Sulfur trioxide-pyridine complex/DMSO

The use of dimethyl sulfoxide-acetic anhydride as a reagent for the oxidation of unhindered steroidal alcohols does not appear to be as promising due to extensive formation of by-products. However, the reagent is sufficiently reactive to oxidize the hindered 11 j -hydroxyl group to the 11-ketone in moderate yield. The use of sulfur trioxide-pyridine complex in dimethyl sulfoxide has also been reported. The results parallel those using DCC-DMSO but reaction times are much shorter and the work-up is more facile since the separation of dicyclohexylurea is not necessary. Allylic alcohols can be oxidized by this procedure without significant side reactions. 

A total of 10.0 g (8.9 mmol) SASRIN resin2 (note 1) was washed with N,N-dimethyIfonnamide (DMF 2 x 25 mL), methanol (MeOH 2 x 25 mL), and dichloromethane (DCM note 2 2 x 25 mL), and dried under vacuum (0.5 torr) at 70°C overnight. To a suspension of the dried SASRIN resin in lOOmL of methyl sulfoxide (DMSO note 2) and 25 mL of DCM was added 12.4 mL (89 mmol, 10.0 Eq.) triethylamine (note 2) followed by 7.1 g (44.5 mmol, 5.0 Eq.) sulfur trioxide-pyridine complex (note 2). The suspension was shaken on a radial arm at room temperature overnight (note 3) filtered on a glass frit and washed with DCM (3 x 100mL), DMSO (3 x lOOmL), DCM (3 x lOOmL), and tetrahydrofuran (THF 3 x 100 mL) and dried under vacuum (0.5 torr) at room temperature to give 10.0 g Ameba resin (notes 4 and 5). 

DCM (anhydrous), DMSO (anhydrous), triethylamine (99 + %), sulfur trioxide-pyridine complex, DMA (anhydrous), potassium tert-butoxide (95%), DCE (anhydrous), 2-(4-methoxyphenyl)ethylamine (98 + %), sodium triacetoxy-borohydride (95%), A/A-diisopropylethylamine (99%), p-toluenesulfonyl chloride (99 + %), and trifluoroacetic acid (99 + %) were obtained from Aldrich Chemical Company, Inc. 4-Hydroxy-2-methoxybenzaldehyde (>98%) was obtained from Fluka Chemie, AG. 

Goh and Harvey effected the oxidation of the m-diol (3) to the o-quinone (4) efficiently by use of the sulfur trioxide-pyridine complex in DMSO-triethylamine. Use of DMSO-acetic anhydride (I, 305 2, 163-165 3,121-122) gave fair, but erratic yields of the quinones. Other reagents were completely unsuccessful. Note that oxidation... 

There are several methods reported in the literature for transforming vicinal diols into ct-diketones while avoiding the risk of C-C bond cleavage.26 Examples include the standard Swem conditions (dimethyl sulfoxide and oxalyl chloride followed by triethylamine), or the use of DMSO activated by acetic anhydride, pyridine-sulfur trioxide complex, or dicyclohexylcarbodiimide (Mq/J-att oxidation). Diones are also obtained by treatment with benzalacetone as a hydride acceptor in the presence of catalytic amounts of tris(triphenylphosphine)ruthenium dichlonde [(PPh RuCFl.27 Recent developments include the use of w-iodoxyben/.oic acid28 or the oxoammonium salt of 4-acctamidoletramethylpipcridine-1-oxyl and y -toluencNulfonic acid.29... 

Parikh and Doering in 1967 described80 that DMSO can be activated for the oxidation of alcohols, using sulfur trioxide that can be conveniently added to the reaction mixture as complex with pyridine. According to the original... 

In the first step of this reaction sequence, the primary alcohol 21 is oxidized to the corresponding aldehyde 38 in a Parikh-Doering oxidation which is related to the Swern oxidation. In general, this type of oxidation is conveniently carried out by addition of a solution of pyridine-SOs complex in DMSO to a mixture of the alcohol, DMSO and NEts. It can be assumed that dimethyl sulfoxide and sulfur trioxide react to form 0-dimethylsulfoxonium sulfate 40, which then further reacts with primary alcohol 39 to give 0-alkyl dimethylsulf-oxonium intermediate 41. Then, sulfonium salt 42 is formed and subsequently deprotonated by NEts to give sulfonium ylide 43. Finally, an intramolecular p-elimination occurs to provide the desired aldehyde 44 and dimethyl sulfide. 

Oxidizing agent. Parikh and Doering10 report a novel reagent consisting of sulfur trioxide, conveniently in the form of the pyridine complex, and DMSO in the presence of triethylamine. The reagent oxidizes primary and secondary alcohols to aldehydes and ketones rapidly at room temperature. It oxidizes allylic alcohols to the corresponding a -unsaturated carbonyl compounds. 

Dimethyl sulfoxide-Sulfur trioxide [1, 309, before references]. The combination of DMSO and sulfur trioxide, in the form of the pyridine complex, in the presence of trimethylamine oxidizes primary and secondary alcohols in good yield to aldehydes and ketones, respectively.55 The reaction usually is complete within minutes and the products are isolated by acidification and precipitation with water. The reagent also oxidizes allylic alcohols to the corresponding a,fi-unsaturated carbonyl compounds. One advantage over the DMSO-DCC method is that the elaborate purification required when dicyclohexylurea is a product can be dispensed with. Testosterone, with a 17/3-hydroxyl group, was oxidized toA -androstene-3,17-dione very rapidly the 17-epimer required a period of 35 min. 

The complex formed by pyridine-sulfur trioxide was shown to activate DMSO for oxidation, when a base such as triethylamine is present.The presumed intermediate is 72. Reaction of the alcohol generates the usual complex (52). Deprotonation by triethylamine gives 65, and this gives the carbonyl product. Stereo-... 

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