Rapid assembly of heterocycle grafted macrocycles via tandem one-pot double 1,3-dipolar cycloaddition reaction.

Synthesis of triazole linked macrocycles grafted with glycospiroheterocycle was accomplished by stereo- and regioselective tandem double 1,3-dipolar cycloaddition (1,3-DC) reaction. By this method we could construct complex chiral macrocycles in good yields from the easily available starting materials and we could achieve the synthesis of two heterocyclic rings involving simultaneous formation of five bonds in one-pot reaction. The structures of the macrocycles were confirmed by spectroscopic methods and single crystal XRD.

Methyl (2Z)-2-[(2-formyl-3-methyl-1H-indol-1-yl)meth-yl]-3-(4-meth-oxy-phen-yl)prop-2-enoate.

In the title indole derivative, C22H21NO4, the dihedral angle between the benzene and pyrrole rings of indole moiety is 1.8 (1)°. The plane of the 4-meth-oxy-phenyl ring is oriented with a dihedral angle of 60.7 (1)° with respect to the plane of the indole moiety. The mol-ecular packing is stabilized by C-H⋯O hydrogen bonds which form a V-shaped chain arrangement along the bc plane of the unit cell. In addition to this, C-H⋯π and π-π inter-actions [centroid-centroid distances = 3.8102 (11) and 3.8803(12) Å], which run along the b-axis direction, stabilize the mol-ecular packing.

6a-Nitro-6-(2,2,7,7-tetra-methyl-tetra-hydro-3aH-bis-[1,3]dioxolo[4,5-b:4',5'-d]pyran-5-yl)-6a,6b,7,8,9,11a-hexa-hydro-6H-spiro-[chromeno[3,4-a]pyrrolizine-11,11'-indeno-[1,2-b]quinoxaline].

In the title compound, C39H38N4O8, the quinoxaline and indene subunits are essentially planar, with maximum deviations of 0.071 (2) and 0.009 (2) Å, respectively. The indeno-quinoxaline system forms a dihedral angle of 72.81 (3)° with the chromenopyrrolizine system. The two dioxolane rings, as well as the pyran ring of the chromeno group and the terminal pyrrolizine, each adopt an envelope conformation with O and C as flap atoms. The central pyrrolizine ring adopts a twisted conformation. Intra-molecular C-H⋯O and C-H⋯N hydrogen bonds occur. The crystal structure exhibits C-H⋯O hydrogen bonds, and is further stablized by C-H⋯π inter-actions, forming a two-dimensional network along the bc plane.

Crystal structures of methyl 3-phenyl-4,5-di-hydro-1H,3H-benzo[4,5]imidazo[2,1-c][1,4]oxazepine-4-carboxyl-ate and methyl 1-methyl-3-phenyl-4,5-di-hydro-1H,3H-benzo[4,5]imidazo[2,1-c][1,4]oxazepine-4-carboxyl-ate.

The title compounds, C19H18N2O3, (I), and C20H20N2O3, (II), differ only by a methyl substituent on the seven-membered oxazepine ring in (II). In both compounds, these rings have a twist-chair conformation. The phenyl ring makes a dihedral angle of 73.42 (10)° with the benzimidazole ring system mean plane (r.m.s. deviation = 0.015 Å) in (I) and 83.07 (7)° in (II) (r.m.s. deviation = 0.026 Å). The methyl carboxyl-ate groups are planar to within 0.031 (2) in (I) and 0.003 (2) Šin (II). They are inclined to the phenyl and benzimidazole ring system by 33.78 (16) and 87.56 (14)°, respectively, in (I) and by 53.04 (12) and 60.22 (11)°, respectively, in (II). In the crystal of (I), mol-ecules stack in a herringbone fashion and are linked by C-H⋯O hydrogen bonds, forming chains along [100]. In the crystal of (II), there are no significant inter-molecular inter-actions present.

