Hydroboration-oxidation enamines

A biomimetic synthesis of benzo[c]phenanthridine alkaloids from a protoberberine via the equivalent of a hypothetical aldehyde enamine intermediate has been developed (130,131). The enamide 230 derived from berberine (15) was subjected to hydroboration-oxidation to give alcohol 231, oxidation of which with pyridinium chlorochromate afforded directly oxyche-lerythrine (232) instead of the expected aldehyde enamide 233. However, the formation of oxychelerythrine can be rationalized in terms of the intermediacy of 233 as shown in Scheme 41. An alternative and more efficient... 

The oxidation of hexahydroindolo[2,3-a]quinolizin (574) with benzoyl peroxide, followed by reduction and removal of the benzoyl group, gave the cis alcohol (575), while hydroboration-oxidation of the same enamine (574) yielded... 

Asymmetric hydroboration of enamines with chiral diboranes, followed by oxidation with hydrogen peroxide, in aqueous sodium hydroxide, gives /1-amino alcohols in good yields and high ee (equation 29)153. The products of this reaction are useful in medicinal applications and as synthons for further synthetic elaboration. 

Hydroboration-oxidation of enamines has been reported by Borowitz and Williams171 to furnish the corresponding trans amino alcohols (Scheme 119). 

Enamines of unsaturated aldehydes can be converted into the corresponding dienes for example, citronellal, a chiral aldehyde, gives the chiral non-conjugated diene, /f-citronellene, in 92% enantiomeric excess - (Scheme 172). The combination of the Lewis hydroboration procedure with the thallium acetate acetoxylation of enamines provides a means of converting enamines into acetoxycycloalkenes (Scheme 173). The hydroboration oxidation of enamines to give -aminoalcohols was first reported by Borowitz and Williams . Cw-l,2-addition of BH3 occurs, to give the trans-ji-ammocy-... 

This general procedure for the synthesis of alkenes from the enamines, when applied to the acyclic enamines derived from the acyclic ketones by modification of hydroboration-elimination procedure, permits a facile, diastereospecific conversion to either (Z)- or (E)-alkene at will (A) The hydroboration of enamine with 9-BBN, followed by treatment with methanol gives (Z)-alkenes of 99% isomeric purity. (B) The hydroboration of the same enamine with borane-methylsulfide, followed by methanolysis and oxidation with neutral hydrogen peroxide gives ( )-alkenes of 99% isomeric purity (Scheme 24.2) [13a]. 

HCN, 193, 442 de-conjugation, 159 dehydrogenation, 189 enamine formation, 185-186 enolisation, 156 ei seq. epoxidation, 18, 201, 442 formation, 109, 189, 248, 337 hydroboration. So Mannich reaction (aminometh-ylation), 172 methylation, 168-171 methylene addition, 202 oxidation, Baeyer-VUliger, 349, 445... 

The structure of (24) was established by the chemical correlation shown in Scheme 3. Reduction of (24) with NaBH4 gave a mixture of (26), O-to-N acyl migration product, and (27) the latter was methylated to (29) which was identical with the product formed from the enamine (28) by oxidative hydroboration. 

The ketone 629 has been isolated from peony flowers. It had already been synthesized several times for example, by hydroboration of the enamine 630 of the isomeric ketone 627, then Cope elimination of the iV-oxide 631 of the amino alcohol. Chromyl acetate oxidation of 1,8-cineole (553) led first to 629 further oxidation gave diketones. Aspergillus niger also gave some 629, although the main products were the corresponding alcohols. ... 

Turning now to the synthesis of isopavines, a required intermediate for this purpose is again an appropriately substituted 1,2-dihydro-A -methylbenzyl-isoquinoline. Hydroboration of the enamine system and oxidative work-up induce formation of a 4-hydroxybenzylisoquinoline which can be cyclized in acid to the isopavine skeleton. A recent example of such a synthesis leads to the new isopavine thalidine ... 

Dehydroprotoberberinium salts may be used as intermediates for the introduction of substituents at the C-5 position of tetrahydroprotoberberine bases. Two-step reduction of dehydronorcoralydine leads to the enamine 51 which can be C-acylated as in 52, or hydroborated and oxidized to give a separable mixture of diastereomeric C-5 hydroxylated tetrahydroprotoberbines ... 

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