Acyclic secondary amines

The acid-catalyzed reaction of acetophenone with acyclic secondary amines results in the formation of the expected enamine and a rearrangement product. The latter product arises from the transfer of one of the amino N-alkyl groups to the cnamine s carbon to produce a ketimine (53a). 

TABLE 2. n ionization potentials (eV) of acyclic secondary amines R2NH... 

Reactant B 88 cyclic and acyclic secondary amines with molecular weights ranging from 71.2 to 162.1 Da... 

In general, alkylphosphines have been used less often than arylphosphines in crosscoupling chemistry. However, several studies pointed to the potential of such ligands in palladium-catalyzed animation of aryl halides. Most remarkable is the milder temperatures for animation of aryl bromides, improved yields with acyclic secondary amines, high turnover numbers for these reactions, and the ability to conduct mild animations of inexpensive aryl chlorides and tosylates. 

The lithium salts of acyclic secondary amines 92 can be conveniently transformed into the corresponding carbamoyllithiums 89 at —78 °C. Under these reaction conditions they react with trialkyltin chlorides to give carbamoyl stannanes 93 (Scheme 24)98. In the case of benzyl and allyl halides, an alkylation can occur affording products 94. However, when trialkylsilyl chlorides were used as electrophiles no carbamoyl silanes could be detected.. V-Alkyl thiocarbamates 95 can be prepared by reaction of the same intermediates 89 with sulfur followed by. S -alkylation at 0°C (Scheme 24)". 

The first intermolecular C-N bond-forming reactions between substituted 2-bromopyrroles 1450 and 1453 with primary (Tpropanamine, 2-methoxy-l-ethanamine, (4-methoxyphenyl)methanamine, cyclopropanamine, cyclobuta-namine), and cyclic secondary amines (pyrrolidine, morpholine, 1-methylpiperazine, ethyl tetrahydro-l(27/)-pyrazi-necarboxylate, 1-phenylpiperazine, l-(3-phenyl-2-propenyl)piperazine) 1451 were performed using Pd2(dba)3 as catalyst with BINAP as the ligand. The aminations proceeded in the presence of Bu ONa at 80-100 °C in 31-93% yields (Equations 301 and 302) <2004TL769>. However, when the above optimized conditions were applied to the coupling reaction of pyrrole 1450 and acyclic secondary amines such as di- -butylamine, diphenylamine and dipropenylamine, no reaction was observed. 

Reaction of Acyclic Secondary Amines with Aryl Chlorides. 154... 

Concurrently with this contribution from Buchwald and co-workers, the Hartwig group reported that the P(t-Bu)3P/Pd-catalyst system first reported by Koie and co-workers [36] is sufficiently active to couple aryl bromides with secondary amines at room temperature [50]. For example, 2-bromotoluene is efficiently aminated with morpholine at in 96% yield, Eq. (19). This catalyst is capable of the room temperature coupling of acyclic secondary amines and aryl bromides as well as the coupling of aryl chlorides at elevated temperatures. 

Hartwig and co-workers simultaneously described an improved procedure employing DPPFPdCl2, and added DPPF, as catalyst, Eq. (22) [29]. Considerable improvements in yield were observed using this DPPF/Pd catalyst to couple primary as well as acyclic secondary amines compared to (o-tol)3P-based systems. 

As was the case with ligand 4,2-biphenyldi-fert-butylphosphine (6) effects the amination of acyclic secondary amines at room temperature [42 a, 48]. The catalyst derived from this commercially available ligand and Pd2(dba)3 promotes the coupling of 4-bromo-ferf-butylbenzene and di- -butylamine or AT-methylaniline in excellent yields at room temperature, Eq. (28). 

Other groups have described systems that catalyze the arylation of acyclic secondary amines using aryl bromides, Eq. (32). Uemura reported the use of... 

---