Hydroxy ketones with sulfur

Electron-deficient alkenes add stereospecifically to 4-hydroxy-THISs with formation of endo-cycloadducts. Only with methylvinyl-ketone considerable amounts of the exo isomer are produced (Scheme 8) (16). The adducts (6) may extrude hydrogen sulfide on heating with methoxide producing 2-pyridones. The base is unnecessary with fumaronitrile adducts. The alternative elimination of isocyanate Or sulfur may be controlled using 7 as the dipolarenOphile. The cycloaddition produces two products, 8a (R = H, R = COOMe) and 8b (R = COOMe, R =H) (Scheme 9) (17). Pyrolysis of 8b leads to extrusion of furan and isocyanate to give a thiophene. The alternative S-elimi-nation can be effected by oxidation of the adduct and subsequent pyrolysis. 

A iD-Corticoids have been important intermediates since it was shown ° that substitution at C-9 enhances anti-inflammatory activity. These olefins are usually obtained from 11a- or 11)5-alcohols, and consequently several refined methods have been devised for effecting this dehydration. It is desirable that such methods be compatible with the presence of A" -3-ketone and 17-hydroxy functions. The first direct procedure for which high yields were claimed was described in a patent issued to Upjohn. According to this method, the alcohol (11a or )5) is treated first with A-bromoacetamide in pyridine, then with sulfur dioxide. Recently it has been claimed " that the A-haloamide/sulfur dioxide method gives results superior to other methods, although the methanesulfonyl chloride/sulfur dioxide procedure (see below) apparently was not compared (see also ref. 94). 

Aliphatic a-hydroxy ketones react with sulfur tetrafluoride, generally to provide trifluoroal-kanes. However, under carefully chosen conditions the carbonyl group in hydroxy ketones remains intact while the hydroxy group undergoes selective substitution by fluorine. Thus, 5-hydroxyoctan-4-one reacts with sulfur tetrafluoride (20°C, 3 h) to give a 1 1 mixture of 5-fluorooctan-4-one(l b) and 2-oxo-l-propylpentyl fluorosulfite.63 a-Fluoro ketones 1 are formed in high yield and as the sole product when diethyl ether is used as solvent.64... 

A general type of [3 + 3] heterocyclization involves initial nucleophilic attack on the electrophilic three-membered heterocycle by a 1,3-electrophile-nucleophile. Aziridines (330) with either a-mercapto ketones (329) or with a mixture of a ketone and sulfur give 5,6-dihydro-1,4-thiazines (330 — 331 — 332). Azirines (333) can be used for the preparation of pyrazinones (334) from ot-amino esters R2CH(NH2)C02Et and of 1,4-oxazinones from a-hydroxy esters (83TL1153). 

On treatment with sulfur tetrafluoride at 20 °C, aliphatic a-hydroxy ketones afford mixtures of a,p,P-tnfluoroalkanes, difluoroalkylsulfites, and bis(difluo-roalkyl)sulfates [182]... 

Torok et al. observed that 12 is selectively hydrogenated to the corresponding hydroxy ketone over amorphous Ni-P and Ni-B catalysts in ethanol at 120°C and 7 MPa H2, while over Raney Ni the corresponding diol was obtained and over Ni-P foil, treated with sulfuric acid during its preparation, the ring-opened product 14 (ethyl ester) was... 

DAST (1) and the related aminofluoro-/ -sulfanes convert primary, secondary, tertiary, allylic and benzylic alcohols into fluorides under mild conditions in high yield with little byproduct formation. In this respect they are superior to most other fluorinating agents. DAST (1) and other aminofluoro-2 -sulfanes can fluorinatc hydroxy acids and hydroxy ketones selectively to give the corresponding fluoro acids and fluoro ketones, which is impossible or, at least, diflicult w ith sulfur tetrafluoride. 

In another instance, the action of aliphatic Grignard reagents on methyl a-nitrosoethyl ketone with subsequent acid hydrolysis furnishes a-hydroxy ketones of the type CHj(R)COHCOCHj." The oxime of 1-methylcyclo-penten-5-one is hydrolyzed by dilute sulfuric acid (54%). It is prepared by the action of nitrosyl chloride on 1-methylcyclopentene with subsequent dehydrohalogenation with pyridine. ... 

When urea (or thiourea) reacts with a-hydroxy ketones or a-diketones the products are imidazolin-2-ones (or -thiones) (70AHC(12)103,66RCR122). The reaction is limited to the preparation of 4,5-alkyl(or aryl)- or l,4,5-trialkyl(or triaryl)-imidazoles since an oxygen or sulfur function appears at C-2. Benzoin condenses with iV-phenylthiourea in hexanol in the presence of catalytic quantities of HCl to give l,4,5-triphenylimidazoline-2-thione (131) in 50-60% yield (Scheme 69). While 1-methylurea can also take part in the reaction. 

Hoffman et al. investigated the reactions of a-nosyl ketones with different nucleophiles (86JOC51). When the nonnucleophilic DBU was applied as base, unique rearrangements of a-nosyl ketones (100) were observed. Reaction of 100 with DBU in benzene gave a-hydroxy-a-(4-nitrophenyl) ketones 103 via enolates 101 and presumed four-membered ring intermediates 102. The latter (102) open to afford sulfur dioxide and 103. The same products were also obtained with DBN. 

The maiin domain of oxidation with dimethyl sulfoxide is the conver-sionofprimary alcoholsinto aldehydes andofsecondaryalcoholsintoketones. These reactions are accomplished under very mild conditions, sometimes at temperatures well below 0 °C. The reactions require the presence of acid catalysts such as acetic anhydride [713, 1008, 1009], trifluoroacetic acid [1010], trifluoroacetic anhydride [1011, 1012, 1013], trifluorometh-anesulfonic acid [1014], phosphoric acid [1015, 1016], phosphorus pentox-ide [1006, 1017], hydrobromic acid [1001], sulfur trioxide [1018], chlorine [1019, 1020], A -bromosuccinimide [997], carbonyl chloride (phosgene) [1021], and oxalyl chloride (the Swem oxidation) [1022, 1023, 1024], Dimethyl sulfoxide also converts sufficiently reactive halogen derivatives. into aldehydes or ketones [998, 999] and epoxides to a-hydroxy ketones at -78 °C [1014]. 

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