Diethyl mesylation

It has been found that reactions of diethyl mesyl- or tosyloxybenzyl-phos-phonates (272) with sodium diethyl phosphite give the corresponding... 

The enantiomerically pure indolizidine (—)-422 has been synthesized starting from L-malic acid diethyl ester 407. The hydroxyl function of L-malic acid diethyl ester 407 has been protected as dihydropyranyl ether 408 with 2/7-dihydropyran and Amberlyst 15 in pentane at room temperature. The diethyl ester 408 was then reduced with lithium aluminium hydride in diethyl ether under reflux and the newly generated hydroxyl functions then protected with mesyl chloride in the presence of triethylamine in dichloromethane at 0°C. This was converted into newly protected pyrroline nitrone 409 in 44% overall yield through a well-established method (Scheme 90). The regio-isomeric 5-pyrroline-iV-oxide 410 formed in 4% overall yield was easily separated by column chromatography <20000L2475>. 

The mesylate salt is formed by dissolving the free base in methanol and by adding methanesulfonic acid (1 eq). The solution is diluted with diethyl ether until the salt crystallizes out of solution. The crystals are collected and dried to afford the mesyl salt of the title compound, MP 215°-216°C. 

When 4-dodecylbenzenesulfonyl azide is used for the diazo transfer reaction, the crude reaction product is contaminated with by-products that cannot be separated during basic workup, and consequently column chromatography is required lor the purification of the diazo ketone. Use of mesyl azide for the diazo transfer reaction allows purification of the crude reaction product by recrystallization from diethyl ether-pentane to obtain 10.11 g (86%) of the desired diazo ketone. 

Most the diethyl 5- and 6-formylalkylphosphonates incorporating an ort/zo-substituted aromatic ring having a masked aldehyde group are obtained by direct displacement reactions employing Michaelis-Becker attack at alkyl halides or mesylates. For example, ort/zo-methylbenzyl alcohol is elaborated to masked aldehyde in low yield by treatment with n-BuLi and alkylation of the... 

Creary, X., Geiger, C.C., and Hilton, K., Mesylate derivatives of a-hydroxy phosphonates. Formation of carbocations adjacent to the diethyl phosphonate group, J. Am. Chem. Soc., 105, 2851, 1983. 

Reduction of phenols [1, 252, after citation of ref. 3]. In achieving the synthesis of triptindane (11), Thompson obtained the methyl ether (8a) as an intermediate, demethylated it to (9), and effected deoxygenation to (11) by the method of Kenner and Williams consisting in reaction with diethyl phosphonate or mesyl chloride and reduction of the diethyl phosphate or the mesylate ester with sodium in liquid ammonia yields, first procedure 58% second procedure 36%. 

For deoxygenation of a phenol by conversion into the mesylate or diethyl phosphate and reduction with sodium and ammonia, see Diethyl phosphonate (both volumes). 

Chlorination /-Butylhypochlorite. Catechyl phosphorus trichloride. N-Chlorosuccinimide. Cupric chloride. N,N-Diethyl-l,2,2-trichlorovinylamine. Iodobenzene dichloride. Mesyl chloride. Sulfuryl chloride. 

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