Enantioselective copper-catalysed propargylic substitution: Synthetic scope study and application in formal total syntheses of (+)-anisomycin and (-)-cytoxazone
A copper catalyst with a chiral pyridine-2,6-bisoxazoline (pybox) ligand was used to convert a variety of propargylic esters with different side chains (R=Ar, Bn, alkyl) into their amine counterparts in very high yields and with good enantioselectivities (up to 90% enantiomeric excess (ee)). Different amine nucleophiles were applied in the reactions and the highest enantioselectivities were obtained for aniline and its analogues. Interestingly, some carbon nucleophiles could also be used and with indoles excellent ee values were obtained (up to 98% ee). The versatility of the propargylic amines obtained was demonstrated by their further elaboration to formal total syntheses of the antibiotic (+)-anisomycin and the cytokine modulator (-)-cytoxazone. Copyright
Detz, Remko J.,Abiri, Zohar,Le Griel, Remi,Hiemstra, Henk,Van Maarseveen, Jan H.
p. 5921 - 5930
(2011/06/26)
Copper-catalyzed enantioselective propargylic amination of propargylic esters with amines: Copper-allenylidene complexes as key intermediates
The scope and limitations of the copper-catalyzed propargylic amination of various propargylic esters with amines are presented, where optically active diphosphines such as Cl-MeO-BIPHEP and BINAP work as good chiral ligands. A variety of secondary amines are available as nucleophiles for this catalytic reaction to give the corresponding propargylic amines with a high enantioselectivity. The results of some stoichiometric and catalytic reactions indicate that the catalytic amination proceeds via copper-allenylidene complexes formed in situ, where the attack of amines to the electrophilic γ-carbon atom in the allenylidene complex is an important step for the stereoselection. Investigation of the relative rate constants for the reaction of several para-substituted propargylic acetates with N-methylanilines reveals that the formation of the copper-allenylidene complexes is involved in the rate-determining step. The result of the density functional theory calculation on a model reaction also supports the proposed reaction pathway involving copper-allenylidene complexes as key intermediates. The catalytic procedure presented here provides a versatile and direct method for the preparation of a variety of chiral propargylic amines.
(Chemical Equation Presented) A proper copper catalyst with a chiral pyridine-2,6-bisoxazoline (pybox) ligand was used to convert a variety of propargylic acetates with aromatic side chains (R = Ar) into their amine counterparts in high yield and with good selectivity (up to 88% ee). The resulting chiral propargylic amines can be elaborated further into P,N ligands (see scheme; DIPEA = diisopropylethylamine).
Detz, Remko J.,Delville, Marielle M. E.,Hiemstra, Henk,Van Maarseveen, Jan H.
p. 3777 - 3780
(2008/12/23)
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