Esters sodium borohydride

Sodium borohydride reduces esters but the reaction is too slow to be useful Hydrogenation of esters requires a special catalyst and extremely high pressures and tern peratures it is used m industrial settings but rarely m the laboratory... 

Lithium borohydride is a more powerful reducing agent than sodium borohydride, but not as powerful as lithium aluminum hydride (Table 6). In contrast to sodium borohydride, the lithium salt, ia general, reduces esters to the corresponding primary alcohol ia refluxing ethers. An equimolar mixture of sodium or potassium borohydride and a lithium haUde can also be used for this purpose (21,22). 

Other Borohydrides. Potassium borohydride was formerly used in color reversal development of photographic film and was preferred over sodium borohydride because of its much lower hygroscopicity. Because other borohydrides are made from sodium borohydride, they are correspondingly more expensive. Generally their reducing properties are not sufficiently different to warrant the added cost. Zinc borohydride [17611-70-0] Zn(BH 2> however, has found many appHcations in stereoselective reductions. It is less basic than NaBH, but is not commercially available owing to poor thermal stabihty. It is usually prepared on site in an ether solvent. Zinc borohydride was initially appHed to stereoselective ketone reductions, especially in prostaglandin syntheses (36), and later to aldehydes, acid haHdes, and esters (37). 

Industrial Synthetic Improvements. One significant modification of the Stembach process is the result of work by Sumitomo chemists in 1975, in which the optical resolution—reduction sequence is replaced with a more efficient asymmetric conversion of the meso-cyc. 02Lcid (13) to the optically pure i7-lactone (17) (Fig. 3) (25). The cycloacid is reacted with the optically active dihydroxyamine [2964-48-9] (23) to quantitatively yield the chiral imide [85317-83-5] (24). Diastereoselective reduction of the pro-R-carbonyl using sodium borohydride affords the optically pure hydroxyamide [85317-84-6] (25) after recrystaUization. Acid hydrolysis of the amide then yields the desired i7-lactone (17). A similar approach uses chiral alcohols to form diastereomic half-esters stereoselectivity. These are reduced and direedy converted to i7-lactone (26). In both approaches, the desired diastereomeric half-amide or half-ester is formed in excess, thus avoiding the cosdy resolution step required in the Stembach synthesis. 

Methyl borate is beheved to be the boric acid ester produced in the largest quantity, approximately 8600 metric tons per year (28). Most methyl borate is produced by Morton International and used captively to manufacture sodium borohydride [16940-66-2]. Methyl borate production was studied in detail during the 1950s and 1960s when this compound was proposed as a key intermediate for production of high energy fuels. Methyl borate is sold as either the pure compound or as the methanol azeotrope that consists of approximately a 1 1 molar ratio of methanol to methyl borate. 

Reduction of the imine with sodium borohydride leads to an intermediate amino-ester that cyclizes spontaneously to the <5-lactam function. Solvolysis of the acetyl group with methoxide followed by acylation of the hydroxyl group thus liberated with trimethoxybenzoyl chloride leads to 38. Bischler-Napieralski cyclodehydration (phosphorus oxychloride) effects closure of the remaining ring. Reduction of the imine thus formed with sodium borohydride gives 39. This, it should be noted, leads to the... 

N-Succinimido4-phenoxy-5-sulfamylbenzoic acid methyl ester Sodium borohydride Sodium hydroxide... 

Intermediate 10 must now be molded into a form suitable for coupling with the anion derived from dithiane 9. To this end, a che-moselective reduction of the benzyl ester grouping in 10 with excess sodium borohydride in methanol takes place smoothly and provides primary alcohol 14. Treatment of 14 with methanesulfonyl chloride and triethylamine affords a primary mesylate which is subsequently converted into iodide 15 with sodium iodide in acetone. Exposure of 15 to tert-butyldimethylsilyl chloride and triethylamine accomplishes protection of the /Mactam nitrogen and leads to the formation of 8. Starting from L-aspartic acid (12), the overall yield of 8 is approximately 50%, and it is noteworthy that this reaction sequence can be performed on a molar scale. 

