Thiomethyl ketones

A total synthesis of (+)-paspalicine and (+)-paspalinine took advantage of the Gassman indole synthesis. The thiomethyl ketone was treated with A-chloroaniline (prepared by mixing aniline with t-butyl hypochlorite) to afford the azasulfonium salt, which was transformed into anilinylsulfide upon treatment with triethylamine. Desulfurization with Raney nickel was followed by the acid-catalyzed cyclization to give the hexacyclic indole intermediate. 

The silylmethylsulphurane MeaSiCH—SMcj thiomethylates ketones to give products dependent upon the substituents on the ketone and their reaction conditions [equation (24)]. Five different reaction pathways have been found to exist. ... 

The cyclization of y -hydroxy ketones is useful for the formation of pyrans,306,403 both directly and via rearrangement, as illustrated in Eq. 231.153 As with their acyclic counterparts, these cyclizations also occur with the silyl ethers of the hydroxy ketones where Et3SiH/BiBr3 is used with the TBS and TES ethers.342,404 A methyl thiomethyl ether is also capable of undergoing the reductive cyclization 405 In like manner, 1,4-diols and e-hydroxy ketones provide oxepanes, with I ds Si H or PhMe2SiH/TMSOTf being especially effective (Eqs. 232 and 233).336,406 The trimethylsilyl ether of the alcohol also provides the oxepane.306... 

This is another example of umpolung (see 0-95) 1478 the normally electrophilic carbon of the aldehyde is made to behave as a nucleophile. The reaction can be applied to the unsubstituted dithiane (R = H) and one or two alkyl groups can be introduced, so a wide variety of aldehydes and ketones can be made starting with formaldehyde.1504 R may be primary or secondary alkyl or benzylic. Iodides give the best results. The reaction has been used to close rings.1505 A similar synthesis of aldehydes can be performed starting with ethyl ethyl-thiomethyl sulfoxide EtSOCH2SEt.1506... 

By introducing a thiomethyl substituent at the terminal position of 5 it was possible to direct attack to this position exclusively (61,103). Introduction of bulky 1,5-trimethylsilyl substituents into a pentadienyllithium provides a way of getting selective attack at C-3 (62). This approach worked with acetone, cyclohexanone, acetaldehyde, and 2-methylpropanal. With diisopropyl ketone, however, addition at C-3 still occurred, followed by Peterson elimination, giving a novel synthesis of 1,3,5-trienes (104) [Eq. (6)]. 

Alkoxymethyl and Thiomethyl Dipeptidyl Ketone-Based Inhibitors... 

In a similar vein, the adducts derived from the anion of methoxymethyl phenyl sulfone and cyclic ketones rearrange on Lewis acid catalysis (Scheme 13). This rearrangement is quite stereospecific, in that a single diastereoisomer is formed and it is the most substituted group which migrates. Similar results were obtained with adducts derived from phenyl thiomethyl phenyl sulfone (Scheme 14). ... 

When a 2-thiomethyl-l,3-selenothiolium iodide such as (84) reacts with an aryl ketone (85) in pyridine-acetic acid, fulvenes such as (86) are obtained reaction with a Wittig-Homer reagent takes place at both carbonyl groups (Equation (8)) <90PAC473,91JCS(Pl)157>. 

The starting material, l,3-dibenzyloxy-2-propanol 265, is easily oxidized to the ketone 408 using N-chlorosuccinimide and dimethyl sulfide. Compound 408 was smoothly converted into the epoxide 409. The epoxide ring was opened by the attack of benzylate anion at the least hindered site to produce 2-benzyloxymethyl-l,3-dibenzyloxy-2-propanol (410), which was activated as the thiomethyl ether system 411 using acetic anhydride in DMSO. The thiomethyl ether is readily activated by iodine, allowing nucleophilic attack at the methylene position. As a result, compound 411 was... 

Methyl Methylthiomethyl Sulfone. Methyl methyl-thiomethyl sulfone is the 5-methyl analog of MT-sulfone and it is conveniently synthesized by oxidation of methyl methylthiomethyl sulfoxide (FAMSO) with potassium permanganate or H202-Na0H. It is useful for synthetic methods similar to those using MT-sulfone synthesis of carboxylic esters, ketones, and a-aLkoxy- -arylacetates. In the reaction of this reagent with allylic bromides, a-methylthio- /,5-unsaturated sulfones are obtained by stirring the bromide with potassium carbonate and potassium iodide in hexamethylphosphoric triamide (eq 14), which does not occur with MT-sulfone. 

Seebach has described in detail the alternative preparation of cyclobutanones via oxaspiropentane intermediates/ 1-Bromo-l-lithiocyclopropanes react with ketones or aldehydes to give bromohydrins (259) which are readily converted via oxaspiro-pentanes (260) to cyclobutanones. A variety of examples are described. Overall yields vary somewhat with substitution pattern, but can be as high as 90% in the most favourable cases. A variation of the sequence is the conversion of the dibromocyclo-propane into its 1-bromo-l-thiomethyl derivative before lithiation and reaction with a carbonyl partner. As dibromocyclopropanes are readily available from the addition of dibromocarbene to olefins, this sequence affords a useful method of annelat-ing cyclobutanones to olefins, and is complementary to the Trost secoalkylation procedure. 

New syntheses of enamino-ketones by the ring-opening of isoxazoles with samarium di-iodide and with pentacarbonyliron, by the reaction of 2-alkyl-thiomethyl-3-alkylthioacrylophenones with amines, and by the intramolecular photoarylation of A -[2-(haloaryl)ethyl]-(3-enaminones, of enamino-diketones by the reaction of (3-chlorosulphonic acid chlorides with amines and by amino-methylenation of cyclic (3-dicarbonyl compounds, and of enamino-esters by aminomethylenation of esters and lactones and by the reaction of nitriles with magnesium enolates have been reported. 

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