Hydroxy-lactams => imides

Dicarbonsaure-imide ergeben als cyclische sekundare Carbonsaure-amide mit Hydri-den die verschiedensten Reduktionsprodukte, z. B. Hydroxy-lactame, Lactame, cyclische Amine, a>-Hydroxy-carbonsaureamide und a>-Amino-alkohole4. 

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). 

The hydroxy lactams are postulated to be intermediates in transformations of enol lactones to ene lactams. This hypothesis was proved by synthesis. For example, treatment of N-methylhydrastine (98) with dilute ammonium hydroxide resulted in hydroxy lactam 148, which by the action of hydrochloric acid underwent dehydration to produce fumaridine (113) (5). Similarily, fumschleicherine (120) in reaction with trifluoroacetic acid gave fumaramine (111) 121). Narceine amide (149) was prepared from (Z)-narceine enol lactone (101) in likewise fashion 100,122) and dehydrated to narceine imide (116). A large number of N-alkylated narceine amides was synthesized from (Z)-narceine enol lactone (101) and primary amines by Czech investigators for... 

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. 

Reduction of imides.1 The N-imidotryptamine (1) is reduced selectively by NaBH4 CoCl2 (5 1 equivalents) to the hydroxy lactam 2 in 95% yield. The product is converted in quantitative yield to the /l-curbolinc 3 by treatment with cone. I IC I ill. 31). ... 

Mechanistic studies41"43 by Dixon and Jones excluded the possibility of dimeric catalytic species because a linear dependence was observed between the catalyst s enantiopurity and the reaction s enantioselectivity.43 The test reaction was the desymmetrization of meso-imide 22 using chiral oxazaborolidine catalysts. The sense of the enantioselectivity of the reduction was established by conversion of hydroxy lactam 23 to the known ethoxy lactam 24 (Scheme 17.6). 

Reduction of one carbonyl group to a hydroxy group in cyclic imides has been achieved to afford useful synthetic intermediates. The reaction (Scheme 17) is analogous to that shown for lactams (Scheme 16). Thus, reduction of cyclic imides (36) with NaBH4 in acidulated water has given good yields of the hydroxy lactam (37).Many similar examples by the same research group have appeared.With so-... 

Cyclic imide reduction. The reagent reduces imides to give hydroxy lactams in a regioselective manner, which is different from LiBHEtj. The complementary is very useful in synthesis. 

To complete the total S3mthesis of ent-staurosporine (2), a two-step deprotection strategy (hydrogenation followed by aminal hydrolysis) delivered 64 from 63 in high yield (Scheme 8). Danishefsky et al. preferred to clarify the monosaccharide domain prior to reducing the maleimide function [45], The most efficient method involved reduction of the imide group with sodium borohydride to provide a mixture of hydroxy lactams. Further reduction... 

The 2b-catalyzed reduction of j or 8-keto esters provided the corresponding hydroxy esters with high enantioselectivity (Scheme 11.9) [5b], while the reduction of a-keto esters was less effective [6b, 44b, 59]. Desymmetrization of meso-imides 31 via stereoselective reduction is one of the most powerful transformations to provide products with three new chiral centers. Such transformations with good enantioselectivities were achieved by OABs-catalyzed reductions (Scheme 11.10) [60-62], The hydroxy lactams 32 obtained were easily converted into ethoxy lactams 33 by acidic ethanoly-sis, and were transformed into chiral lactones 34 by sodium borohydride reduction. 

Tlie infrared spectra revealed the dominance of the 2-oxo (153) and 5-0X0 (157) structures (amide or lactam tautomers) over the 2-hydroxy (154) and the 5-hydroxy (192) structures (imidic acid or lactim tautomers)... 

In 1999, this methodology was applied to the synthesis of unnatural biologically active ( + )-5-epi-nojirimycin-5-lactam, a potent and selective glycosidase inhibitor.The key step of this synthesis was the asymmetric reduction of a cyclic triacetyloxy meso imide under the same conditions to those described above, which resulted in the formation of the corresponding hydroxy 5-lactam in good yield and enantioselectivity of 85% ee (Scheme 10.59). 

In general, aldehydes, ketones, acids, esters, and acid chlorides are all reduced to the corresponding alcohols hy this reagent. Alkyl halides are unreactive towards DIBAL. Amides are reduced to amines, while nitriles afford aldehydes upon hydrolysis of an intermediate imine. Isocyanates are also reduced to the corresponding imines. Nitro compounds are reduced to hydroxy-lamines. Disulfides are reduced to thiols, while sulfides, suhbnes, and sulfonic acids are unreactive in toluene at 0°C. Tosylates are converted quantitatively to the corresponding alkanes. Cyclic imides can be reduced to carbinol lactams. 

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