The final stages of the successful drive towards amphotericin B (1) are presented in Scheme 19. Thus, compound 9 is obtained stereoselectively by sodium borohydride reduction of heptaenone 6a as previously described. The formation of the desired glycosida-tion product 81 could be achieved in dilute hexane solution in the presence of a catalytic amount PPTS. The by-product ortho ester 85 was also obtained in approximately an equimolar amount. Deacetylation of 81 at C-2, followed sequentially by oxidation and reduction leads, stereoselectively, to the desired hydroxy compound 83 via ketone 82. The configuration of each of the two hydroxylbearing stereocenters generated by reduction of carbonyls as shown in Scheme 19 (6—>9 and 82->83) were confirmed by conversion of 83 to amphotericin B derivative 5 and comparison with an... 

The synthesis of the E-ring intermediate 20 commences with the methyl ester of enantiomerically pure L-serine hydrochloride (22) (see Scheme 9). The primary amino group of 22 can be alkylated in a straightforward manner by treatment with acetaldehyde, followed by reduction of the intermediate imine with sodium borohydride (see 22 —> 51). The primary hydroxyl and secondary amino groups in 51 are affixed to adjacent carbon atoms. By virtue of this close spatial relationship, it seemed reasonable to expect that the simultaneous protection of these two functions in the form of an oxazolidi-none ring could be achieved. Indeed, treatment of 51 with l,l -car-bonyldiimidazole in refluxing acetonitrile, followed by partial reduction of the methoxycarbonyl function with one equivalent of Dibal-H provides oxazolidinone aldehyde 52. 

The procedures for the reactions of the boronate tartrate esters and tartramides are similar71 13. The reactions of tartramides are much slower (typically 2 4 days) due to their poor solubility in toluene at —78 °C, and these reactions were therefore quenched at —78 °C by the addition of excess sodium borohydride in ethanol to consume any unreacted aldehyde before the reactions were allowed to warm above — 78°C73. 

Ueno and coworkers49 have developed a procedure for the synthesis of chiral sulfinic acids. Treatment of (R)-( + )-23 with disulfide 24 and tributylphosphine in THF gave (S)-( — )-25. Compound 25 was oxidized with potassium permanganate to the sulfone, which was then reduced to the sulfinic acid, (S)-( — )-26, by treatment with sodium borohydride. Conversion of 26 or an analog to an ester would lead to diastereomers. If these epimers could be separated, then they would offer a path to homochiral sulfoxides with stereogenic carbon and sulfur atoms. 

Lewis acid strength and hardness of the lithium cation. Both LiBH4 and Ca(BH4)2 are more reactive than sodium borohydride. This enhanced reactivity is due to the greater Lewis acid strength of Li+ and Ca2+, compared with Na+. Both of these reagents can reduce esters and lactones efficiently. 

The first conversion of protoberberines to phthalideisoquinoline alkaloids was achieved by Moniot and Shamma (88,89). 8-Methoxyberberinephenol-betaine (131), derived from berberine (15) (Section III,B,2), is an attractive compound having a carboxyl group masked as an imino ether in ring B. The masking was uncovered by hydration with water-saturated ether to furnish dehydronorhydrastine methyl ester (367) (Scheme 65). On N-methylation (68%) and subsequent sodium borohydride reduction (90%), 367 provided (+ )-/ -hydrastine (368) and ( )-a-hydrastine (369) in a 2 1 ratio. Compound 367 was converted to dehydrohydrastine (370), which also afforded 368 and 369 by catalytic hydrogenation. 

Keto acids can be dehydrated to enol lactones (Section III,A,1). They may also undergo esterification with alcohols e.g., /V-methylhydrasteine (104) in methanol at room temperature gave the expected keto ester 126 (R + R = CH2, R1 = CH3) (5,87). Sodium borohydride reduction of keto acid 104 supplies the saturated y-lactone 132 identical with that obtained from enol lactone 98 (5). 

The structure of narlumidine (119) was established by Dasgupta et al. (117,119) on the basis of spectral data, particularly by comparison with spectra of bicucullinine (108), and also on chemical grounds. On hydrolysis followed by oxidation-methylation, narlumidine (119) was converted to ester 147, which was also obtained from 108 by N.O-methylation. Sodium borohydride reduction gave lactone 145, identical to the lactone obtained from 108. 

---