Amines alkyne

Finally, Odom and co-workers reported a titanium-catalyzed three-component coupling between primary amines, alkynes, and isonitriles for the preparation of a, 3-unsaturatcd /3-iminoamines in good yields (Scheme 35).121 Beside the three-component coupling product, an. V,.V-disubstituted formamidine and an imine were also identified as minor... 

Scheme 8 Proposed mechanism for pyrrole synthesis from an amine, alkyne, and CO via zirconaaziridine...

On the basis of these observations and the known structures of a few polynuclear copper complexes, we suppose that CuC=CR is a part of a soluble complex, e.g. structure 26 . The coordination number of the copper is probably 4 and the ligands (L) may be amine, alkyne, etc. In the coupling reaction, the slow step is the release or transfer of X from carbon. These speculations lead to something like the progression in equation (271). 

Vibrational micro mill, stainless steel jar (50mL), 2x15mm balls, 25Hz, aldehyde amine alkyne Cu(OTf)2 , 1 1.2 2 0.1 0.1, silica gel. 

In 2008, Li et al. reported a copper-catalyzed amine-alkyne-alkyne addition reaction as an efficient method for the synthesis of Y,5-alkynyl-p-amino acid derivatives 102 (Scheme 3.52) [137]. In this case, the first step of the reaction is proposed to be the hydroamination of the electron-deficient alkyne 100, which plays the role of the aldehyde component. Subsequent reaction of the resultant intermediate XXX with alkyne 101 would afford intermediate XXXI, which would be then protonated to give an iminium intermediate XXXII. Finally, an intramolecular transfer of the alkyne moiety to the iminium ion would yield the 7,8-alkynyl-p-amino ester 102 and regenerate the catalyst. The reaction was later extended using chiral prolinol derivatives as the amine component, which afforded the corresponding Y,5-alkynyl-p-amino acid derivatives with excellent diaste-reoselectivities (up to >99 1) [138]. 

SCHEME 3.52 Cu-catalyzed amine-alkyne-alkyne coupling reaction. 

W.-J. Yoo, C.-J. Li, Adv. Synth. Catal. 2008, 350, 1503-1506. Copper-catalyzed four-component coupling between aldehydes, amines, alkynes, and carbon dioxide. 

J. Zhao, H. Huang, C. Qi, H. Jiang, Eur. J. Org. Chem. 2012, 2012, 5665-5667. CuI/SnCl Co-catalyzed four-component reaction of ketones, amines, alkynes, and carbon dioxide. 

L. Zhou, Q. Shuai, H.-F. Jiang, C.-J. Li, Chem.-Eur. J. 2009, 15, 11668-11674. Copper-catalyzed amine-alkyne-alkyne addition reaction an efficient method for the synthesis of y,5-alkynyl-P-amino acid derivatives. 

CO. Alkynes will react with carbon monoxide in the presence of a metal carbonyl (e.g. Ni(CO)4) and water to give prop>enoic acids (R-CH = CH-C02H), with alcohols (R OH) to give propenoic esters, RCH CHC02R and with amines (R NH2) to give propenoic amides RCHrCHCONHR. Using alternative catalysts, e.g. Fe(CO)5, alkynes and carbon monoxide will produce cyclopentadienones or hydroquinols. A commercially important variation of this reaction is hydroformyiation (the 0x0 reaction ). 

There also exists an acidregioselective condensation of the aldol type, namely the Mannich reaction (B. Reichert, 1959 H. Hellmann, 1960 see also p. 291f.). The condensation of secondary amines with aldehydes yields Immonium salts, which react with ketones to give 3-amino ketones (=Mannich bases). Ketones with two enolizable CHj-groupings may form 1,5-diamino-3-pentanones, but monosubstitution products can always be obtained in high yield. Unsymmetrical ketones react preferentially at the most highly substituted carbon atom. Sterical hindrance can reverse this regioselectivity. Thermal elimination of amines leads to the a,)3-unsaturated ketone. Another efficient pathway to vinyl ketones starts with the addition of terminal alkynes to immonium salts. On mercury(ll) catalyzed hydration the product is converted to the Mannich base (H. Smith, 1964). 

The formation of disubstituted alkynes by coupling of terminal alkynes, followed by intramolecular attack of an alcohol or amine, is used for the preparation of benzofurans and indoles. The benzo[il)]furan 356 can be prepared easily by the reaction of o-iodophenol with a terminal alkyne[262]. The 2-substituted indole 358 is prepared by the coupling of 2-ethynylaniline (357) with aryl and alkenyl halides or triflates, followed by Pd(ll)-catalyzed cycliza-tion[263]. 

In addition to alcohols, some other nucleophiles such as amines and carbon nucleophiles can be used to trap the acylpalladium intermediates. The o-viny-lidene-/j-lactam 30 is prepared by the carbonylation of the 4-benzylamino-2-alkynyl methyl carbonate derivative 29[16]. The reaction proceeds using TMPP, a cyclic phosphite, as a ligand. When the amino group is protected as the p-toluenesulfonamide, the reaction proceeds in the presence of potassium carbonate, and the f>-alkynyl-/J-lactam 31 is obtained by the isomerization of the allenyl (vinylidene) group to the less strained alkyne. 

Carbonylation of the tetrasubstituted bispropargyiic amine 23 using PdCP and thiourea under mild conditions affords the carboxylated pyrrolidine derivatives 24a and b in good yields. Thiourea is regarded as effective for the oxidative carbonylation of alkynes, but no oxidative carbonylation was observed in this case[21]. 

Amines undergo aminopalladation to alkynes. The intramolecular addition of amines to alkynes yields cyclic imines. The 3-alkynylamine 273 was cyclized to the 1-pyrroline 274, and the 5-alkynylamine 275 was converted into the 2,3,4,5-tetrahydropyridine 276[137]. Cyclization of o-(l-hexynyl)aniline (277)... 

General Reaction Chemistry of Sulfonic Acids. Sulfonic acids may be used to produce sulfonic acid esters, which are derived from epoxides, olefins, alkynes, aHenes, and ketenes, as shown in Figure 1 (10). Sulfonic acids may be converted to sulfonamides via reaction with an amine in the presence of phosphoms oxychloride [10025-87-3] POCl (H)- Because sulfonic acids are generally not converted directiy to sulfonamides, the reaction most likely involves a sulfonyl chloride intermediate. Phosphoms pentachlotide [10026-13-8] and phosphoms pentabromide [7789-69-7] can be used to convert sulfonic acids to the corresponding sulfonyl haUdes (12,13). The conversion may also be accompHshed by continuous electrolysis of thiols or disulfides in the presence of aqueous HCl [7647-01-0] (14) or by direct sulfonation with chlorosulfuric acid. Sulfonyl fluorides are typically prepared by direct sulfonation with fluorosulfutic acid [7789-21-17, or by reaction of the sulfonic acid or sulfonate with fluorosulfutic acid. Halogenation of sulfonic acids, which avoids production of a sulfonyl haUde, can be achieved under oxidative halogenation conditions (15). 

---