Enantioselectivity hydroamination

At the end of 2007, Widenhoefer et al. reported the first examples of the dynamic kinetic enantioselective hydroamination of axially chiral allenes, catalyzed by a dinuclear complex of gold (Figure 8.1) and silver perchlorate [46, 47]. 

The enantioselective hydroaminations of allenes with chiral phosphine catalysts was accomplished with substrates that had a terminal symmetric substitution and with the amines protected as carbamates or sulfonamides. The same symmetric substituents were necessary for the enantioselective transformation nsing chiral counterions. However, very recently, high enantiomeric excesses were reached with trisubstituted asymmetric allenes by a dynamic kinetic enantioselective hydroamination of allenyl carbamates (eqnation 110), even thongh the E/Z ratio of the prodncts was not optimal. 

Wang, Q.W., Xiang, L., Song, H.B. et al. (2008) Synthesis of amidolanthanides with new chiral biaryl-based NNO ligands and their use as catalysts for enantioselective hydroamination/cycUzation. Inorganic Chemistry, 47, 4319. 

A number of (R)- and (,S )-organolanthanide alkyl and amide complexes 1, bearing a homochi-ral substituent R on one cyclopentadienyl ring, were prepared and their catalytic activity in the enantioselective hydroamination-cyclization of 4-pentenylamines 3 was examined 11 113 These complexes are converted to the catalytically active species 2 in the presence of a large excess of the amine. Furthermore, catalyst epimerization (S)-2 to (/ )-2 or vice versa occurs and is complete in the early stages of preparative-scale reactions however, equilibrium homochiralities are frequently high, in some cases >95%. 

Equation 11.7. Enantioselective hydroamination/cyclization of internal aminoalk enes [39]. 

Palladium-based catalysts for enantioselective hydroamination reactions were discovered by extending the results of a high-throughput screening approach directed toward the discovery of non-selective hydroamination catalysts, reported by the Hartwig group in 2001. The approach taken by Hartwig and co-workers is described in Section 1.13.2.5. ... 

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

Scheme 24 Different reactivities and selectivities of chiral bimetallic Au complexes used in the enantioselective hydroamination reaction of amino-allenes...

Toste has described the intramolecular enantioselective hydroamination of y- and 6-aUenyl sulfonamides catalyzed by enantiomerically pure bis(gold) phosphine complexes [42]. For example, treatment of the terminally-disubstituted y-allenyl sulfonamide 59 with a catalytic amount of [(R)-3,5-xylyl-binap](AuOPNB)2 (OPNB =p-nitrobenzoate) formed protected pyrrolidine 60 in 88% yield with 98% ee (Eq. (11.34)). Likewise, treatment of 6-allenyl sulfonamide 61 with a catalytic amount of [(JJ)-Cl-MeObiphep](AuOPNB)2 in nitromethane at 50 °C for 24h formed 2-alkenyl piperidine 62 in 70% isolated yield with 98% ee (Eq. (11.35)). Realization of high enantioselectivity in this protocol required employment of both a terminally disubstituted allene and a sulfonamide nucleophile. 

Another enantioselective hydroamination of this type was attained via the transient formation of aminal (37) from its precursors, namely hydroxylamine (34) and amine (35), in the presence of the chiral aldehyde (36) as catalyst. The vicinal diamines (38) thus obtained were of <97% This retro-Cope chemistry, in particular the concept... 

Marks showed in the 1990s that the cyclohydroamination of alkenes was catalyzed by organolanthanide complexes and, in 2000, Hartwig reported the enantioselective hydroamination of p-trifluromethylstyrene by aniline using Noyori s catalyst [R-BINAP-Pd(0S02CF3)2] (toluene, 45°C, 81% yield, 81% ee). 

Knight PD, Munslow I, O Shaughnessy PN, Scott P. Zirconium catalysed enantioselective hydroamination/cyclization. Chem. Commun. 2004 (7) 894—895. 

Zhang Z, Bender CF, Widenhoefer RA. Gold(I)-catalyzed enantioselective hydroamination of A-aUenyl carbamates. Org. Lett. 2007 9(15) 2887-2889. 

A 1 2 mixture of [ (5)-(235) (AuCl)2] and AgBp4 has been reported to catalyse the enantioselective hydroamination of chiral, racemic 1,3-disubstituted allenes ArCH=C=CHMe with A-unsubstituted carbamates to form A-allylic carbamates ArCH=CHCH(NHCbz)Me in <92 % ee ... 

The asymmetric hydroamination constitutes a facile and atom-economical approach to chiral amines. The rational design of efficient, configurationally stable and highly selective catalysts has become an area of intense research activity. Significant progress has been made in the area of intramolecular enantioselective hydroamination, while... 

Fig. 16 Stereomodel for enantioselective hydroamination/cyclization using bisoxazolinate lanthanum catalyst 58 [219]. The structure of the bisoxazolinate ligand is simplified for clarity...

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