Reduction of imides

Some other typical examples of regiosclcctivc reductions of imides with sodium borohydride in ethanol are42 ... 

Wunberg, J.B.P.A. Speckamp, W.N. (1978) New Total Synthesis of dl-Physostigmine (dl-Eserine) Via Regioselective NaBH4-reduction of Imides. Tetrahedron, 34, 2399-2404. 

A-Acyliminium ions are usually prepared in situ in the presence of a potential nucleophile. There are several ways of generating acyliminium ions. Cyclic examples can be generated by partial reduction of imides.204... 

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). ... 

Vertaline (61) was synthesized through two routes that involve an W-acylimin-ium ion cyclization (20) and an intermolecular [3 + 2] cycloaddition (21,22) as the key steps, respectively. Model studies (20, 24) for assembling the quinolizi-dine moiety by the W-acyliminium ion cyclization are shown in Scheme 7. The benzyl alcohol 65 was converted to glutarimide 66 by the Mitsunobu procedure in 55% yield. Reduction of imide 66 with diisobutylaluminum hydride afforded 67, which was subjected to V-acyliminium cyclization to give the lactam 68 in 40% overall yield from 66. Lactam 68 possesses the correct stereochemistry at all chiral centers required for vertaline (61). 

The preparation of acyliminium ions is not restricted to aldehyde or ketone derivatives as starting materials, but can also use the more highly oxidized carboxylic acid amides as precursors, e.g. reduction of imides (66) affords (67 Scheme 33). For constitutionally unsymmetrical imides, regiocontrol can be achieved in many cases by the choice of the appropriate hydride-transfer reagent. ... 

N-(l-Alkoxyalkyl)-aniides or -carbamates (2 X = OR), most frequently used as stable precursors for A -acyliminium ions, are usually prepared by one of the following routes (equations 7-13). For five- or six-membered cyclic cases a simple acid-catalyzed solvolysis of the hydroxy compound provides the alk-oxy derivative (equation 7). A silicon-assisted approach involves the TMSOTf-catalyzed reaction of bis(trimethylsilyl)formamide with aldehydes (equation 8). /V-(l-Trimethylsilyloxyalkyl)formamides are thus formed in good yields, which on TMSOTf-catalyzed solvolysis lead to the /V-( 1-alkoxyalkyl)form-amides. A third method is based on the NaBH4 reduction of imidates (equation 9), and has proved useful for a total synthesis of the insect poison pederine. Addition of reactive acid derivatives to imines constitutes another method (equations 10 and 11). Acylation with acid chlorides followed by treatment with ethanol in the presence of base leads to N-(l-alkoxyalkyl)amides. A one-step protocol using diethyl dicarbonate provides the corresponding carbamates. 2... 

A second-generation process ronte was developed that improves upon the initial process route (Scheme 6). - - In this simplified process approach, the molecular symmetry of the starting caronic anhydride was maintained to the latest stage possible. Caronic anhydride (30) was initially converted directly to imide 40 by heating with either ammonium hydroxide or formamide with DMAP under Dean-Stark conditions. In an alternative two-step protocol, heating of 30 with benzyl amine produced an intermediate benzyl imide, which was deprotected to 40 under catalytic hydrogenation conditions. Reduction of imide 40 with lithium aluminum hydride afforded 41, which was desymmetrized under oxidative conditions to produce racemic imine 42. Diastereoselective cyanation favored trans-43, which underwent methanolysis under Pinner conditions. Finally, classical resolution by crystallization with D-DTTA afforded 24 as the D-DTTA salt with >95% ee. 

Danishefsky formulated a strategy to staurosporine [41], in which epoxidation of glycal (-)-98 with maleimide 97 resulted in one of the indole N-glycosidic linkages to form 99. Treatment of olefin 99 using Barton deoxygenation, iodine and f-BuOK followed by radical dehalogenation provided the pyranosylated indolocarbazole 101 with 64% yield. Deprotection and methylation followed as shown in Scheme 14 (i.e., 101—102), after which reduction of imide 102 led to a 1 1 mixture of 1 and la. 

Reduction of imide to dinitrogen compiex and ammonia imide is sacrificial source of protons... 

The reduction of imidization process activation energy at increase was found out - from 66 up to 51 kj/mole within the range W= 0-7 mass% [2], Earlier the authors [28] offered the following dependence of on in case of polyary late thermooxidative degradation ... 

J. B. P. A. Wijnberg and W. N. Speckamp. Total synthesis of d/-mesembrine, d/-dihydro-maritidine and d/-epidihydromaritidine via regioselective NaBH4/H+ reduction of imides. Tetrahedron, 1978,34,2579. 

Key steps in two formal syntheses of racemic 8a-ep -dendroprimine rac-787) are shown in Scheme 103. Hsu et al. employed the stepwise [3 + 3] cycloaddition of the dianion of N-benzyl-2-(p-toluenesulfonyl)acetamide 797 to methyl crotonate (798) to yield the 3-sulfonylglutarimide 799, the iw 5-stereochemistry of which was established by X-ray analysis. Replacement of the JV-benzyl substituent by a 3-chloropropyl chain was followed by regiospecific reduction of imide 800 with sodium borohydride... 

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