbonyl compounds. Protection of carbonyl groups as their open-chain and cyclic thioacetals is an important method in the synthesis of organic molecules. Thioacetals are stable... 

Cyclic thioacetals in C-C bond forming reactions with participation of S-electrophiles 88MI15 90MI11. 

Radical reactions of cyclic thioacetals 88MI127 90MI7. 

Some of the problems associated with the synthesis of a-dicarbonyl starting materials have been alleviated by the use of propane-1,3-dithiol, which reacts with aldehydes to give cyclic thioacetals. With butyllithium the resulting stable dithiane anions (134) can be transformed into a-diketones or a-hydroxy ketones (Scheme 73). A further approach to such compounds is found in the reaction of a-ketonitrate esters with sodium acetate (Scheme 73), while aryl a-diketones are also available from a-ketoanils (prepared from the cyanide-ion-catalyzed transformation of aromatic aldimines) (70AHC(12)103). 

Although 1,2-dicarbonyl substrates (especially unsymmetrical benzils) are often difficult to make, there are a number of approaches which may be appropriate. Propane-1,3-dithiol reacts with aldehydes to give cyclic thioacetals (in 52-91% yields) which form stable dithiane anions when treated with butyllithium. Subsequent quenching with an acid chloride followed by mercury(ll) chloride treatment gives a 1,2-dicarbonyl species. Alternatively, substitution of an aldehyde for the acid chloride gives rise eventually to an a-hydroxycarbonyl derivative (Scheme 5.1.2) [16j. An alternative approach to a-ketoaldehydes (82-86% yields) reacts an a-ketonitrate ester with sodium acetate in DMSO [17]. Aryl a-diketones can be made from a-ketoanils, which are in turn made by cyanide ion-catalysed transformation of aromatic aldimines [18], and the range of unsymmetrical benzils has been increased by... 

Ethylene and thioformaldehyde are the products of irradiation of matrix-isolated thietane at lOK. Sulphur-carbon bond homolysis has also been observed on irradiation of the nucleoside membrane transport inhibitor, 6-[ (4-nitrobenzyl) thio] -9- (/8-D-ribofuranosyl) -purine (94), and the oxazolidin-2-one (95) has been converted into the allyl derivative (96) by photochemically induced radical allylation.Efficient conversion of cyclic thioacetals into the corresponding carbonyl compounds under neutral conditions has been achieved by 2,4,6-triphenylpyrylium tetrafluoroborate-sensitised irradiation in moist dichloromethane,and diaryl sulphides and the corresponding sulphoxides and sulphones have been reported to undergo anion-promoted carbon-sulphur bond photocleavageboth processes appear to involve an initial electron transfer. Sulphur-hydrogen bond horaolysis has been reported in t-butanethiol and is also responsible for the photoinitiated thiylation of fluorobromoethylenes and of trialkylethynylsilanes and t-butylacetylene. 

Reaction of dichloroketene with cyclic thioacetals 11 of a,/ -cycloalkenones yields 1,7-dithiacy-cloalk-5-en-2-one derivatives 12 (Table 4) by a four-carbon cycloenlargement341. 

Table 4. Reactions of Dichloroketene with Cyclic Thioacetals of a,/LCvcloalkenones341...

A solution of cyclic thioacetal 11 (0.027 mmol) and dichloroacetyl chloride (0.03 mmol) m 60 mL ofhexane is stirred at r.t. under N, and a solution of Et,N (0.033 mol) in 20 mL ofhexane is slowly added over 1 h. After 3-4 h at r.t. 250 mL of CH2C12 and 100 mL of H20 are added, and the brown organic layer is washed with three 30-mL portions of 5 % HC1, two 30-mL portions of H,0, three 50-mL portions of 5 % aq Na,C03, and two 30-mL portions of sat. aq NaCl. The organic layer is dried over Na2S04 and evaporated under reduced pressure. The reaction mixture is purified by crystallization from hexane and decolorized with charcoal. White crystals arc collected by filtration and dried (see Table 4). 

Cyclic Acetals Formation of an acetal using a diol as the alcohol gives a cyclic acetal Cyclic acetals often have more favorable equilibrium constants, since there is a smaller entropy loss when two molecules (a ketone and a diol) condense than when three molecules (a ketone and two molecules of an alcohol) condense. Ethylene glycol is often used to make cyclic acetals its acetals are called ethylene acetals (or ethylene ketals). Dithiane (Section 18-8) and its alkylated derivatives are examples of cyclic thioacetals (sulfur acetals). 

The by-products in the syntheses using 5-thio-D-gaIactose previously reported (see Vol. 13, p. 102) have been investigated. In the methanolysis of the ethyl furanoside (13) with methanol-hydrogen chloride, the thio-derivatives (14), (15), and the sulphur-ring derivative (16) were identified. The 1,5-thiane derivative (14) was also a by-product in the acetolysis of (13). A by-product in the hydro-brominolysis of methyl 2,3,4,6-tetra-0-acetyl-5-thio-a-D-galactopyranoside was found to be the cyclic thioacetal (17). Mechanisms for the formation of (13)-(17) are suggested. ... 

The mechanism of this transformation is directly analogous to acetal formation, with sulfur atoms taking the place of oxygen atoms. If a compound with two SH groups is used, a cyclic thioacetal is formed ... 

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