Thioacetals, rearrangement

Cyclopropanone thioacetals are useful synthetic intermediates which are made from di-bromocarbene cycloadducts by successive replacement of the bromine atoms with methylsul-fanyl groups. Bicyclo[n.l.O]alkanone thioacetals rearrange in the ring-enlargement mode on treatment with formic acid or trifluoroacetic acid. Cyclononanone and cyclotridecanone have been made by this method-... 

At low temperature a 1 1 adduct of thioacetic acid and an enamine could be prepared (709). The previously described reaction of aminomethylene ketones with hydrogen peroxide was extended to bisaminomethylene compounds. However, acylated cyclohexenamines led to cyclopentane-carboxamides (770), Trichloromethyl adducts of enamines and the rearranged amine derivatives were described in a further study (777). 

The reaction of crotonaldehyde and methyl vinyl ketone with thiophenol in the presence of anhydrous hydrogen chloride effects conjugate addition of thiophenol as well as acetal formation. The resulting j3-phenylthio thioacetals are converted to 1-phenylthio-and 2-phenylthio-1,3-butadiene, respectively, upon reaction with 2 equivalents of copper(I) trifluoromethanesulfonate (Table I). The copper(I)-induced heterolysis of carbon-sulfur bonds has also been used to effect pinacol-type rearrangements of bis(phenyl-thio)methyl carbinols. Thus the addition of bis(phenyl-thio)methyllithium to ketones and aldehydes followed by copper(I)-induced rearrangement results in a one-carbon ring expansion or chain-insertion transformation which gives a-phenylthio ketones. Monothioketals of 1,4-diketones are cyclized to 2,5-disubstituted furans by the action of copper(I) trifluoromethanesulfonate. ... 

Because 2-trimethylsilyloxy sulfides such as 1154 and 1157 are hemiphenyl thioacetals of aldehydes, they are readily hydrolyzed to aldehydes [8-12] or ketones [13]. Thus alkylation of the lithium salt 1162 with cyclohexyhnethylbromide 1163, gives in nearly quantitative yield, the sulfide 1164, which, after oxidation with m-chloroperbenzoic acid and hydrolysis, rearranges in 70% yield to cyclohexylacetal-dehyde 1165 [8] (Scheme 8.2). A more detailed discussion of the formation of aldehydes is given in Section 8.5. 

Cyclization of benzophenones having an o -thioacetic acid, ester or amide group has been used in structure studies and to synthesize 3-phenylbenzo[6 ]thiophenes with specific substituents. Thus (57) was readily converted to (58 X = OH, OEt or NH2) as precursors to a variety of benzo[6 ]thiophenes (57AC(R)705>, and as precursor to the unequivocal synthesis of 3-phenylbenzo[6 jthiophene, to demonstrate a remarkable sulfur-catalyzed rearrangement (59AJC218). 

These methods were extended to 0-hydroxy orthothioesters and p-hydroxy thioacetals [438], leading to ketenethioacetals and vinyl sulfides. With secondary alcohols (R2 - H) a side reaction, which can become preponderant when SOCl2 is used instead of P2I4 in the elimination step, was observed a rearranged product (R2 = SMe in the olefin) was formed. 

Vinyi sulfides, ketene thiocetals.1 These products, as well as the seleno anologs, are readily prepared from /1-hydroxy orthothioesters or /6-hydroxy thioacetals by reaction with P2I4 or PI3 and N(C2H5)3 in CH2C12. Rearrangement products are encountered as by-products when the hydroxyl group is secondary and become the primary products when SOC1, is used. 

Displacement reactions of 3-chloro-l,2-benzisothiazole (26) have already been mentioned in Section II,A, 8.18,19 22 24 In some cases this displacement is accompanied by a rearrangement. Boshagen has shown that treatment of the above-mentioned compound (26) with thioacetic acid yields an A-acyl-3H-l,2-benzodithiole (39).31 This rearrangement is analogous to that described in Section II, C, 2 above. 

A further example of the same type of rearrangement is afforded by the l 2-benzisothiazoline-3-thiones. If the benzisothiazolium salt (40) is treated with thioacetic acid, the product is the 3-arylimino-3/f-1,2-benzodithiole (41), provided R is an aryl group when R is alkyl, the product is the benzisothiazoline-3-thione (42).32 Structures of types 41 and 42 are, however, in equilibrium with each other at 150°, presumably via a dipolar intermediate [Eq. (3)].32 A diradical... 

Treatment of the 2-pyrrolyl allyl thioether (498) with acetic anhydride and quinoline at 170 °C (or in A jV-dimethylaniline at ca. 100 °C) results in a thio-Claisen rearrangement to give the 5-(3-allyl-2-pyrrolyl) thioacetate (499), whilst peracid oxidation of (498) produces the non-rearranged sulfone in low yield and Raney nickel reduction of (498) yields 3-propylpyrrole (78CJC221). The polyphosphoric acid-catalyzed cyclization of (2-pyrrolylthio) acetic acid (501 R = R = H) somewhat unexpectedly yields (502) via the Spiro intermediate, instead of forming the expected oxothiolane (500), which can be obtained by a Dieckmann cyclization of ethyl (3-ethoxycarbonyl-2-pyrrolylthio) acetate (501 R = Et, R = C02Et) (B-77MI30506). 

This slowed down the rate of the [3,3]-sigmatropic rearrangement and likely allowed time for thioacetal to ring-open and form the oxonium ion 808. Subsequent reaction of the Zn enolate with 808 furnished 805 (Scheme 161) <2002CC2534>. 

In their synthesis of fukinone, Marshall and Cohen converted the known ene-ol (340) into (341) by acetylation, allylic oxidation, and conjugate methylation with dimethylcopperlithium. A Wolff-Kishner reduction of (341) followed by oxidation of the resultant alcohol and enol-acetylation yielded (342). The epoxide of (342) was thermolysed to give (343) which, on reaction with iso-propenyl-lithium and selective oxidation, gave the ketol (344) which was converted in two steps into fukinone (335). A number of sesquiterpenoids, e.g. fukinanolide (345), with the rearranged eremophilane skeleton viz. fukinane (346 R = Me) are known. Nay a and Kobayashi have now prepared this parent hydrocarbon by Raney nickel reduction of the thioacetal of fukinan-8-al (346 R = CHO). 

Compounds 116 originated from a 2,3-sigmatropic rearrangement of the oxygen ylide 118, while compounds 117 are formed by a 1,2-insertion reaction. No cyclopropanation took place with analogous thioacetals. The carboxylate counter-ion in the rhodium(II)... 

Brnalt, J., Kvarnstroem, I., Classon, B., Samuelsson, B. Synthesis of [4,5-Bis(hydroxymethyl)-1,3-oxathiolan-2-yl]nucleosides as Potential Inhibitors of HIV via Stereospecific Base-induced Rearrangement of a 2,3-Epoxy Thioacetate. J. Org. Chem. 1996, 61, 3604-3610. 

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