Mannopyranosides with butyllithium

Dialkyl methyl phosphonate derivatives 37a-c of mannopyranosides may be prepared from cyclic sulfate 36 by reaction with the appropriate lithiated methylphosphonate, prepared by titration of the corresponding methyl-phosphonate with butyllithium in the presence of 1,1-diphenylethylene as indicator (Equation 4) <2002TL4017>. 

Given the availability of compound 18 from the reaction of methyl di-O-benzylidene-D-mannopyranoside 113 with butyllithium [154,155], we reasoned that the intermediate enolate 114 should be sufficiently stable to be alkylated at low temperature (Scheme 39). We... 

Klemer and Rodemeyer (ref. 33) showed that the reaction of the dibenzylidinated mannopyranoside 38 with butyllithium led to ketone 40a (Scheme 8). The enolate 39 was postulated as an intermediate and this has been established subsequently in our laboratory (ref. 34) and Chapleur s (ref. 35) by in situ alkylation to give 40c. We established, indirectly, that alkylation gave axial adduct 40b, with subsequent epimerization to 40c, by means of a second alkylation of the latter, which led to the stereoisomer 40d, exclusively. Thus, the alkylation of enolate 39 occurs from the 3-face (ref. 36). 

This section is completed with a brief review of the synthesis and properties of this epimer (20) of the precursor of thiazole in bacteria. This pentulose is conveniently accessible by an unconventional route (Scheme 19). Methyl 2,3 4,6-di-O-isopropylidene-a-D-mannopyranoside, readily available from methyl ot-D-mannopyranoside, is converted to the ketonic glycoside by butyllithium in 91% yield, following a method first published by Klemer and Rodemeyer43 and scaled up by Horton and Weckerle.44 This was converted by means of lithium hydroxide in a water-ether mixture into 3,5-0-benzylidene-l-deoxy-D-eryf/iro-2-pen-tulose in 55% yield. Hydrolysis to the free pentulose (20) proceeded in 73% yield in aqueous acetic acid. This product was obtained as a syrup with a characteristic absorption band at 1705 cm 1 as a film. Thus, there is a fair proportion of the open-chain ketone under these conditions, as with the D-threo epimer.45... 

Carbohydrate derivs. Methyl 2,3 4,6-di-0-benzylidene-oc-D-mannopyranoside in abs. tetrahydrofuran treated at -30° under Ng with 2 moles -butyllithium in n-hexane, and the product isolated after 0.5 hr. -> methyl 4,6-0-benzylidene-2-deoxy-a-D-eryr/zro-hexopyranosid-3-ulose. Y ca. 70%. A. Klemer and G. Rode-meyer, B. 107, 2612 (1974). 

The vinyl triflate 37 is readily formed from methyl 2,3 4,6-di-0-ben2ylidene-a-D-mannopyranoside by treatment with n-butyllithium then. Y-phenyltrifluoromethanesulfonimide (PhNTf2). (See Chapter 14 for its use in preparing branched-chain sugars)... 

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