[Ind₂TiMe₂]: ein Katalysator für die Hydroaminomethylierung von Alkenen und Styrolen

Abstract

Aufgrund der großen biologischen und industriellen Bedeutung von Aminen werden seit vielen Jahren Synthesemethoden gesucht, die einen möglichst einfachen Zugang zu dieser Substanzklasse ermöglichen. Hierbei sind die Hydroaminierung von Alkinen und Alkenen [1] sowie die metallkatalysierte Hydroaminoalkylierung von Alkenen [2][3][4][5][6][7] als 100 % atomökonomisch verlaufende Reaktionen von besonderem Interesse, da sie einfache Substrate unter C-N-bzw. C-C-Bindungsbildung direkt in komplexe Zielmoleküle überführen. Bei der Hydroaminoalkylierung von Alkenen wird die a-C-H-Bindung eines primären oder sekundären Amins aktiviert und an eine C-C-Doppelbindung addiert, wodurch die Amine in der a-Position zum N-Atom alkyliert werden. Während hierfür als Katalysatoren zunächst nur einfache Ta-Verbindungen zum Einsatz kamen, [3,4] gelangen kürzlich bereits erste enantioselektiv verlaufende Reaktionen unter Verwendung von Ta-Amidat-Katalysatoren.[5] Eine weitere Klasse von geeigneten Katalysatoren stellen die Komplexe der Gruppe IV dar, [6,7] wobei Zr-Katalysatoren nur für intramolekulare Reaktionen unter Verwendung primärer Aminoalkene eingesetzt wurden. [7] Demgegenüber eignen sich Ti-Katalysatoren wie [Ti(NMe 2 ) 4 ] und [TiBn 4 ] (Bn = Benzyl) sowohl für intra-als auch für intermolekulare Hydroaminoalkylierungen, und sie weisen eine erhöhte katalytische Aktivität auf.[6] Vergleicht man die bislang verfügbaren Daten über intermolekulare Hydroaminoalkylierungen von 1-Alkenen, so fällt auf, dass bei Verwendung von Ti-Komplexen zwei Regioisomere (verzweigt und linear, Schema 1) erhalten werden, während sich in Gegenwart von Ta-Komplexen ausschließlich das verzweigte Regioisomer bildet. Weiterhin auffällig an allen publizierten Studien zur intermolekularen Hydroaminoalkylierung von Alkenen ist, dass mit Styrolen bislang keine effizienten Umsetzungen beschrieben worden sind.[

A New N‐Trityl‐Substituted Aminopyridinato Titanium Catalyst for Hydroamination and Hydroaminoalkylation Reactions – Unexpected Intramolecular C–H Bond Activation

“…Although in all these cases formation of the branched regioisomer was favored, the regioselectivity of the reaction is obviously influenced by the nature of the halide substituent which led to a / b ratios between 79:21 and 88:12. In good agreement with the behavior of the hydroaminoalkylation catalyst Ind 2 TiMe 2 ,7d a much better regioselectivity ( a / b > 99:1) was observed during a reaction of the alkyl‐substituted alkene 1‐octene with N ‐methylaniline, which gave access to the pure branched regioisomer 9a in 96 % yield. The failure of additionally performed reactions with less reactive sterically demanding 1,1‐ and 1,2‐disubstituted alkenes like cyclohexene or β‐methylstyrene, which have already been achieved with Eisen's mono(formamidinate) complex7l finally proved the superiority of the latter hydroaminoalkylation catalyst.…”

“…Unfortunately, the poor yields obtained with II and III at 105 °C (Table 1, entries 1 and 2) lead to the additional conclusion that the activity of both catalysts with regard to hydroaminoalkylation reactions must be regarded as rather low. For example, much better yields (≥ 90 %) could be achieved with the catalyst Ind 2 TiMe 2 (Ind = η 5 ‐indenyl) at the same temperature 7d. However, on the other hand, it is worth mentioning that at 140 °C, the mono(2,6‐diaminopyridinato) catalysts II and III deliver mixtures of the desired hydroaminoalkylation products 3a and 3b in good yields of 90 % and 81 %, respectively (Table 1, entries 3 and 4).…”

“…As can be seen from Table 2, a number of interesting hydroaminoalkylation reactions could be achieved in the presence of 10 mol % II at 140 °C. Although the yields obtained with the sterically demanding substrates N ‐methyl‐ ortho ‐toluidine or ortho ‐methylstyrene, which result in the formation of the products 7a / b and 8a / b were only poor to modest, it is worth mentioning that many established catalysts do not catalyze hydroaminoalkylation reactions of sterically demanding substrates at all 5m,7d,7j. Another drawback of many existing titanium catalysts is that hydroaminoalkylation reactions using halogenated substrates often proceed sluggishly 7d,7g,7h.…”

“…Although the yields obtained with the sterically demanding substrates N ‐methyl‐ ortho ‐toluidine or ortho ‐methylstyrene, which result in the formation of the products 7a / b and 8a / b were only poor to modest, it is worth mentioning that many established catalysts do not catalyze hydroaminoalkylation reactions of sterically demanding substrates at all 5m,7d,7j. Another drawback of many existing titanium catalysts is that hydroaminoalkylation reactions using halogenated substrates often proceed sluggishly 7d,7g,7h. In this context, we were delighted to see that the products 10a / b , 11a / b , and 12a / b possessing halide substituents in the para position of the aniline system, which offer the possibility of further functionalization5k,13 were formed in reasonable yields (59–66 %).…”

Titanium Catalysts with Linked Indenyl–Amido Ligands for Hydroamination and Hydroaminoalkylation Reactions

“…Overall, it must be noted that, with regard to catalytic activity and regioselectivity, the investigated indenylethylamido titanium catalysts 3a−e cannot compete with the established hydroaminoalkylation catalyst Ind 2 TiMe 2 , which selectively gives access to the branched product 6a in higher yields under much milder reaction conditions. 14 In an additional study, the new dimethyl titanium complexes 3a−e were used as catalysts for cyclization reactions of aminoheptene 7 (Table 4), which can generally undergo two competing reactions: (i) intramolecular hydroamination to form a seven-membered azepane product or (ii) intramolecular hydroaminoalkylation, which delivers a six-membered aminocyclohexane product. In addition to the fact that, in this case, 3e turned out to lack any catalytic activity (Table 4, entry 5), it was interesting to note that all other dimethyl titanium complexes selectively catalyze the intramolecular hydroaminoalkylation of 7 at 140 °C and as a consequence, after derivatization, only the tosyl amide 9 was always obtained as a mixture of two diastereoisomers in a cis:trans ratio of approximately 1:4 (Table 4, entries 1−4).…”