Optically Active Arsenic Macrocycles. Highly Stereoselective Syntheses of Diastereomers and Enantiomers of 14-Membered Macrocyclic Dimers of (±)-2,3-Dihydro- and (±)-2,3,4,5-Tetrahydro-1-methyl-1,4-benzazarsepine

Abstract

The 14-membered trans-As2N2 macrocycle (9R*,18S*)-7,8,9,16,17,18-hexahydro-9,18-dimethyldibenzo[e,l]-[1,8,4,1l]diazadiarsacyclotetradecine [(R*,S*)-1] is formed with complete stereoselectivity when (±)-1,3-dimethyl-2-[2-[methyl(2-aminoethyl)arsino]phenyl]imidazolidine [(±)-3] is heated at 80 °C in vacuo. The achiral macrocycle quantitatively rearranges into seven-membered (±)-2,3-dihydro-1-methyl-4,1-benzazarsepine [(±)-5] in the presence of acid, although the monoimine spontaneously and stereoselectively dimerizes into (R*,S*)-1 when heated. Resolution of (±)-2-[methyl(2-aminoethyl)arsino]benzenemethanol [(±)-4] on [(R)-1-[1-(dimethylamino)ethyl]-2-naphthalenyl-C2, N]palladium(II) [[(R)-1-C10H6CH(Me)NMe2-C2, N]Pd+] followed by oxidation of the less soluble diastereomer (RAs, R)-17-Me2CH(OH) with BaMnO4, affords yellow distorted square-planar [[(R)-C10H6CH(Me)NMe2-C2, N]Pd{(S,S)-1-As,N}]PF6,[(RAs,SAs,R)-20] or orange trigonal-bipyramidal [(R)-C10H6CH(Me)NMe2-C2, N]Pd{Pd{S,S-As,As,N}]PF6·0.5Me2CO [(SAs,SAs,R)-20·0.5Me2CO], depending upon the solvents used for recrystallization. Resolving agent with (R*,S*)·1 in the presence of trifluoroacetic acid yields the same complexes after treatment of the reaction mixture with ammonium hexafluorophosphate. The yellow form of the complex crystallizes in the orthorhombic space group P212121(No.19) with a = 12.235 (5) Å, b = 15.176 (3) Å, c = 19.379 (3) Å, and Z = 4; the orange form crystallizes in the same space group with a = 18.358 (3) Å, b = 18.392 (3) Å, c = 11.927 (3) Å, and Z = 4. Optically pure macrocycle (R,R)-1, [α]D-99.8° (CH2Cl2), is displaced from either form of the diastereomers by chelating bis(tertiary phosphines). The mixing together of equimolar solutions of the mirror-image enantiomers of the diimine macrocycle in dichloromethane leads to the spontaneous crystallization of (R*,S*)-1 in a second-order asymmetric transformation involving monoimine (±)-5. Thus, racemic macrocycle (R*,R*)-1 cannot be isolated. Lithium aluminum hydride reductions of the various forms of 1 produce the corresponding macrocyclic diamines, viz., (R*,S*)-2, (R,R)-2, and (S,S)-2. The optically active forms of the diamine crystallize from chloroform as dichloroform solvates, [α]D±190° (CH2C12). Treatment of the macrocyclic diimines with acid prior to reduction affords the racemic and optically active forms of (±)-2,3,4,5-tetra-hydro-1-methyl-4,1-benzazarsepine [(±)-6]. The racemic diamine macrocycle (R*,R*)-2 was obtained by asymmetric transformation of (R*,S*)-2 on palladium(II). Thus, [Pd{(R*,S*)-2}]X2(X = Cl, PF6) upon being heated in water or dimethyl sulfoxide is quantitatively transformed into [Pd((R*,R*)-2)]X2, as demonstrated by recovery of pure (R*,R*)-2 from the rearranged complex. Apart from (R*,R*)-2, which is an oil, all forms of the macrocycles are air-stable crystalline solids. The macrocycles have excellent prospects as ligands for the stereospecific chelation of “soft” metals. Show more