Chiral allene 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]. 

Figure 8.1 Gold complex used as catalyst for the hydroamination of axially chiral allenes.

Equation 11.12. Stereoselective gold catalyzed intermolecular hydroamination of a chiral allene [122]. 

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. 

Recently, the scope of gold-catalyzed intramolecular exo-selective hydroaminations was expanded to allenic hydrazines and hydroxylaminesJ The former substrates afforded pyrazolidines in the presence of DTBM-SEGPHOS-Au complex J, whereas [Au2 (R)-xylyl-BINAP (OPNB)2] gave the best results in the cyclization of hydroxylamine derivatives to isoxazolidines. Excellent chemical yields and enantioselectivities were obtained in most cases, and the method was also applied to the synthesis of chiral tetrahydrooxazines. 

The hydroamination of alkynes is a highly atom-efficient approach to the synthesis of enamines and imines, as well as to the synthesis of A-heterocyclic compounds such as indoles and pyrroles, which are widely occurring functional groups in biologically active molecules. Also included in this section is the hydroamination of allenes and alkenes, as the reaction of these substrates with chiral bimetallic catalysts has been shown to yield the chiral amine products with high enantioselectivity. 

While effective bimetallic catalyst design has the potential to lead to an enhancement of the reaction rate, the use of chiral bimetallic catalysts has also been explored to enhance the enantioselectivity of a reaction. Such bimetallic chiral induction is excellently demonstrated by the use of digold catalysts for the hydroamination of prochiral substrates such as allenes and alkenes [59]. The bimetallic Au catalyst 66, for example, was shown to be an effective catalyst for the hydroamination of amino-allenes in the presence of a silver salt activator (Scheme 24) [106]. The highest enantioselective induction for this reaction was achieved with a 1 1 ratio of AgBp4 to 66 (51 % ee) suggesting that the monocationic... 

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

Scheme 15.39 Hydroamination of allenes with transfer of chirality using an Au catalyst.

Asymmetric hydroamination has made a significant contribution toward the synthesis of chiral cyclic amines. Intramolecular asymmetric hydroamination of amino alkenes, amino alkynes, and amino allenes has been extensively studied to develop interesting strategies for the synthesis of chiral cyclic amines. 

It has been proposed that Au-catalyzed asymmetric hydroamination/cyclization of amino-allenes proceeds through a catalytic cycle demonstrated in Scheme 39.3. The chiral Au-complex activates the allenes generating the complex A, which is attacked by nitrogen to form species B. Species B upon protonolysis releases the product and regenerates the catalyst. 

To meet the demand, the compound has been successfully synthesized by hydroamination/ cyclization of amino-allene 13" ° (Scheme 39.7). Enantio-selective addition of n-dibutyl zinc to allenyl aldehyde 10 using a chiral Ti catalyst (generated by heating the mixture of 11 and Ti(Ot-Pr)4 in dry toluene at 40-45 °C for 30 minutes) provides the corresponding hydroxyl... 

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 Bronsted acid (242-245) catalysis of efficient, intramolecular hydroamination and hydroarylation reactions involving dienes or allenes (240), led to chiral pyrrolidines and isoxazolidines (241) in excellent yields and ee values (Scheme 63). ... 

Although hydroamination of allenes can be easily achieved with group 4 and group 5 metal catalysts, the stereoselectivity of these systems is rather limited. Several attempts to perform asymmetric hydroamination/cyclization of aminoallenes employing chiral aminoalcohols [260, 261] and sulfonamide alcohols [262] as chiral proligands for titanium- and tantalum-based catalyst systems have produced vinyl pyrrolidines with low selectivities only. While the titanium catalysts were... 

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