Hydroxy amides Sodium borohydride

All that remains before the final destination is reached is the introduction of the C-l3 oxygen and attachment of the side chain. A simple oxidation of compound 4 with pyridinium chlorochro-mate (PCC) provides the desired A-ring enone in 75 % yield via a regioselective allylic oxidation. Sodium borohydride reduction of the latter compound then leads to the desired 13a-hydroxy compound 2 (83% yield). Sequential treatment of 2 with sodium bis(trimethylsilyl)amide and /(-lactam 3 according to the Ojima-Holton method36 provides taxol bis(triethylsilyl ether) (86 % yield, based on 89% conversion) from which taxol (1) can be liberated, in 80 % yield, by exposure to HF pyridine in THF at room temperature. Thus the total synthesis of (-)-taxol (1) was accomplished. 

A series of N-substituted narceine amides (Section III,D,1) was prepared from 101 under the action of primary amines (100). Acid-catalyzed dehydration transformed these amides to corresponding imides (ene lactams) of the ( )-narceine imide (117) type (100). Similar transformations were performed in the hydrastine series (101). JV-Methylhydrastine (98) when treated with dilute ammonium hydroxide gave hydroxy lactam 127, which was dehydrated to (Z)-fumaridine (113) (5). Sodium borohydride was able to reduce the stilbene double bond in 98 to produce saturated lactone 132 (5). 

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. 

The synthesis of 3-hydroxy-2-methyl esters and amides in a stereoselective manner is a challenge which needs to be met due to the prevalence of these moieties in natural products201. This has been accomplished by using sodium borohydride, catalyzed by manganese(II) chloride or by tetrabutylammonium borohydride (equation 52)202,203. 

Amidals 1 were prepared by the reaction of secondary allylic alcohols with benzyl hydroxy-methylcarbamate in dichloromethane using 4-methylbenzenesulfonic acid as a catalyst. The cyclization proceeded by treating 1 with mercury(II) acetate (1.25-2.0 equiv) in acetonitrile at 20 °C for 12 hours, followed by addition of sodium acetate and sodium borohydride to give the corresponding oxazolidine 2 in 60-90% yield158. 

Fragmentations of heterocycles have played an important role in the preparation of amide derivatives. Moderate to good yields of a-hydroxy-amides were obtained on reaction of a-hydroxy-acid aceto-nides with primary amines.N-Alkyl-2-methyl-2-oxazolinium salts (obtained by mixing alkyl halides and 2-methyl-2-oxazoline in dichloromethane) were found to react with sodium benzeneselenolate to yield -(2-phenylselenoethyl)-t -alkylacetamides, which after oxidation to ] -vinyl analogues with sodium metaperiodate in methanol, gave secondary amides on sequential treatment with mercuric acetate in aqueous tetrahydrofuran and sodium borohydride/3M... 

An unusual effect of a mixed solvent on the asymmetric reduction by sodium borohydride of chiral a-keto-amides that are derived from proline has been observed which may have important consequences for the synthesis of chiral hydroxy-acids. ... 

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