Cleavage of thioketals

Cleavage of thioketals.5 Protection of ketones and aldehydes by conversion to thioketals is rarely used because thioketals are resistant to both acid- and base-catalyzed hydrolysis. Use of mercuric salts has been the most useful procedure known (1, 654 2, 182 3, 136). Japanese chemists now report that cleavage can be effected readily through alkylation with triethyloxonium fluoroborate. Thus alkylation of cyclohexanone ethylenethioketal (1) with the reagent affords the salt (2). Alkaline hydrolysis of (2) gives cyclohexanone in only 36% yield. However, if the salt (2) is shaken with 3 % CuS04 solution in methylene chloride, cyclohexanone is obtained in 81 % yield. 

The following reagents may also be used for the cleavage of thioketals ... 

For (n = 2, 3) T1(N03)3, CH3OH, 25°, 5 min, 73-99% yield.These conditions have been used to effect selective cleavage of a, 3-unsaturated thioketals. ... 

Cyelobutanone has been prepared by (1) reaction of diazomethane with ketene,4 (2) treatment of methylenecyclobutane with performic acid, followed by cleavage of the resulting glycol with lead tetraacetate,s (3) ozonolysis of methylenecyclobutane, (4) epoxidation of methylene-cyclopropane followed by acid-catalyzed ring expansion,7 and (5) oxidative cleavage of cyclobutane trimethylene thioketal, which in turn is prepared from 2-(co-chloropropyl)-l,3-dithiane.8... 

Oxidative cleavage of ethylene tUoketals. Steroidal ketones can be regenerated from ethylene thioketals by oxidation with I1I04. The reaction is rapid, and yields are almost quantitative. 

The cleavage of the sulfur-carbon bond of thioacetals and thioketals,671 thioortho-formates672 [Eq. (3.101)], and tetraalkyl thioorthocarbonates673 [Eq. (3.102)] leads to the corresponding mono-, di-, and trithiocarbenium ions, respectively. Trimethylthio-carbenium ion 361 was also prepared by methylating dimethyl trithiocarbonate [Eq. (3.102)]. 

Completion of the monomeric unit was achieved via Swem oxidation and Arbuzov reaction with trimethylphosphite to give the phosphonate 75 in 31% overall yield from the resolved amino alcohol. Dimeric olefination was effected upon deprotonation to yield the macrocycle 76, which could be converted in 81% yield to optically active vermiculine (56) via sequential cleavage of the thioketal and ketal protecting groups. 

The C18-C28 segment 502 was synthesized starting from epoxide 497 as shown in Scheme 71. The thioketal 500 was synthesized by coupling of 498 and 499, which were derived from epoxide 497. The thioketal 500 was converted into hemiketal 501 via adjustment of the silyl protective group, deprotection of thioketal, oxidative cleavage of the double bond, and acetylene formation. Hydrostannylation/iodination of acetylene 501 gave vinyliodide, and protective group manipulation afforded 502. 

Thioacetals and ketals are important protecting groups used in organic manipulations. The regeneration of carbonyl compounds by cleavage of acid and base-stable thioacetals and thioketals is a challenging task. Cleavage of thioacetals normally requires use of toxic heavy metals such as Ti +, Hg, Ag, Tl +, or uncom-... 

Cleavage of ketals. Dimethyl and diethyl ketals are converted into ketones in 85-95% yield by treatment with iodotrimethylsilane in chloroform saturated with propene, added to eliminate traces of HI in the reagent. Ethylene ketals also react, but give a complex mixture of products. Thioketals are completely stable. The probable mechanism is shown in equation (I). 

The cleavage of thioacetals and thioketals which are stable in acid and base is quite a challenging problem and invariably requires the use of toxic heavy metals such... 

In order to achieve better selectivity in a future oxidative cleavage of ring A, e. g. by ozone after transformation to a quinone system (5), 7-0-methyleucomol (11) has been transformed to its 8-hydroxy derivative (74) by potassium peroxodisulfate and potassium hydroxide in pyridine (47). Treatment of (74) with benzyl bromide and potassium carbonate in aceton gave the dibenzyl product (76) which on thioketalization yielded... 

The substrate 4 required for cyclization was obtained from the Di e I s-A I der adduct 5 (der i vab le from J and 2.) in five steps involving i ) reduction ii) formylation iii) thioketal — ketal exchange iv) osmylation and v) cleavage of vic-alvcol. 

Secondary thiols.8 A new preparation involves dithiolane cleavage with n-butyllilhium to thiones, which are known to be reduced by the same reagent to sec-thiols by /8-hydride transfer. Yields are 78 90% from saturated thioketals. The mtthod is less useful for preparation of aryl substrates owing to competitive ItlflUltttion of the aromatic ring. 

A cyclopropanone thioacetal has also been observed to undergo Ci—C2 cleavage under the normal conditions for thioacetal solvolyses.110> Thus, the esters 135 a and 135 b are formed when the 1,3-dithiopropane ketal of 7,7-norcarane is reacted with mercuric chloride. In this case, HgCl+ acts as an electrophile and attacks the three-membered ring. However, under similar conditions, the cyclopropanone methyl thioketal 136 forms the mixed ketal 137. While the authors consider this result to represent an unusual example of a nucleophilic displacement at a cyclopropyl carbon atom 110), the reaction mechanism may involve the inter-... 

Mercaptans are generally prepared by displacement reactions. However. secondary or hindered mercaptans are more difficult to obtain. The dithiolane cleavage icaction is a convenient in situ generation of thioketones which are known to be reduced with butyllithium to secondary mercaptans by p-hydrogen transfer Table I shows a number of mercaptans prepared from saturated thioketals in 78-90% yields. The aryl example gives lower yields partly because of ring metalation. 

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