Imides regioselective reductions

Tamura and coworkers have reported a fairly general route to several of the grandisines and analogs in which the chiral imide (—)-877, itself prepared by a known route from L-mahc acid, ° served as the precursor (Scheme 109). Regioselective reduction, ethanolysis, and cross-metathesis... 

Maleimides (pyrrole-2,5-diones) can be converted into 3-pyrrolin-2-ones and 5-hydroxy-3-pyrrohn-2-ones by complete or partial reduction of one of the imide carbonyls, respectively. In the case of unsymmetrical substrates, the reaction requires a regioselective reduction of one of the two carbonyls there has been success in this area although some substrates prove to be problematic (1994TL9135,1999TA4469). Nucleophihc additions to maleimides by carbon-based nucleophilics also provide access to 3-pyrrolin-2-ones. 

More symmetrical imides may still be regioselectively reduced. In the case of geminally disub-stituted succinimidcs the stcrically more hindered carbonyl function is preferentially reduced with sodium borohydride. The regioselectivity ranges from 79 21 for the dimethyl derivative to > 95 5 for the diphenyl derivative29. For monosubstituted succinimides the selectivity of the reduction is low29, unless the substituent is an acetoxy group35-36. 

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. 

Diastereoselective aldol reactions The boryl enolates of chiral crotonate imides (1) and (2) react with aldehydes to form adducts (3) and (4), respectively, with high diastereoselectivity and complete a-regioselectivity. The method of choice for reductive cleavage of the adducts is formulated for 3 hydrolysis can also be effected with LiOH and H202. 

Trifluoropropcnc itself reacts regioselectively with various nitrile oxides, even nonaromatic nitrile oxides. The latter arc prepared in one step from oximes and A -chlorosuccin-imide, or in a two-step sequence with isolation of the hydroximoyl chlorides. Cycloadducts, obtained at room temperature in the presence of triethylamine, are then converted into trilluoro- 8-hydroxy ketones 9 by reductive cleavage. The reaction with a dipole substituted by a group derived from L-phcnylalanine allows the preparation of chiral ketones. ... 

Two new syntheses of racemic mesembrine have been described. In the first, outlined in Scheme 1, an improved synthesis of the penultimate 2-pyrroline (8) was achieved annelation of this afforded ( )-mesembrine (9). The second (Scheme 2) incorporates a regioselective borohydride imide reduction. Investigations on the biosynthesis of mesembrine alkaloids have revealed that a stereospecific protonation occurs at C-7 [see formula (9)] as one of the late stages. ... 

Finally, the regioselection in metal-hydride reduction of unsymmetrically substituted acyclic diesters is not understood [176] here, as well as in the reactions of cyclic anhydrides and imides, the effect of steric hindrance appears to play a minor role. 

In spite of the low regioselectivity observed in Eq. (3), we were able to develop a number of pyrrolizidine alkaloid syntheses through rational modifications of the cyclization substrate. Our first examples of pyrrolizidine alkaloid syntheses are outlined in Scheme 1 [7]. Imide 7 was prepared from succinimide and 3-butyn-l-ol in 6 steps. Reduction of 7 followed by hydroxy-thiophenoxy exchange gave cyclization substrate 8. Treatment of 8 with TBTH gave a 71% isolated yield of pyrrolizi-dinone 9, which was converted to isoretronecanol in 4 steps. The radical cyclization step also gave small amounts of the C] isomer of 9, reduction product 10 (5%), and... 

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. 

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. 

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