Enantioselective nickel-catalysed cycloaddition reactions

Reactions which form multiple bonds, rings, and stereocentres are partieu-larly important tools for the efficient assembly of complex moleeular strue-tures. Of the many families of reactions discovered over the past eentury, cycloaddition reactions hold a prominent place in the arsenal of synthetie methods currently available to organic chemists, and research activity in this field shows no signs of abatement. Among the metals used to catalyse cyc-loadditions, nickel has been found competent to promote enantioselectively the formation of carbo- and heterocycles of various ring sizes. 

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In the last decade, several excellent results were also published in the area of enantioselective nickel-catalysed Diels-Alder cycloadditions. Among them, the reactions of cyclopentadiene with 3-alkenoyloxazolidin-2-ones induced by (i )-BINIM-2QN provided cycloadducts in up to >99% yield, >98% de, and 96% ee. Another excellent result was achieved by using a chiral iV,iV -oxide-derived nickel catalyst in Diels-Alder cycloadditions of 3-vinylindoles with methyleneindolinones for the construction of chiral spiro[carbazole-oxindoles] in up to 97% yield, >98% de, and 98% ee. Moreover, the use of the chiral DBFOX-Ph ligand has allowed an inverse-electron-demand Diels-Alder reaction of a range of Af-sulfonyl-l-azadienes with vinyl ethers to be achieved, providing highly functionalised piperidines in up to 75% yield, 96% de, and 92% ee. 

Earlier, Kurahashi and Matsubara described regio- and enantioselective nickel-catalysed decarbonylative formal cycloadditions of phthalic anhydrides with allenes to give in a single step the corresponding chiral 5-lac-tones. The process represented an unprecedented insertion reaction of a carbon-carbon double bond into a carbon-oxygen bond. It was performed in the presence of a chiral nickel catalyst generated in situ from Ni(cod)2 and (5,5)-i-Pr-FOXAP in pyridine at reflux. The chiral 5-lactones were achieved in both moderate to good yields (64-73%) and with enantioselectivities of 59-81% ee, as shown in Scheme 4.16. Better yields (73-90%) and enantioselectivities... 

The nickel-iminophosphine-catalysed 4- -2-cycloaddition of enones with allenes formed highly substituted dihydropyrans. The enantioselective amine-catalysed 4-I-2-cycloaddition of allenoates with oxo-dienes produced polysubstituted dihydropyrans in high yields and with high enantioselectivities. Novel enam-ine/metal Lewis acid bifunctional catalysis has been used in the asymmetric inverse-electron-demand hetero-Diels—Alder reactions of cyclic ketones with Q ,j9-unsaturated a-ketoesters. The 4- -2-cycloaddition of acylketenes (80) with 2-unsubstituted and 2-monosubstituted 3-aryl-2//-azirines (81) produced 1 1 (82) or 2 1 (83) adducts, being derivatives of 5-oxa-l-azabicyclo[4.1.0]hept-3-ene or 5,7-dioxa-l-azabicyclo[4.4.1]undeca-3,8-diene. The formation of the monoadducts proceeds via a stepwise non-pericyclic mechanism (Scheme 25). A-heterocyclic carbene-catalysed 4- -2-cycloaddition of ketenes with 1-azadienes yielded optically active 3,4-dihydropyrimidin-2-ones (93% ee) ... 

The enantioselective intramolecular formal 2+4-cycloaddition of acrylates and a, -unsaturated imines (99) catalysed by chiral phosphines (100), derived from amino acids, produced A-heterocycles (101) (Scheme 31). Chiral dirhodium(II) carboxamidates (102) catalysed the hetero-Diels-Alder reactions between 2-aza-3-silyloxy-l,3-butadienes and aldehydes to yield all cw-substituted l,3-oxazinan-4-ones in high yields and high enantioselectivity (98% ee)P The nickel-catalysed 4 + 2-cycloaddition of a, -unsaturated oximes with alkynes yielded 2,3,4,6-tetrasubstituted pyridine derivatives. The reaction of isoquinoline, an activated alkyne, and 4-oxo-4//-l-benzopyran-3-carboxaldehyde (103), in ionic solvents, produced 9a//,15//-benzo[a][l]benzopyrano[2,3-/t]quinolizine derivatives (105) via the zwitterion (104) selectively and in good yields (Scheme 32).The Diels-Alder cycloaddition of ethyl 3-(tetrazol-5-yl)-l,2-diaza-l,3-butadiene-l-carboxylates with -rich heterocycles, nucleophilic olefins, and cumulenes formed 3-tetrazolyl-l,4,5,6-tetrahydropyridazines regioselectively. The silver-catalysed formal inverse-electron-demand Diels-Alder... 

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