Crystal structures of ethyl (2S*,2'R*)-1'-methyl-2'',3-dioxo-2,3-di-hydro-dispiro-[1-benzo-thio-phene-2,3'-pyrrolidine-2',3''-indoline]-4'-carboxyl-ate and ethyl (2S*,2'R*)-5''-chloro-1'-methyl-2'',3-dioxo-2,3-di-hydro-dispiro-[1-benzo-thio-phene-2,3'-pyrrolidine-2',3''-indoline]-4'-carboxyl-ate.

In the title compounds, C22H20N2O4S, (I), and C22H19ClN2O4S, (II), the pyrrolidine rings have twist conformations on the spiro-spiro C-C bonds. In (I), the five-membered ring of the oxindole moiety has an envelope conformation with the spiro C atom as the flap, while in (II) this ring is flat (r.m.s. deviation = 0.042 Å). The mean planes of the pyrrolidine rings are inclined to the mean planes of the indole units [r.m.s deviations = 0.073 and 0.069 Šfor (I) and (II), respectively] and the benzo-thio-phene ring systems (r.m.s. deviations = 0.019 and 0.034 Šfor (I) and (II), respectively) by 79.57 (8) and 88.61 (7)° for (I), and by 81.99 (10) and 88.79 (10)° for (II). In both compounds, the eth-oxy-carbonyl group occupies an equatorial position with an extended conformation. The overall conformation of the two mol-ecules differs in the angle of inclination of the indole unit with respect to the benzo-thio-phene ring system, with a dihedral angle between the planes of 71.59 (5) in (I) and 82.27 (7)° in (II). In the crystal of (I), mol-ecules are linked via pairs of N-H⋯O hydrogen bonds, forming inversion dimers enclosing R 2 (2)(14) loops. The dimers are linked via C-H⋯O and bifurcated C-H⋯O(O) hydrogen bonds, forming sheets lying parallel to (100). In the crystal of (II), mol-ecules are again linked via pairs of N-H⋯O hydrogen bonds, forming inversion dimers but enclosing smaller R 2 (2)(8) loops. Here, the dimers are linked by C-H⋯O hydrogen bonds, forming ribbons propagating along [010].

Methyl 9-(4-meth-oxy-phen-yl)-19-methyl-3,12-di-aza-penta-cyclo-[10.7.0.0(2,10).0(3,8).0(13,18)]nona-deca-1(19),13(18),14,16-tetra-ene-10-carboxyl-ate.

The title ester, C27H30N2O3, crystallizes with two independent mol-ecules in the asymmetric unit whose geometrical features are similar. In each mol-ecule, the pyrrolidine ring adopts an envelope conformation, with the fused C atom shared with the piperidine ring as the flap, and the piperidine ring adopts a chair conformation. In the crystal, C-H⋯π inter-actions link the inversion-related molecules and form a dimeric arrangement in the unit cell.

2-[(Ferrocen-1-yl)(hy-droxy)meth-yl]prop-2-ene-nitrile.

In the title ferrocene derivative, [Fe(C5H5)(C9H8NO)], the dihedral angle between the ene-nitrile group and the substituted cyclo-penta-dienyl ring is 71.2 (1)°. The cyclopentadienyl rings of the ferrocene moiety are arranged in an eclipsed conformation. The hy-droxy group, and the corresponding methine H atom, are disordered over two sets of sites with site-occupancy factors of 0.744 (4) and 0.256 (4). An intra-molecular C-H⋯O close contact is observed. In the crystal, O-H⋯N hydrogen bonds form a C(6) chain along [100].

Ethyl 1'-methyl-2-oxo-4'-[(3aR,5R,5aS,8aS,8bR)-2,2,7,7-tetra-methyl-tetra-hydro-3aH-bis-[1,3]dioxolo[4,5-b:4',5'-d]pyran-5-yl]-2H-spiro-[ace-naphthyl-ene-1,2'-pyrrolidine]-3'-carboxyl-ate.

