Nitriles regioselective reductions

Oxo-2-alkenylphosphonates (259) have been prepared from alkenylphos-phonates by cycloaddition reactions with nitrile oxides, reduction and deprotection (Scheme 42). The approach offers a new method for regioselective y-acylation of allylicphosphonates. 

The bonding in R2B(p-H)2BR2 can be described in a similar manner to that in B2H6 (see Section 4.7). An important member of this family is 18.6, commonly known as 9-BBN, which is used for the regioselective reduction of ketones, aldehydes, alkynes and nitriles. 

The application of microwaves to the cycloaddition reactions of allyl alcohols 180 with nitrile oxides not only achieved a substantial reduction of the reaction time and an improvement of the adduct yields, but also altered the regioselectivity of the cycloaddition in favor of the nonhydrogen bond-directed cycloadduct 182 (Scheme 9.55) [105]. 

The nucleophiles that are used for synthetic purposes include water, alcohols, carboxylate ions, hydroperoxides, amines, and nitriles. After the addition step is complete, the mercury is usually reductively removed by sodium borohydride. The net result is the addition of hydrogen and the nucleophile to the alkene. The regioselectivity is excellent and is in the same sense as is observed for proton-initiated additions.16 Scheme 4.1 includes examples of these reactions. Electrophilic attack by mercuric ion can affect cyclization by intramolecular capture of a nucleophilic functional group, as illustrated by entries 9-11. Inclusion of triethylboron in the reduction has been found to improve yields (entry 9).17... 

XLIV) centers about elaboration of hydroxymethylene ketone (574) into the tricyclic diketone (578). Alkylation of keto nitrile 575 proceeds exclusively cis to the angular methyl groups as does the subsequent reductive methylation. These authors were not able to achieve aldol cycUzation of keto aldehyde 576 and consequently proceeded to enol lactone 577 The addition of a methyl group to 578 could be achieved regioselectively. Subsequently dehydration gave 579 and its endocyclic isomer which were separated chromatographically. 

A rational extension of ortho-tolyl benzamide metalation [68], part of the broadly encompassing lateral metalation protocol [69] that can be DoM-connected, is the DreM equivalent, 154 —> 155 (Scheme 41), which provides a general regioselective route to 9-phenanthrols (156, 157, 158) [70] and may be extended to diaryl nitriles, hydroxylamine ethers, and hy-drazones 160, which provide the corresponding 9-amino derivatives 161 of similar generality 162-165 (Scheme 42), as may also be applied in natural product synthesis [71]. Further opportunities for DoM-cross-coupling and reduction/oxidation chemistry (159) have also been demonstrated [70a]. 

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. ... 

The active nickel catalyst contains one bidentate phos-phinite ligand and the overall mechanism of the reaction is believed to be similar to butadiene hydrocyanation except that the final reductive elimination step is irreversible under the conditions of the reaction. jr-Allyl intermediates (7) are believed to play an important role in the exclusive formation of the branched nitrile product observed. Formation of the C-CN bond in the final reductive ehmination from the r-allyl intermediate occurs at C(2) and not C(4), because the aromaticity of the naphthalene ring is preserved only when the bond forms with C(2). A a-alkyl complex see a-Bond) with the Ni bound to C(l), which could give the linear (anti-Markovnikov) nitrile product, does not contribute because of the much greater stability of intermediate (7), accounting for the high regioselectivity observed. 

The features of Red-Al are the following It easily reduces halogenated derivatives even if acetylenic (Section 2.1) tertiary amides lead to aldehydes (Section 3.2.8) and propargylic alcohols and amines are reduced to corresponding allylic alcohols and amines (Section 4.1). Epoxides remain intact unless they carry an alcohol functional group at the a position The reduction is then regioselective (Section 2.3). Aromatic nitriles are reduced, but aliphatic nitriles are not affected (Section 4.3). 

Metallation of a-substituted a,P-unsaturated nitriles followed by introduction of dry oxygen gas results in the regioselective trapping of the delocalized anion at the a carbon to produce the hydroperoxide. Reduction with aqueous NujSO, and exposure of the cyanohydrin to NaOH affords the p.y-unsaturated ketones in good yields (Scheme 6.57).- 5 ... 

---