Diynes, hydroamination

Aaron L. Odom of Michigan State University has described (Org. Lett. 2004, 6, 2957) a new approach to dialkyl pyrroles. Ti-catalyzed hydroamination of a 1,4-diyne such as 1 leads smoothly to 2. Similarly, Ti-catalyzed hydroamination of a 1,5-diyne such as 3 delivers 4. An inherent limitation of this approach is that it only allows substitution at the 2 and the 5 positions of the pyrrole. 

Titanium-catalyzed hydroamination of the diyne 470 has been demonstrated to proceed via a 5-r r/o- /g-cyclization affording the pyrrole 471 (Equation 130). Pyrroles have also been isolated as products from similar reactions involving related 1,5-diynes, which resulted from S-exo-dig-annuhitiom <2004OL2957>. 

Recent studies on the C—C cleavage reaction of diynes proceeded smoothly with Pd(NO3)3 as the best among all palladium catalysts tested [67]. Substituted benzoxazoles 115 and 116 along with alkanones were derived from C—C bond cleavage of diynes through hydroamination [68]. 

A titanium-catalyzed hydroamination of 1,4-diynes and 1,5-diynes produces 1,2,5-trisubstituted pyrrroles in one synthetic step <04OL2957>. Treatment of 1,4-diyne 33 with titanium complex 34 led to the formation of pyrrole 35 via a hydroamination to an imino alkyne followed by an intramolecular 5-endo dig cyclization. Another transition metal-mediated pyrrole... 

Schulte [285, 286] and later Chalk [287] described the Cu(I)-catalyzed synthesis of symmetrical 2,5-diarylpyrroles 261 from conjugated diynes 257 and primary amines 258. The reaction is believed to proceed via the transition metal-catalyzed hydroamination [33, 288-291] leading to tautomeric aminoenyne 259 or homopro-pargylic imine 260 intermediates, which further undergo 5-endo-dig cyclization to furnish pyrrole product 261 (Scheme 8.95). 

Alternatively, 1,3-diynes can also be used for the assembly of pyrroles, as has been shown by Bertrand [179], Odom [321], and Ackermann [324]. Skrydstrup showed that these easily accessed diyne starting materials can undergo efficient Au(I)-catalyzed hydroamination reactions with aniline derivatives to give trisubstituted... 

Scheme 15.99 Au-catalyzed hydroamination of 1,3-diynes for the synthesis of pyrroles.

Addition of primary amine to a 1,4- or 1,5-diyne could be accomplished using titanium complex Ti(NMe2)2(dpma), resulting in an imine-yne that can undergo cyclization to the pyrrole derivatives. The Markovnikov hydroamina-tion products of 1,4-pentadiyne could undergo 5-endo-dig cyclization to yield a 2-methylpyrrole. Meanwhile, Markovnikov hydroamination of 1,5-hexandiyne would yield an imine-yne that could undergo 5-exo-dig cyclization to a 2,5-dimethylpyrrole [314] (Scheme 14.135). 

A C=C triple bond of 1,3-diyne 149 was cleaved with 2-aminophenol in the presence of a ruthenium catalyst (Scheme 7.52) [71]. Initially, a ruthenium-catalyzed hydroamination takes place to give alkynyl imine 150. Conjugate addition of 2-aminophenol follows, resulting in the formation of the 1,3-diimine 151, which cyclizes to form the oxazoline 152. Subsequent retro-Mannich reaction cleaves the C-C bond to furnish the oxazole 153 and the imine 154. 

In recent years, synthesis of pyrroles has drawn the attention of chemists. Traditional methods used for pyrrole synthesis include the Hantzsch reaction [45] and the Paal-Knorr condensation reaction [46,47], The latter is the most widely used method, which involves the cyclocondensation reaction of 1,4-dicarbonyl compounds with primary amines to produce substituted pyrroles. In addition, there are several methods such as 1,3-dipolar cydoaddition reaction, aza-Wittig reaction, reductive coupling, and titanium-catalyzed hydroamination of diynes. Scheme 1 shows several catalysts used in this type of reaction [44]. 

When 1,5-diynes were subjected to the titanium-catalyzed reaction with aniline, regioselective hydroamination and subsequent 5-exo-dig cyclization resulted in the formation of the corresponding N-phenyl 2,5-substituted pyrroles ... 

Cobalt-mediated stereoselective assembly of 1-dienamides has also been described by VolUiardt recently. The process involves a hydroaminative alkyne coupling of a,(D-diynes and leads to a completely Z-selective formation of the diene moiety with a regiochemistry that depends on the substrate [179]. 

Hydroamination has been found to be useful in racemic synthesis of various natural products. Helquist and coworkers recently synthesized ( ) momomorine I using Ag-catalyzed hydroamination/cyclization of amino-diyne as the key step. Monomorine I is an indolizidine alkaloid isolated from ant Monomorium pharaoins. Beller and coworkers found hydroamination useful in the synthesis of amphetamines. It is worth mentioning that amphetamine is a class of compounds having several biological activities such as a stimulant to the central nervous system, an antiinflammatory agent, and inhibitors of enzymes. ... 

Iska VBR, Verdolino V, Wiest O, Helquist P. Mild and efficient desymmetrization of diynes via hydroamination application to the synthesis of ( )-monomorine 1. J. Org. Chem. 2010,75(4) 1325-1328. 

Poly(unsaturated) substrates can be used for sequential hydroamination/5-entio-cyclization reactions, which can be formally - but not mechanistically - seen as sequential inter/intramolecular hydroamination, to yield heterocyclic products, e.g., pyrroles from 1,4-diynes (30) [201]. 

---