Unsaturated thioacetals

An unusual reductive elimination can ensue from titanacyclobutanes possessing an alkenyl group at the carbon a to the titanium atom. Thus, alkenylcarbene complexes 48, prepared by the desulfurization of (fy-unsaturated thioacetals 49 or l,3-bis(phe-nylthio)propene derivatives 50 with a titanocene(II) reagent, react with terminal olefins to produce alkenylcyclopropanes 51 (Scheme 14.22, Table 14.4) [37]. This facile reductive... 

The acid-induced cyclization of unsaturated thioacetals (19) gives anti-Markovnikov products (20), apparently involving sulfur elimination and readdition.37... 

Titanocene(n) species promote the conversion of unsaturated thioacetals to cyclic compounds. This cyclization proceeds with the loss of the terminal alkene carbon. Treatment of the thioacetal 83 with the low-valent titanium species Cp2Ti[P(OEt)3]2 (3 equiv) in refluxing THF afforded benzoxocines 86 and 87 (by isomerization of 86) in 61% yield (Scheme 14) <1999SL354>. Using 4 equiv of the titanocene(n), the yield is higher (70%) but the selectivity is lower (the ratio 86 87 becomes 82 18). The mechanism or the reaction probably involves the formation of the titanium carbene complex 84, its intramolecular reaction with the double bond to form titanocyclobutane 85, and the subsequent elimination of methylidenetitanocene <1999SL354>. 

Scheme 9. Titanocene(II)-promoted ring-closing metathesis of unsaturated thioacetals.

This RCM has proven to be a useful synthetic method for the construction of a variety of heterocycles. Mono and bicyclic unsaturated ethers and sulfides are obtained from alkenyl thioacetals having an ether or sulfide linkage (Table 14.2) [30],... 

Nitrogen heterocycles can also be prepared by the RCM of unsaturated amines having a diphenyl thioacetal moiety (Table 14.3) [31]. 

Crossed Michael-type reactions of thioacetates MeCOSCH(R )CH,CHO with a,(3-unsaturated... 

The conjugate additions of thiols to a,p-unsaturated electrophiles was extended by Wang [96]. Catalyst 166 promoted the addition of thioacetic acid to a variety of enones, including aliphatic, aromatic and heteroaromatic substituents (Scheme 42). Wang expanded the scope of the reaction to include asymmetric additions of thioacetic acid to nitro-olefms (Scheme 43) [97]. Thiourea catalyst 166 promoted the addition reactions in high yields and high enantiomeric ratios for a variety of P-substituted nitro-olefms. 

The reactions proceeded efficiently under mild conditions in short time. The silyl enol ethers reacted with the activated acetals or aldehydes at -78 °C to give predominant erythro- or threo-products [136, 137] respectively. In the same manner, the aldol reaction of thioacetals, catalyzed by an equimolar amount of catalyst, resulted in <-ketosulfides [139] with high diastereoselectivity. In the course of this investigation, the interaction of silyl enol ethers with a,]3-unsaturated ketones, promoted by the trityl perchlorate, was shown to proceed regioselec-tively through 1,2- [141] or 1,4-addition [138]. The application of the trityl salt as a Lewis acid catalyst was spread to the synthesis of ]3-aminoesters [142] from the ketene silyl acetals and imines resulting in high stereoselective outcome. 

The reaction of ot,p-unsaturated acetals predominantly affords regioisomer 19 with the acetal group attached to the C(4) position of the isoxazoline (127). With the analogous thioacetal, the regioselectivity was reversed (117) (Table 6.5). 

TABLE 6.5. RATIOS OF 4- AND 5-REGIOISOMERS 19 AND 20 IN CYCLOADDITIONS TO a,P-UNSATURATED ACETALS AND THIOACETALS"... 

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],... 

Another simple elimination reaction on the thiosulfinate ester makes another molecule of the sulfenic acid and a highly unstable unsaturated thioaldehyde, which promptly dimerizes to give a thioacetal found in garlic as a potent platelet aggregation inhibitor. 

Oxyselenation ofalkeues, - Treatment of olefins with 1 or 2, water, and an acid catalyst (e.g., p-TsOH) in CH2CI2 affords j3-hydroxy selenides in excellent yield. Unsaturated carboxylic acids, phenols, alcohols, thioacetates, and urethanes react with 1 or 2 and an acid catalyst ( —78- 25°) to afford products of oxidative cyclization. These reagents are superior to benzeneselenenyl halides for selenium-induced ring closures. This reaction is also useful for synthesis of 14- and 16-membered lactones. Benzeneselenenyl halides and benzeneselenenic acid do not promote macrolide formation under similar conditions. 

Asymmetric induction also takes place in the cinchona catalyzed addition of thioacetic acid to a,/3-unsaturated dicarboxylic acid esters. Both the reaction rate and optical purity of the addition products are influenced by the nature of the alkoxy or thioalkoxy group in the unsaturated substrate. Generally, thioesters are more reactive towards thioacetic acid and better enantioselectivities are observed for unhindered esters11. 

Vinylketene thioacetals react by a Michael-type addition with an alkyllithium in THF at -80 to —20°. Thus successive addition of n-butyllilhium and methyl iodide to (8) gives the thioacetal of thea,/i-unsaturated methyl ketone (9) in almost quantitative... 

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