1.2- Ditosylates ketones

Axenrod and co-workers reported a synthesis of TNAZ (18) starting from 3-amino-l,2-propanediol (28). Treatment of (28) with two equivalents of p-toluenesulfonyl chloride in the presence of pyridine yields the ditosylate (29), which on further protection as a TBS derivative, followed by treatment with lithium hydride in THF, induces ring closure to the azetidine (31) in excellent yield. Removal of the TBS protecting group from (31) with acetic acid at elevated temperature is followed by oxidation of the alcohol (32) to the ketone (33). Treatment of the ketone (33) with hydroxylamine hydrochloride in aqueous sodium acetate yields the oxime (34). The synthesis of TNAZ (18) is completed on treatment of the oxime (34) with pure nitric acid in methylene chloride, a reaction leading to oxidation-nitration of the oxime group to em-dinitro functionality and nitrolysis of the A-tosyl bond. This synthesis provides TNAZ in yields of 17-21 % over the seven steps. 

Vinylic and aryl halides can be used to vinylate or arylate carboxylic esters (but not ketones) by the use of NiBr2 as a catalyst.1463 However, ketones have been vinylated by treating their enol acetates with vinylic bromides in the presence of a Pd compound catalyst.1464 Also as in 0-94, this reaction can be used to close rings.1465 In one example of this, rings have been closed by treating a diion of a dialkyl succinate with a l,cu-dihalide or ditosylate,1466, e.g. ... 

The progress of the reaction can be monitored by TLC by working up a sample of the reaction mixture filter through Celite, cool to 0°C, and acidify to pH 1 with 10% aqueous HCI. The solid that precipitates is isolated by filtration and dissolved in dimethylformamide (DMF) for TLC analysis on Merck precoated-silica gel 60 plates with methyl ethyl ketone-methanol-water (4 1 1) as eluent, developed by dipping in 5% sulfuric acid-ethanol and heated to 450°C (e.g., with a Bunsen burner). Rf values are 0.25 for fl-cyclodextrin, 0.5 for monotosylate and 0.65 for a second product, probably ditosylate. 

Dihalides and 1,5-ditosylates have been used for the preparation of fully-saturated monocyclic 1,2-diazepines 165 (Scheme 83). 5-Halo-aldehydes and 5-halo-ketones react with a wide range of substituted hydrazines to give 4,5,6,7-tetrahydro-l,2-diazepines 166 <1976H(4)1509>. The reaction of 1,5-diketones with hydrazine has been much used as a source of 5,6-dihydro-4/7- 1,2-diazepines 167 . 

Elimination. An improved synthesis of unsaturated pyranosides by elimination of v(c-ditosylates is mediated by Zn-Nal with microwave heating. Under such conditions higher yields and faster rates are observed. Dechlorination of jS-chloro-jS-(chlorodifluoromethyl)vinyl ketones to afford difluoroallyl ketones is effected with assistance of ultrasound. ... 

Dithiins.—A new synthesis of 1,3-dithiins from aromatic aldehydes, acetylenes, and HjS has been described. Carbenoids react with 1,2-dithia-acenaphthene to afford the insertion product (22 R = Ph or tosyl). Pyrolysis of the ditosyl derivative yields the ketone (22 RR = O). 

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