Practical and Efficient Synthesis of C₂ Symmetrical Diamines with Zn/Me₃SiCl

Abstract

C 2 symmetrical diamines are efficiently obtained by reductive coupling of imines with the couple Zn/Me 3 SiCl. This high yielding method is very practical and cheap for large scale preparation.Chiral C 2 symmetrical diamines are among the most promising chiral auxiliaries in asymmetric synthesis. 1 Our group is strongly involved in this field, 2 and new practical methods are needed to prepare, in bulk, a variety of such diamines. Among the various ways of preparation, the pinacol-type coupling of imines seems the most attractive. The use of a low valent metal for such a reductive coupling is known since 1908, 3 and several metals have since been used. 4 Most of them, however, suffer from high cost or practical problems in scaling up, such as filtration and isolation of the desired diamine. Scheme 1The coupling reaction usually affords the useful racemic d,l diamine, the useless meso diamine and variable amounts of reduction material. We present herein a very practical and high yielding method, which is even more efficient when associated with the isomerization of the meso diamine into the d,l one, as described in the following article.The reductive properties of the cheap metal Zn(0) have been known for a long time, 5 and the combination of Zn and Me 3 SiCl (TMSCl) has been used previously for the coupling of carbonyl compounds. 6 The reductive dimerization of isoquinoline has also been observed in the presence of Li or Mg and TMSCl. 7

Metallierung und C-C-Kupplung von 2-Pyridylmethylamin: Synthese und Strukturen von Methylzink-2-pyridylmethylamid, Tris(trimethylsilyl)methylzink-2-pyridylmethylamid und (Z)-1-Amino-1,2-bis(2-pyridyl)ethen

“…Chirale C 2 -symmetrische 1,2-Diaminoethane finden in der asymmetrischen Synthese vielfältige Anwendung [22] und lassen sich durch die reduktive C-C-Kupplung von Iminen mit Metallen wie Zink [23], Aluminium [24], Bismut und anderen [24] darstellen. Die Reduktion der Imine mit Zink wird vorteilhaft in Anwesenheit von Chlortrimethylsilan durchgeführt [23].…”

“…Die Reduktion der Imine mit Zink wird vorteilhaft in Anwesenheit von Chlortrimethylsilan durchgeführt [23]. Die von uns entwickelte Darstellung solcher 1,2-Diaminoethane mit Hilfe der oxidativen C-C-Kupplungsreaktion aus 2-Pyridylmethylaminen mit Dialkylzink gelingt nahezu quantitativ, wenn Trialkylsilyl-Substituenten am Stickstoffatom die oben geschilderten Nebenreaktionenswege unterbinden.…”

Synthesis of 1,4-Diamino-2,3-di(2-pyridyl)butane and its Dinuclear Zinc(II) Chloride Complex

“…The reductive coupling of imines with aluminum or bismuth in methanol in the presence of KOH also gave vicinal diamines [4]. A variant of this reaction employed a mixture of zinc and chloro-trimethylsilane as reducing agents and allowed the synthesis of A (R = Me) [5] whereas lithium is not a suitable reducing reagent if pyridyl groups are present in the molecules [6]. Low-valent titanium species, produced from TiCl 4 and magnesium amalgam, were also able to reductively couple N-(2-pyridylmethylidene)-methylamine [7].…”

Lithium and Zinc Complexes of C‐ and N‐Functionalized (2‐Pyridylmethyl)amines

“…(2) This oxidative C-C coupling of N-(trialkylsilyl)-protected picolylamines leads to C 2 -symmetric complexes C. Another pathway offers the reductive C-C coupling of imines with metals (such as Zn/Me 3 SiCl, Mg/Me 3 SiCl, Al or Bi) to the 1,2-diaminoethanes F according to Equation (3), however, also minor amounts of reduction products, amines G, are formed occasionally. [19,20] (3)…”

“…Whereas acetamide yields the protolysis product E, aniline gives rise to substitution product H. [18] Experiments with [ 15 N]aniline show that protontransfer reactions lead to this unusual reaction behaviour and that not only the trialkylsilyl groups are replaced by phenyl substituents but the NSiR 3 units against NPh moieties. (4) The oxidative C-C coupling of 2-pyridylmethylamines with organometallic compounds such as dimethylzinc or Sn[N(SiMe 3 ) 2 ] 2 [11,12] as well as the reductive C-C coupling of imines [19,20] yield C 2 -symmetric chelate Lewis bases. In order to develop unsymmetric tetradentate ligands which are able to form polynuclear complexes, other synthetic strategies have to be applied.…”