Conjugate cyanation

Stereospecific conjugate cyanation. By adjusting the reaction conditions, Kelly et al. were able to convert the octalone (1) into either the cis-cyano-decalone (2) or the trans-isomer (3). 

Scheme 18 Proposed catalytic cycle of enantioselective conjugate cyanation promoted by a strontium complex...

Motomu Kanai and Masakatsu Shibasaki of the University of Tokyo devised (J. ArtL Chem. Soc. 2008,130, 6072) a chiral Gd catalyst that mediated the conjugate cyanation of enones such as 6 with high ee. Eric N. Jacobsen of Harvard University prepared Angew. Chem. Int. Ed. 2008,47,1762) a dimeric A1 salen catalyst that showed improved activity over the monomeric catalysts. Even congested imides such as 8 could be cyanated efficiently, delivering alkylated quaternary stereogenic centers. 

Figure 3-8. Chiral catalysts for enantioselective conjugate cyanation reactions.

Cinchona-alkaloid-catalysed conjugate cyanation of enones has enabled the synthesis of trifluoromethyl-substituted diarylpyrroles with ee<96%P° Thiochro-manes have been formed by asymmetric domino sulfa-Michael-aldol reactions of 2-mercaptobenzaldehyde with a,/ -unsaturated A-acylpyrazoles. Asymmetric organocatalysed oxy-Michael addition to y-hydroxy a,/ -unsaturated thioesters on reaction with t-BuCHO has been used to form -hydroxy carbonyl compounds HOCH2C H(OH)CH2CO.SAr via cyclic hemiacetal intermediates. 

The enantioselective conjugate cyanations of electron-deficient alkenic acceptors were also reported by Ricci et al. [42], Deng et al. [51], and Shibata et al. [30] with cinchona-derived phase-transfer catalysts. Moreover, Deng and Shibata applied these conjugate additions of acetone cyanohydrin to develop the enantioselective catalytic routes to chiral dihydropyridazinones, pyrollines, and pyrrohdines, which are the core units of many bioactive compounds (Scheme 12.26). 

Scheme 12.26 Asymmetric phase-transfer catalytic conjugate cyanation of electron-deficient alkenes and its application to the synthesis of chiral dihydropyridazinones, pyrollines, and pyrrolidines.

The rearrangements 67 —> 70, 71 —> 72 and 74 —> 75 include the transformation of conjugated dienes to cumulenes. Nevertheless, these reactions take place with very high yields in some cases, because either an irreversible step of hydrolysis such as 69 —> 70 is involved or the very exothermic transformation from cyanates to isocyanates is used. Comparison of the energies, calculated by ab initio methods [121], shows that, for example, the energy of methyl isocyanate is lower than that of methyl cyanate by 26.8 kcal mol-1 and that of vinyl isocyanate is lower than that of vinyl cyanate by 28.1 kcal mol-1. 

Until recently, the Pd- or Ni-catalyzed cyanation had been performed most frequently with metal cyanides containing alkali metals, such as Na and K21a. More recently, however, the use of Zn(CN)2 in conjugation with DMF has been reported to be a useful alternative216 (Scheme 83). Further delineation of the relative merits and demerits among various metal countercations appears to be desirable. 

In the presence of Et20-B] 3. (Me3Si)2Se reacts with nitriles to give selenoamides while cyanates give the selenourea. Amides and tetramethylurea behave similarly, but the reaction with benzoates gives benzoin and 2,3,5,6-tetraphenyl-l,4-diselenin via selenoesters. These selenoesters can be trapped as conjugated diene cycloadducts (Scheme 5)78. 

The problem of the hydrocyanation of conjugated carbonyl compounds has been reviewed in detail by Nagata and Yoshioka [281. The reactions proceed smootltly and base or acid catalysts are sometime useful with HCN. Cyanides (KCN. NaCN. etc.) arc recommended reagents in some cases, particularly in nonaqueous Solvents (28], and even cyanohydrins (e.g., acetone cyanohydrin) have been used as cyanation reagents. 

The only other alkyne the anodic oxidation of which has been studied in detail is diphenylacetylene. Again it is difficult to be certain about the mechanism involved the phenyl group and the triple bond may be electroactive but, because of the conjugation between them, it is probably more rigorous to consider electron transfer from the molecule as a whole. The relevant oxidation potential is apparently 2 V (vs. S.C.E.), the potential employed for anodic cyanation. ... 

Cyanadons. Aluminum complexes of BINOLs (1) that are armed at C-3 and C-3 with diarylphosphine oxide groups possess both Lewis acid and base centers. Asymmetric cyanation of aldehydes and mines with MeaSiCN, and of quinolines and isoquinolines in a manner analogous to the Reissert reaction is successful (ee 70-90%). The asymmetric Strecker synthesis is applicable to conjugated aldimines and the higher reactivity of Me SiCN than HCN in the presence of 10 mol% of PhOH enables its use in catalytic amount while supplying stoichiometric HCN as the cyanide source. 

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