Lactones reduction with sodium borohydride

Addition of methyllithium to the lactone 1219, followed by reduction with sodium borohydride in refluxing ethanol, afforded, almost quantitatively, ellipticine (228). Reaction of the compound 1219 with the lithio derivative of formaldehyde diethylmercaptal, and reduction with sodium borohydride in refluxing ethanol, led to the mercaptal 1221. Cleavage of the mercaptal 1221 with bis(trifluoroacetoxy) iodobenzene [Phl(OCOCF3)2] in aqueous acetonitrile gave the 11-formyl derivative, which was reduced with sodium cyanoborohydride (NaBHsCN) to 12-hydroxyellipticine (232) (710,711) (Scheme 5.202). The same group also reported the synthesis of further pyiido[4,3-fc]carbazole derivatives by condensation of 2-substituted indoles with 3-acetylpyridine (712). 

Methylcryptaustoline iodide (14) was synthesized from phenylacetic acid 47 by Elliott (39) as shown in Scheme 7. Nitration of 47 to the 6-nitro compound 48 and reduction with sodium borohydride afforded lactone 49. Reduction of the aromatic nitro group with iron powder in acetic acid gave ami-nolactone 50, which was converted to tetracyclic lactam 51 with trifluoroacetic acid in dichloromethane. Reduction of the lactam by a borane-THF complex followed by treatment with methyl iodide afforded ( )-0-methylcryptaustoline iodide (14). 

A different approach to enantiotopic group differentiation in bicyclic anhydrides consists of their two-step conversion, first with (/ )-2-amino-2-phcnylethanol to chiral imides 3, then by diastereoselective reduction with sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al) to the corresponding chiral hydroxy lactames 4, which may be converted to the corresponding lactones 5 via reduction with sodium borohydride and cyclization of the hydroxyalkyl amides 101 The overall yield is good and the enantioselectivity ranges from moderate to good. Absolute configurations of the lactones are based on chemical correlation. 

L-Mannitol does not occur naturally but is obtained by the reduction of L-mannose or L-mannonic acid lactone (80). It can be synthesized from the relatively abundant L-arabinose through the L-mannose and L-glucose cyanohydrins, conversion to the phenylhydrazines which are separated, liberation of L-mannose, and reduction with sodium borohydride (81). Another synthesis is from L-inositol (obtained from its monomethyl ether, quebrachitol) through the diacetonate, periodate oxidation to the blocked dialdehyde, reduction, and removal of the acetone blocking groups (82). 

An alternative route to the erythro.threo diastereoisomeric mixture of alcohols results from the acylation of the alkyldiphenylphosphine oxide with an ester or lactone to yield the /J-ketophosphine oxide, followed by reduction with sodium borohydride. This reduction shows f/ireo-selectivity, so that, following separation of the diastereoisomers, a preparatively useful route to ( )-alkenes is achieved. 

We also found that ester functionality was compatible with this reduction sequence. Thus, treatment of the ester-lactone 81 with sodium borohydride and boron trifluoride etherate provided the tetrahydropyran 123 in 55% purified yield. Upon reaction with sodium hydroxide, 81 underwent simple ester hydrolysis to furnish the carboxylic acid 127 (see Table 3). 

The 7-hydroxy telluride 161 is prepared by hydrotelluration of methyl vinyl ketone, followed by in situ reduction with sodium borohydride.154 Treatment of 161 with 2 equiv. of nBuLi, followed by capture of the dianion 162 with electrophiles, gives the corresponding alcohols 163.252 Dianions like 162 can be transmetallated with CeCf , leading to organometallics of the type 164, which on reaction with lactones give spiroketals (Scheme 94).253... 

Hydrastine has been prepared by the hydrogenolysis of the 1-phenyl-l/f-5-tetrazolyl ether of (—)-a-narcotoline,154 and in the racemic form by the reductive cyclization of the quaternary salt of the keto-acid (53) that is obtained from oxidoberberine (51) as described above.133 The lactone (80), prepared by the dye-sensitized photo-oxidation of oxidonorcoralyne followed by reduction with sodium borohydride and from 6 -acetylpapaveraldine by oxidation with hypo-bromite followed by reduction, has been TV-methylated and reduced with sodium borohydride to an isomer of cordrastine.133 Cordrastine itself has been synthesized by the electrolytic reduction of a mixture of the iminium salt (81) and bromomeconine (82), a process that has been shown to be of general applicability to the synthesis of alkaloids of this group.155... 

Mitsunobu reaction as well as by mesylation and subsequent base treatment failed, the secondary alcohol was inverted by oxidation with pyridinium dichromate and successive reduction with sodium borohydride. The inverted alcohol 454 was protected as an acetate and the acetonide was removed by acid treatment to enable conformational flexibility. Persilylation of triol 455 was succeeded by acetate cleavage with guanidine. Alcohol 456 was deprotonated to assist lactonization. Mild and short treatment with aqueous hydrogen fluoride allowed selective cleavage of the secondary silyl ether. Dehydration of the alcohol 457 was achieved by Tshugaejf vesLCtion. The final steps toward corianin (21) were deprotection of the tertiary alcohols of 458 and epoxidation with peracid. This alternative corianin synthesis needed 34 steps in 0.13% overall yield. 

The cyclohexanone (S3), an intermediate for the synthesis of thromboxane antagonists, has been prepared by a combination of phosphine oxide- and phosphonium ylide-based olefinations.30 Reaction of the lactone (50) with methoxymethyldiphenylphosphine oxide anion gave a poorly characterized adduct (presumably (51)) which on reduction with sodium borohydride, followed by treatment with sodium hydride gave the vinyl ether (52) in 80% overall yield from (SO) (Scheme 8). Further modification gave the required cyclohexanone (53). 

Treatment of 3-(l-benzyloxymethylcyclopropyl)propanoic acid with various mercury(II) salts such as nitrate, trifluoroacetate and perchlorate gave the lactones 25A and 25B in 35-86% yield after aqueous potassium bromide workup. A number of related cyclopropanecarboxylic esters were reacted in the same fashion to give bromomercurio-substituted lactones 26 and 27/28 from which the mercury was removed by reduction with sodium borohydride. ... 

S-Lactones. 6-Lactones can be prepared conveniently from cyclohexenones by ozonolysis at -60 followed by reduction with sodium borohydride at 0. Yields are only moderate (25-60%). ... 

Since segment A (4) is a somewhat large molecule, it was subdivided into Aj (5) and A2 (6). The 2-acetoxyglucal (7) was first converted to 10 via 8 and 9. Stereoselective oxymercuration of the double bond in 10 and subsequent reduction with sodium borohydride gave the diol (11). After protection of the diol, the acetal was cleaved and oxidized to give the lactone (segment A 5) [5a, c]. 

To construct tricycHc compound 275, they first employed sodium boro-hydride to reduce the keto group to furnish alcohol 273. The terminal olefin was then converted to an alcohol via a two-step protocol employing oxidation with osmium tetroxide and sodium periodate followed by reduction with sodium borohydride to furnish diol 274, which underwent acid mediated lactonization. Dess—Martin oxidation of the remaining secondary alcohol then led to the desired tricyclic lactone 275. 

The introduction of acid catalysis effected by the acid form of a suitable ion-exchange resin, has also led to the synthesis of the anomeric methyl glycosides of D-glucurono-7-lactone (10). As these glycosides were known to be furanoid (11), reduction of the lactone (12) with sodium borohydride (13) yielded the anomeric forms of methyl D-glucofuranoside. 

---