Methanesulfonates, reduction

Its production was 621 t and the average price 0.75/kg in 1987. Direct YeUow 44 (64) is prepared by phosgenation of an equimolar mixture of metanilic acid coupled to o-anisidinomethanesulfonic acid (with subsequent hydrolysis of the methanesulfonic acid group) and nitro aniline coupled to sahcychc acid (with subsequent reduction of the nitro group). 

Cyclization of the Weinreb amide 356 under reductive conditions using lithium aluminium hydride (LAH) led to formation of the carbinolamine 357 which underwent elimination on treatment with methanesulfonic acid to give 358 in 72% yield as shown in Scheme 27 <2005TL249>. 

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. 

An example of an alcohol that can undergo rapid skeletal rearrangement is 3,3-dimethyl-2-phenyl-2-butanol (Eq. 29). Attempts to reduce this alcohol in dichloromethane solution with l-naphthyl(phenyl)methylsilane yield only a mixture of the rearranged elimination products 3,3-dimethyl-2-phenyl-l-butene and 2,3-dimethy 1-3-phenyl-1 -butene when trifluoroacetic acid or methanesulfonic acid is used. Use of a 1 1 triflic acid/triflic anhydride mixture with a 50 mol% excess of the silane gives good yields of the unrearranged reduction product 3,3-dimethyl-2-phenylbutane, but also causes extensive decomposition of the silane.126 In contrast, introduction of boron trifluoride gas into a dichloromethane solution of the alcohol and a 10 mol% excess of the silane... 

A variety of para-substituted 2-phenyl-2-butanols undergo quick and efficient reductions to the corresponding 2-phenylbutanes when they are dissolved in dichloromethane and a 2-10% excess of phenylmethylneopentylsilane and boron trifluoride is introduced at 0° (Eq. 30).126 Several reactions deserve mention. For example, when R = CF3, use of trifluoroacetic acid produces no hydrocarbon product, even after two hours of reaction time. In contrast, addition of boron trifluoride catalyst provides an 80% yield of product after only two minutes. When R = MeO, both trifluoroacetic acid and boron trifluoride produce a quantitative yield of the hydrocarbon within two minutes. However, when R = NO2, attempts to promote the reduction with either trifluoroacetic acid or even methanesulfonic acid fail even after reaction periods of up to eight hours, only recovered starting alcohol is obtained. Use of boron trifluoride provides a quantitative conversion into 2-(/ -nitrophenyl)butane after only ten minutes. It is significant that the normally easily reducible nitro group survives these conditions entirely intact.126129 Triethylsilane may be used as the silane.143... 

Asymmetric reduction of dialkyl ketones. The borohydride 1 reduces dialkyl ketones with low enantioselectivity. However, treatment of the lithium dihydri-doborate 2 with methanesulfonic acid provides Reagent I, which consists of 1 equiv. of R,R-1 and 0.2 equiv. of 2,5-dimethylborolanyl mesylate, which serves as a... 

The use of the zinc-copper couple to effect the reduction of the methanesulfonate 168 with rearrangement furnished 169 (Scheme 20.34) [10]. Treatment of 168 with methylmagnesium bromide in the presence of copper(I) cyanide to induce an SN2 -type reaction produced the methylated adduct 170. The half-life of the Myers-Saito cyclization of 169 is 66 h at 37 °C, whereas that of 170 is 100 min. The faster rate of cyclization for 170 has been attributed to a steric effect favoring the requisite s-cis or twisted s-cis conformation. 

Cleavage of C—O bonds by direct electron transfer from a cathode is usually difficult because of the negative reduction potential of the bond. Therefore, the reduction of aliphatic alcohols (R-OH) to the corresponding hydrocarbons (R-H) is often carried out by the transformation of hydroxyl groups to good leaving groups such as halides (X = Br, I), methanesulfonates (OMs), and... 

Scheme 166 Desoxygenation of a-hydroxyesters via reduction of the methanesulfonates with diphenyidiselenide as mediator.

