Secondary aliphatic amines coupling

The thiophene ring is opened and sulfur extruded as hydrogen sulfide when 3,4-dinitrothiophene is reacted with piperidine. The product contains two nitroenamine units coupled to each other (Scheme 140). Other secondary amines react similarly (69CC549). Secondary aliphatic amines also react with 2-nitrothiophene to form the nitrodienamines (426) in 50-80% yield. It is believed that the reaction involves addition of the amine at position 5, followed by proton transfer and ring opening to give the thiol which, in the presence of air, oxidatively dimerizes to (426) (Scheme 141). In one case the thiol has been trapped as the silver salt and methylated (74JCS(P1)2357). 

Less reactive than acyl halides, but still suitable for difficult couplings, are symmetric or mixed anhydrides (e.g. with pivalic or 2,6-dichlorobenzoic acid) and HOAt-derived active esters. HOBt esters smoothly acylate primary or secondary aliphatic amines, including amino acid esters or amides, without concomitant esterification of alcohols or phenols [34], HOBt esters are the most commonly used type of activated esters in automated solid-phase peptide synthesis. For reasons not yet fully understood, acylations with HOBt esters or halophenyl esters can be effectively catalyzed by HOBt and HOAt [3], and mixtures of BOP (in situ formation of HOBt esters) and HOBt are among the most efficient coupling agents for solid-phase peptide synthesis [2]. In acylations with activated amino acid derivatives, the addition of HOBt or HOAt also retards racemization [4,12,35]. 

A highly regioselective amination of 6-aryl-2,4-dichloropyrimidines has been developed using palladium catalysis. The reaction which works well with secondary aliphatic amines and with anilines gives the 4-substituted products.46 Palladium catalysis has also been used in the regioselective coupling of 2,3-dibromopyridine with a series... 

A ligandless and base-free Gu-catalyzed protocol for the coupling of arylboronic acids and potassium aryltrifluoro-borates with primary and secondary aliphatic amines and anilines was developed. The process utilized catalytic copper(n) acetate monohydrate or CuCl2 and 4 AMS in dichloromethane at slightly elevated temperatures under an atmosphere of oxygen (Equation (232)).1019-1021... 

During the 1970 s,the lithium diethylamide catalyzed anionic telomerizations of myrcene 4, Eq. (2) [4] and isoprene, Eq. (3) [5] with secondary aliphatic amines were discovered. These reactions are highly chemo- and regioselective and opened the way for the production of various useful terpenoids. The selective formation of N,N-diethylnerylamine 5 from isoprene is noteworthy, because this reaction is only one example hitherto known that can effect isoprene coupling in the natural fashion. 

As stated previously, Q-phos shows perhaps the broadest scope for the Buchwald-Hartwig amination.45 Aryl chlorides are efficiently animated by all amine classes. The only coupling which gave poor yields was between ortho substituted aryl chlorides and acyclic secondary aliphatic amines. Typically, reaction temperatures of 70-100 °C are required and base sensitive aryl chlorides can be animated by replacing NaO/-Bu with K3PO4. 

Poly(phenylene oxides) are produced by the oxidative coupling of 2,6-disubstituted phenols. The polymers are also known as poly(oxyphenylenes) or poly(phenyl ethers), and, in the case of dimethyl compounds, also as poly(xylenols). Copper (I) salts in the form of their complexes with amines catalyze the reaction. Primary and secondary aliphatic amines must be used at low temperatures, since otherwise they are oxidized. Primary aromatic amines are oxidized to azo compounds, and secondary aromatic compounds probably to hydrazo compounds. Pyridine is very suitable. 

The tBu-XPhos ligand 28b embedded in the Pd(0) precursor X was particularly useful for the coupling of the smallest secondary aliphatic amine, dimethylamine, with aryl chlorides (Scheme 13.55) [108]. 

Combs and co-workers have pioneered the effort in the use of resin-supported substrates, reporting many examples of efficient cross-coupling of solid-supported sulfonamides [28c], primary and secondary aliphatic amines [28d], as well as het-eroarenes such as benzimidazoles, imidazoles, pyrazoles, and benzotriazoles [28e]. 

Primary aromatic amines (e.g., aniline) and secondary aliphatic-aromatic amines (e. g., 7V-methylaniline) usually form triazenes in coupling reactions with benzenedi-azonium salts. If the nucleophilicity of the aryl residue is increased by addition of substituents or fused rings, as in 3-methylaniline and 1- and 2-naphthylamine, aminoazo formation takes place (C-coupling). However, the possibility has also been noted that in aminoazo formation the initial attack of the diazonium ion may still be at the amine N-atom, but the aN-complex might rearrange too rapidly to allow its identification (Beranek and Vecera, 1970). 

The direct introduction of active groups on the polysaccharide and the protein could seriously affect the efficiency of the coupling by steric hindrance [114]. By direct attachment, the saccharide epitopes could be shielded by the secondary structure of the protein. To avoid this problem, a spacer arm is frequently introduced either on the modified CPS or on the protein carrier during the design of a glycoconjugate. The conjugates represented in Scheme 4 have been shown to be highly stable. They contained aliphatic amines [115], amides [116,117], or thioethers [118]. 

Lam and coworkers292 and Antilla and Buchwald297 expanded the scope of this type of catalytic coupling to encompass reactions of amines. Lam reported the coupling of aliphatic and aromatic amines, as well as heterocycles with N—H bonds with a combination of Cu(OAc)2 (10 mol%) and co-oxidants like pyridine A-oxide (PNO) or TEMPO in air. No single set of conditions led to coupling of all substrates. Concurrently, Buchwald reported reactions at room temperature catalyzed by Cu(OAc)2 (5-10 mol%) and myristic acid with stoichiometric amounts of 2,6-lutidine as base. Substituted anilines, as well as primary and secondary amines, reacted with a series of arylboronic acids. Excellent yields of arylated products were obtained for reactions of anilines, but only moderate yields were obtained for reactions of aliphatic amines. Yudin and coworkers employed this protocol to prepare A-aryl aziridines (equation 72)298. 

Quach and Batey299 reported the coupling of primary amines with phenylboronic acids catalyzed by Cu(OAc)2 (10 mol%) without base or ligand but in the presence of 4 A molecular sieves and air in CH2C12 solvent (equation 73). Reactions of potassium phenyl-trifluoroborate also occurred, but in lower yields than reactions of boronic acids. They showed that these reactions occur with a variety of functional groups on the amine, including alkenes, esters, ketones and ketals. a-Amino acid derivatives underwent reaction without detectable epimerization. Anilines were poorer cross-coupling partners under these conditions than were primary and secondary cyclic aliphatic amines. 

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