Alkyl methanesulfonates, reduction

In contrast to the anion of diethyl phosphoramidate or trifluoromethanesulfonamide, which cannot be cleanly monoalkylated, - the anion of trifluoroacetamide (100) was monoalkylated by alkyl halides or alkyl methanesulfonate. The resulting A -alkylamides (101) were converted into primary amines by alkaline hydrolysis or reduction (NuBHa Scheme 42). Various primary amines were prepared from (100) with primary alkyl iodides or methanesulfonate, benzyl and allyl halides, a-bromocarbonyl compounds and 2,4-dinitrochlorobenzene. However, competitive elimination is a serious side reaction for less reactive primary alkyl chlorides and secondary halides or methanesulfonate. The synthesis of secondary amines from (100) has also been reported. ... 

Interestingly, treatment of diene 215a with methanesulfonic acid afforded 216 as a single diastereomer in 88% yield, the structure of which was confirmed by X-ray analysis (Scheme 60). The transformation of 216 into 217 started with an alkylation, followed by reductive desulfurization and triazene formation to afford compound 217 in 92% yield. Upon treatment with diiodomethane, triazene 217 was smoothly converted to aryl iodide 218 in 75% yield. Pd-catalyzed intramolecular Heck coupling of 218 led to the desired product 219b in 62% yield. 

The selective reduction of cyclic imidates (63) to the aldehyde oxidation level has been demonstrated by Shono et al. As shown in Scheme 19, the imidate is first alkylated on nitrogen and then reduced electrolytically in DMF in the presence of methanesulfonic acid. Unfortunately the scope of the method is unclear, as the main purpose of the work was to generate intermediate (64) in the presence of alkylating agents, leading to 2,2-disubstituted imidazolidines. Nonetheless, it was reported that decanal and dodecanal could be obtained in 82% and 70% yields, respectively. 

The final example in this section is classed as a 1,3-dipolar addition, as this is the key step in the reaction, although actual formation of the pyrrolizidine ring is by an intramolecular alkylation process. Tufariello and Tette showed that A -pyrroline-N-oxide added regioselectively in a 1,3-dipolar fashion to the dipolarophile to give an isoxazolidine (95) in 80% yield [Eq. (27)]. The pyrrolizidine ring was then formed by hydrogenolysis of the methanesulfonate derivative of 95 in 95% yield. The dehydration and reduction steps were not so efficient, and a mixture of reduction products was obtained. Half of this mixture was ( )-supinidine (96) and the remainder consisted of fully reduced isomeric 1-hydroxymethylpyrrolizidines. 

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