An operationally simple and scalable synthesis of enantiomerically pure bicyclo[2.2.2]octadiene (bod*) ligands relying on an organocatalytic one-pot Michael addition-aldol reaction with cheap 2-cyclohexenone and phenylacetaldehyde is presented. The crystalline bicyclic product 4a (6-hydroxy-5-phenylbicyclo[2.2.2]octan-2-one) is transformed into phenylbicyclo[2.2.2]oct-5-en-2-one 2, a versatile starting material for the 2-step synthesis of both symmetrical, such as Hayashi's Ph-bod* ligand, as well as novel unsymmetrical chiral dienes.

Chiral amines are ubiquitous in natural products and drugs, and their synthesis by asymmetric hydrogenation of carbonnitrogen double bonds has attracted much attention.[1] However, the search for and development of efficient catalysts for enantioselective C-N double bond hydrogenations with high enantioselectivity at a reasonable catalyst loading proved much more difficult than for the reduction of C = C and C = O groups. [2][3][4][5] Furthermore, most of those catalysts are only suitable for asymmetric hydrogenations of cyclic substrates, whereas acyclic imines still represent challenging compounds. [6] In this case, one of the major problems for achieving a high enantiomeric excess is the equilibrium between the E and Z isomer of the imine, [7] which makes it difficult for the catalyst to convert all stereoisomers in a uniform and selective manner. Consequently, the first successful chiral catalysts for this important transformation have only recently been described. Among them, homogenous Ir complexes with chiral P,P-or P,N-ligands, which are structurally analogous to Crabtrees catalyst, [8] have attracted particular attention. For example, Zhang and co-workers reported enantioselective hydrogenations of N-aryl imines (with up to > 99 % ee) by applying an iridium catalyst bearing a chiral 1,1'-bisphosphanylferrocene (f-binaphane).[9] Phosphanyloxazoline complexes with noncoordinating anions have been used by several group to afford products with up to 90 % ee. [10] Industrially relevant in this context is the asymmetric hydrogenation of an acyclic N-aryl imine as key step in the synthesis of the herbicide (S)-metolachlor by Syngenta.[11] Although only moderate enantioselectivities are achieved, the exceptionally high turnover numbers (TON) and turnover frequencies (TOF) of the iridium-ferrocenylphosphine catalyst allowed this imine reduction to become one of the largest catalytic enantioselective industrial processes to date. Chiral sulfoximines are versatile ligands for asymmetric catalysis, [12] and highly enantioselective hetero-Diels-Alder reactions, [13] Mukaiyama-type aldol, [14] and carbonyl-ene reactions [15] with sulfoximine-based catalysts have recently been described. In all these catalytic reactions, dinitrogen chelates such as 1 or 2 with sulfoximine units linked to quinoline or aniline moieties were applied. We thus focused our attention on the synthesis and use of phosphine-substituted sulfoximines 3, which on the basis of conclusions from solution and solid-state studies [13c, 16] were expected to be good metal binders through their P and N donor sites.For the preparation of diphenylphosphanyl sulfoximines 3, phosphine oxide 4, which can be obtained by palladiumcatalyzed cross-coupling of 2-bromo-1-iodobenzene with diphenylphosphane, served as starting material.[17] Application of the newly developed copper-mediated N-arylation reaction [18] afforded products 6 a-f from 4 and sulfoximines 5 a-f, respectively, in moderate to good yields (Scheme 1). Reductive deoxygenation of 6 with trichlorosil...

[reaction: see text] A simple and mild copper salt-catalyzed N-arylation of sulfoximines in high yields is reported. Cu(OAc)(2) activates aryl boronic acids for the reaction with NH-sulfoximines without additional base or heating. Furthermore, this new method allows the preparation of N-arylated sulfoximines, which have previously been more difficult to access.

Chiral amines are ubiquitous in natural products and drugs, and their synthesis by asymmetric hydrogenation of carbonnitrogen double bonds has attracted much attention.[1] However, the search for and development of efficient catalysts for enantioselective C-N double bond hydrogenations with high enantioselectivity at a reasonable catalyst loading proved much more difficult than for the reduction of C = C and C = O groups. [2][3][4][5] Furthermore, most of those catalysts are only suitable for asymmetric hydrogenations of cyclic substrates, whereas acyclic imines still represent challenging compounds. [6] In this case, one of the major problems for achieving a high enantiomeric excess is the equilibrium between the E and Z isomer of the imine, [7] which makes it difficult for the catalyst to convert all stereoisomers in a uniform and selective manner. Consequently, the first successful chiral catalysts for this important transformation have only recently been described. Among them, homogenous Ir complexes with chiral P,P-or P,N-ligands, which are structurally analogous to Crabtrees catalyst, [8] have attracted particular attention. For example, Zhang and co-workers reported enantioselective hydrogenations of N-aryl imines (with up to > 99 % ee) by applying an iridium catalyst bearing a chiral 1,1'-bisphosphanylferrocene (f-binaphane).[9] Phosphanyloxazoline complexes with noncoordinating anions have been used by several group to afford products with up to 90 % ee. [10] Industrially relevant in this context is the asymmetric hydrogenation of an acyclic N-aryl imine as key step in the synthesis of the herbicide (S)-metolachlor by Syngenta.[11] Although only moderate enantioselectivities are achieved, the exceptionally high turnover numbers (TON) and turnover frequencies (TOF) of the iridium-ferrocenylphosphine catalyst allowed this imine reduction to become one of the largest catalytic enantioselective industrial processes to date. Chiral sulfoximines are versatile ligands for asymmetric catalysis, [12] and highly enantioselective hetero-Diels-Alder reactions, [13] Mukaiyama-type aldol, [14] and carbonyl-ene reactions [15] with sulfoximine-based catalysts have recently been described. In all these catalytic reactions, dinitrogen chelates such as 1 or 2 with sulfoximine units linked to quinoline or aniline moieties were applied. We thus focused our attention on the synthesis and use of phosphine-substituted sulfoximines 3, which on the basis of conclusions from solution and solid-state studies [13c, 16] were expected to be good metal binders through their P and N donor sites.For the preparation of diphenylphosphanyl sulfoximines 3, phosphine oxide 4, which can be obtained by palladiumcatalyzed cross-coupling of 2-bromo-1-iodobenzene with diphenylphosphane, served as starting material.[17] Application of the newly developed copper-mediated N-arylation reaction [18] afforded products 6 a-f from 4 and sulfoximines 5 a-f, respectively, in moderate to good yields (Scheme 1). Reductive deoxygenation of 6 with trichlorosil...