Hydroamination and Hydroaminoalkylation

Selected examples of niobium-mediated asymmetric reaction (pioneering work), Diels-Alder reaction (a) J. Howarth and K. Gillespie, Molecules, 2000, 5, 993-997 Mannich-type reaction (b) S. Kobayashi, 

Review on bioinorganic chemistry of vanadium D. Rehder, Angew. Chem., Int. Ed. Engl., 1991, 30,148-167 

Recent reviews on the asymmetric oxidations (a) A. J. Burke, E. P. Carreiro, Asymmetric epoxidation and sulfoxidation, in Comprehensive Inorganic Chemistry II, ed. J. Reedijk and K. Poeppelmeier, 2013, vol. 6, pp. 309-382 (b) H. Srour, P. L. Maux, S. Chevance and G. Simonneaux, Coord. Chem. Rev., 2013, 257, 3030-3050. 

Enantioselective cyanation of carbonyls and imines, in Comprehensive Chirality, ed. E. M. Carreira and H. Yamamoto, 2012, vol. 4, pp. 315-327 (b) T. V. RajanBabu, Hydrocyanation in organic synthesis, in Comprehensive Organic Synthesis, ed. P. Knochel, 

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Scheme 15 Bis(pyridonate) bis(dimethylamido) zirconium complex 14 that promotes both hydroamination and hydroaminoalkylation...

Doye s group [81] showed that a dinuclear titanium-sulfonamidate complex (Scheme 21), with a tetrahedral sulfur in the ligand backbone, can be used for intermo-lecular hydroaminoalkylation as well. This system gives mixtures of branched and linear products, although to date there has been no mechanistic rationale provided for the reduced regioselectivity of group 4 metal complexes in this transformation. There has been one report by Zi s group [44] that describes axially chiral bis(sulfonamidate) tantalum and niobium complexes for application as precatalysts for hydroamination and hydroaminoalkylation. Unfortunately, these complexes did not show any reactivity for either of these reactions. 

Scheme 9.30 Enantioselective hydroamination and hydroaminoalkylation using a chiral 3,3 -silylated binaphtholate niobium complex, reported by Hultzsch. ...

To this end, a titanium bis(2-pyridonate) complex (17) has been developed. [22c] These catalytic systems promote catalyst-controlled selectivity for hydroaminoalkylation over hydroamination and for the first time amine-substituted cyclopentanes can be prepared preferentially over piperidine hydroamination products (Scheme 25). 

Scheme 23 Cyclization of primary aminoalkenes can result in mixtures of hydroaminoalkylation and hydroamination products...

The formation of such bridged metallaziridine species rationalizes the selectivity for primary amines and suggests that dimeric species may be key catalytic intermediates. This is further supported by experiments that illustrated that increasing catalyst concentration results in an increase in hydroaminoalkylation product versus hydroamination product. [72] Therefore, we proposed that catalyst-controlled chemoselectivity for hydroaminoalkylation (C—C bond formation) versus hydroamination (C—N bond formation), could be achieved by designing catalyst systems that promote the formation of bridged species. 

In 2013, Schafer reported 2-pyridonate titanium eomplexes as eatalysts for the ehemoselective intramoleeular hydroaminoalkylation of aminoalkenes rather than hydroamination, obtaining five- and six-membered cycloalk-ylamines in good to excellent yields. ... 

Enantioselective vanadium and niobium catalysts provide chemists with new and powerful tools for the efficient preparation of optically active molecules. Over the past few decades, the use of vanadium and niobium catalysts has been extended to a variety of different and complementaiy asymmetric reactions. These reactions include cyanide additions, oxidative coupling of 2-naphthols, Friedel-Crafts-type reactions, pinacol couplings, Diels-Alder reactions, Mannich-type reactions, desymmetrisation of epoxides and aziridines, hydroaminations, hydroaminoalkylations, sulfoxida-tions, epoxidations, and oxidation of a-hydroxy carbo) lates Thus, their major applications are in Lewis acid-based chemistiy and redox chemistry. In particular, vanadium is attractive as a metal catalyst in organic synthesis because of its natural abundance as well as its relatively low toxicity and moisture sensitivity compared with other metals. The fact that vanadium is present in nature in equal abundance to zinc (albeit in a more widely distributed form and more difficult to access) is not widely appreciated. Inspired by the activation of substrates in nature [e.g. bromoperoxidase. 

Hydroamination is an atom-economical process for the synthesis of industrially and pharmaceutically valuable amines. The hydroamination reaction has been studied intensively, including asymmetric reactions, and a variety of catalytic systems based on early and late transition metals as well as main-group metals have been developed." However, Group 5 metal-catalysed hydroaminations of alkenes had not been reported until Hultzsch s work in 2011. Hultzsch discovered that 3,3 -silylated binaphtho-late niobium complex 69 was an efficient catalyst for the enantioselective hydroaminoalkylation of iV-methyl amine derivatives 70 with simple alkenes 71, giving enantioselectivities up to 80% (Scheme 9.30). Enantiomerically pure (l )-binaphtholate niobium amido complex 69 was readily prepared at room temperature in 5 min via rapid amine elimination reactions between Nb(NMe2)5 and l,l-binaphthyl-2-ol possessing bullqr 3,3 -silyl substituents. Since the complex prepared in situ showed reactivity and selectivity identical... 

Neutral group 4 metal complexes appear to possess a relatively broad scope for catalytic hydroaminations. They have been employed for the intramolecular hydroamination of alkynes [2], allenes [3], and alkenes [4] as well as the inter-molecular hydroaminations of alkynes [5] and allenes [6]. Primary aryl- and alkylamines readily react, but secondary amines have posed a greater challenge for this type of transformation with neutral catalysts [7]. For the reactions of the latter, cationic Zr and Ti complexes have been employed in intramolecular cyclizations of aminoalkenes [8]. Very recent work suggests that substrates that are difficult to hydroaminate may favor hydroaminoalkylations instead (Scheme 13.2) [9]. 

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