Iridium-Catalyzed [2 + 2 + 2] Cycloaddition of α,ω-Diynes with Nitriles

Abstract

[Ir(cod)Cl](2)/DPPF or BINAP efficiently catalyzed the cycloaddition of α,ω-diynes with nitriles to give pyridines. The reaction can accommodate a very wide range of nitriles. Both aliphatic and aromatic nitriles smoothly reacted with α,ω-diynes to give pyridines. Ten equivalents of unactivated aliphatic nitrile were enough to give the product in high yield. Aliphatic nitriles bearing an acetal or amino moiety could be used for the reaction. The highly regioselective cycloaddition of unsymmetrical diyne bearing two different internal alkyne moieties was achieved. The observed regioselectivity could be reasonably explained by considering the different reactivities of the α-position in iridacyclopentadiene. Regioselective cycloaddition was successfully applied to the synthesis of terpyridine and quinquepyridine. This chemistry was extended to a new and efficient synthesis of oligoheteroarenes. Five aromatic or heteroaromatic rings were connected in a single operation. [Ir(cod)Cl](2)/chiral diphosphine catalyst can be applied to enantioselective synthesis. Kinetic resolution of the racemic secondary benzyl nitrile catalyzed by [Ir(cod)Cl](2)/SEGPHOS gave a central carbon chiral pyridine in 80% ee. The mechanism was analyzed on the basis of the B3LYP level of density functional calculations.

Iridium‐Catalyzed [2+2+2] Cycloaddition of α,ω‐Diynes with Cyanamides

“…Thek ey intermediate in the cycloaddition is iridacyclopentadiene [22] which is formed by the oxidative cyclization of a,w-diyne to iridiumd iphosphines pecies.T he reactiono fi ridacyclopentadiene with cyanamide gives the 2-aminopyridine product.T he regioselectivity of the reactiono fa nu nsymmetrical diyne is determined when iridacyclopentadiene reacts with the carbon-nitrogen triple bond in cyanamide.I no ur previousp aper, [19] we showedt hat the regioselectivity of the reactionw ith nitriles was controlled by an electronice ffect. Specifically,t he more electron-deficient a-carbon preferentially reacts with the more electronrich nitrile nitrogen.…”

“…[19] Ther egioselectivity couldb er easonably explained by the electronic effect of as ubstituento na na lkyne carbon. Ther egioselectivity of the reactions of unsymmetrical internald iynes with cyanamides has been examined.…”

“…Consequently,atrimethylsilyl-substituted a-carbon reacts with am ore electron-deficient nitrile carbon to give 5pa and 5pd.T he steric effect of at rimethylsilyl group should lead to the formation of the less-hindered product 4pa and 4pd.H owever, the absence of the less-hindered product shows that the steric effect does not determine the regioselectivity.W hy doesn't the sterice ffect of at rimethylsilyl group determine the regioselectivity?T he DFT calculation for the reaction mechanism in our previous papers howedc onsecutiveb ond formation between iridacyclopentadiene andn itrile (Scheme 2). [19] Nitrile coordinates to Scheme1.Regioselective reactiono fi ridacyclopentadienes 6n-q with cyanamide 2. [a] Am ixture of diyne 1 (1 mmol), cyanamide 2a or 2d (1.2 mmol), [Ir(cod)Cl] 2 (0.01 mmol), ligand (0.02 mmol) and benzene (2.5 mL) was stirredu nder refluxing for 24 h. [b] Isolated yield based on the amount of 1.…”

“…In our previouss tudy,w ee xamined the reactionm echanism of the model reactions ystemf or iridium-catalyzed cycloaddition with nitriles by using DFT calculations,a nd proposed ar eactionp athway where the iridacyclopentadiene generated by oxidative cyclization of a,w-diyne reacts with nitrile to give the iridium pyridine complex via an azairidabicyclo[3.2.0]heptatriene complex. [19] Based on the results, we furtherc arriedo ut B3LYP DFT calculations [24,25] (LANL2DZ [26] for Ir atom and 6-31G* [27] for other atoms) to examine the reactionp athwayf rom the iridacyclopentadiene to the h )o fII is 4.5 kcalmol À1 . [28] Thef irst bond formation between the cyanamide carbon and the C-5 atom gives the azairidabicyclo[3.2.0]heptatriene complex III through transitions tate TSI.…”

“…[19] Oneo ft he advantageso f[ Ir(cod)Cl] 2 catalyst over other transition metals,especially Cp-or Cp*-coordinated transitionm etals,i st hat we can alter the catalytic activity ands electivity by choosing appropriate phosphines.T he iridium-catalyzed reaction has ab roader scope of nitriles,s ince both functionalized nitriles and unactivated nitriles can be used. Ourp revious study [19] showed that a-o rb-aminonitrile was ag oodc oupling partner for a,w-diynes.A na mino group didn ot inhibit the reactiond espite its ability to coordinate to the iridiumc enter. This result prompted us to examine the cycloaddition with cyanamide in which an amino group is directly connected to anitrile carbon.…”