Sulfonyl Chlorides and Anhydrides

6 Sulfonyl Chlorides and Anhydrides Methanesulfonyl chloride (MsCI) 

A stereoselective construction of the taxane BC substructure requires an intermediate isocyano function in 1662, which is obtained in 100% yield from the formamide 1661 by dehydration with mesyl chloride [1232], 

Typical procedure. Isocyanide 1662 [1232] To a solution of 1661 (227 mg, 1 mmol) in pyridine at 0 °C under argon, mesyl chloride (0.155 mL, 2 mmol) was added dropwise. After stirring at the same temperature for 1 h and then at room temperature for 4 h, the reaction mixture was diluted with dichloromethane, washed with aqueous 0.5 n hydrochloric acid and water, dried (Na2S04), and passed through a short column of silica gel. Removal of the solvent left 258 mg (100%) of 1662 as a waxy solid mp 85-89 °C IR (neat) v ax = 2150, 1710 cm h 

A total synthesis of the sesquiterpenoids (-)-axamide-4 1663 and (—)-axisonitrile-4 1664, affording both natural products, has been accomplished in eleven steps [1233]. From the view of a chemist, it is remarkable that both the isocyanide and its chemical precursor molecule formamide are naturally occurring. The transformation of (—)-axamide-4 into (—)-axisonitrile-4 is carried out with p-tosyl chloride in 94% yield. 

Typical procedure. dl-Axisonitrile-4 1664 [1234] To a solution of dl-axamide-4 1663 (344 mg, 1.39 mmol) in dry pyridine (5 mL), p-tosyl chloride (535 mg, 2.8 mmol) was added at room temperature. The mixture was stirred at room temperature for 15 h, then cooled to 0 °C and crushed ice (3 g) was added. The resulting mixture was stirred at 0 °C for 30 min, diluted with petroleum ether/diethyl ether, (1 1 50 mL), and washed with brine (3 x 10 mL). The combined aqueous layers were extracted with petroleum ether (3 x 15 mL), and the combined organic layers were dried (Na2S04) and concentrated in vacuo. The residue was chromatographed on 30 g of silica gel (eluting with petroleum ether, bp 35-60 °C) to give 0.32 g (100%) of dl-axisonitrile-4 1664 as a pale-yellow solid mp 61-63 °C. 

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Obtained by computer simulation using parameters initially calculated from analytical expressions derived from a simplified scheme (ignoring k5 and k6 terms) and then modified fitting (least squares) to a computer simulation of the full reaction scheme. Values for A12/A4, kjk7, 11/ 4, and ko/klo were obtained in this way from the sulfonylammonium salt and bromomethanesulfinate results these parameters were held constant while k2tkx and k3fk were optimized for the reactions of the sulfonyl chloride and anhydride. 

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