Methanethiol is generated as a side-product by the reduction of the methanesulfonate with diisobutylaluminum hydride. 

Reduction of amides is an important preparative method for the synthesis of primary amines. Reducing agents used for this purpose include lithium aluminum hydride, sodium borohydride, triphenyl-phosphine (Staudinger reduction), and thiols. In the present case it is important to consider the compatibility of the reduction system with the carboxylic and methanesulfonic acid functions. Platinum and palladium arc often used for catalytic reduction. 

Electrochemical reduction of imines (25 Schiff bases) in acidic media proceeds via the iminium species, i.e. the protonated imine (26) (Scheme 5)29. Since 26 bears a positive charge, it is very easily reduced, so much so that the resulting neutral radical (27) is formed at a potential positive of its reduction potential. The products are therefore derived from 27 rather than the corresponding carbanion (28). This stands in contrast with the electrochemical behavior of imines in neutral media, where 27 is immediately reduced to 2830. Thus, cathodic reduction of /u. s-irnincs of 1,2-diamines (29) in DMF containing methanesulfonic acid affords tetrahydropyrazines (equation 13)31. A similar reaction can... 

Reduction of amides. Sodium borohydride combined with methanesulfonic acid in DMSO reduces amides to the corresponding amines in 60-90% isolated yield. I he system also reduces acids and esters to primary alcohols. These reductions have been conducted with lithium aluminum hydride and with borane-tetrahydrofurane (5,48),2 hut with somewhat different selectivities. This new reagent, however, appears to be less hazardous than the latter reagent. 

Methyl 4,6-0-benzylidene-3-deoxy-a-D-ribo-hexopyranoside (56) was benzoylated, debenzylidenated, and partially p-toluenesulfon-ylated to 57 this was converted into 58 by reaction with sodium iodide, followed by catalytic reduction. The methanesulfonate of 58 was converted into 59 by reaction with sodium azide in N,N-dimethylformamide, and 59 was converted into 4-azido-3,4,6-trideoxy-a-D-xylo-hexose (60) by acetolysis followed by alkaline hydrolysis. Reduction of 60 with borohydride in methanol afforded 61, which was converted into 62 by successive condensation with acetone, meth-anesulfonylation, and azide exchange. The 4,5-diazido-3,4,5,6-tetra-deoxy-l,2-0-isopropylidene-L-ara/uno-hexitol (62) was reduced with hydrogen in the presence of Raney nickel, the resultant diamine was treated with phosgene in the presence of sodium carbonate, and the product was hydrolyzed under acidic conditions to give 63. The overall yield of 63 from 56 was 4%. The next three reactions (with sodium periodate, the Wittig reaction, and catalytic reduction) were performed without characterization of the intermediate products, and gave (+)-dethiobiotin methyl ester indistinguishable from an authentic sample thereof prepared from (+)-biotin methyl ester. 

A difference in the behavior of methanesulfonic and p-toluenesul-fonic esters of 1,3-0-benzylidene-tetritols on reduction with lithium aluminum hydride in tetrahydrofuran has been described by Foster and coworkers 1,3-0 -benzylidene -2,4 - di - O - p - tolylsulfonyl - L -erythritol and -L-threitol gave the corresponding 4-deoxytetritol acetals, whereas l,3-0-benzylidene-2,4-di-0-(methylsulfonyl)-L-threitol was simply demethanesulfonylated to 1,3-O-benzylidene-L-threitol. 

Asymmetric Reduction of Ketones. A reagent system consisting of (/ ,/ )-2,5-dimethylborolane (1.0 equiv) and the corresponding borolanyl mesylate (0.2 equiv) reduces a variety of prochiral ketones with asymmetric induction in the range of 80-100% ee. The reagent system is prepared in situ by addition of 1.4 equiv of Methanesulfonic Acid to a solution of the lithium dihydridoborate, prepared as in eq 5 above (eq 7). 

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. 

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