In the title mol-ecule, C30H35NO8, the ace-naphthyl-enone moiety, two atoms of a methyl pyrrolidine ring (N and C atoms) and four atoms of an ethyl acetate moiety (two C and two O atoms) are disordered over two sets of sites in ratio 0.532 (7):0.468 (7). The three C atoms of a di-meth-oxy-ethane ring and dioxolane ring attached with two methyl groups are disordered over two sets of sites in 0.66 (2):0.34 (2) and 0.62 (2):0.38 (2) ratios, respectively. The major and minor components of the ace-naphthyl-ene ring are essentially planar (r.m.s. deviations = 0.0254 and 0.0436 Å, respectively). The major and minor components of the pyrrolidine ring adopt C-envelope conformations with C atoms displaced by 0.492 (11) and 0.595 (7) Šfrom the remaining ring atoms. One of the dioxolane rings is disordered with its major component in an envelope conformation [C displaced by 0.511 (11) Å] and the minor fraction is more or less planar with an r.m.s. deviation of 0.070 Å. The other dioxolane ring is in an envelope conformation, with a C atom displaced by 0.438 (3) Šfrom the remainder of the ring atoms. The crystal packing features C-H⋯O inter-actions, which generate C(9) chains.

(1S,1'S,2'R,4a'S,9a'S,9b'R)-1'-Acet-yloxy-2,4'-dioxo-2',4',4a',7',8',9',9a',9b'-octa-hydro-1'H,2H-spiro-[ace-naphthyl-ene-1,5'-pyrano[4,3-a]pyrrolizin]-2'-ylmethyl acetate.

In the title compound C26H25NO7, the mean plane through the lactone-substituted ring of the pyrrolizidine moiety forms dihedral angles of 78.46 (6) and 58.28 (8)° with the ace-naphthyl-ene moiety and the sugar based-lactone ring, respectively. The sum of the angles at the the N atom of the pyrrolizidine ring (335.0°) is in accordance with sp (3) hybridization. Some atoms of the acetate group are disordered and were refined using a split model [occupancy ratio 0.673 (10):0.327 (10)].

(4'-Acet-yloxy-1,3,1'-trioxo-1,3,4,4a,4b,5,6,7,9,9a-deca-hydro-spiro-[indene-2,9'-pyrano[4,3-a]pyrrolizin]-3'-yl)methyl acetate.

In the title compound, C23H23NO8, the dihedral angle between the five- and six-membered rings of the indene-dione moiety is 3.09 (13)°. The mean plane of the five-membered ring (which has a flat envelope conformation with the spiro C atom as the flap) is inclined to the mean plane of the central five-membered ring of the pyrrolizine unit by 76.48 (12)°. This central ring has a twist conformation on the N-C(spiro) bond. The outer ring of the pyrrolizine unit has an envelope conformation with the N atom as the flap. The mean planes of these two fused rings are inclined to one another by 65.28 (15)°. The pyran ring has a screw-boat conformation and its mean plane makes a dihedral angle of 29.50 (11)° with the mean plane of the central five-membered ring of the pyrrolizine unit. In the crystal, mol-ecules are linked via C-H⋯O hydrogen bonds, forming two-dimensional networks lying parallel to the ab plane.

(1'S,12'R,13'S,17'S)-15',15'-Dimethyl-1,2-dihydro-11',14',16',18'-tetra-oxa-7'-aza-spiro-[indole-3,8'-penta-cyclo-[10.6.0.0(2,9).0(3,7).0(13,17)]octa-deca-ne]-2,10'-dione.

In the title compound, C22H24N2O6, the indole ring has a twist conformation and the tetra-hydro-2H-pyran-2-one ring a half-chair conformation. One of the pyrrolidine rings adopts an envelope conformation on the N atom, while the other has a twist conformation; the 'butterfly' angle between their mean planes is 62.98 (11)°. The dioxolane ring adopts a twist conformation and the tetra-hydro-furan ring has an envelope conformation on the C atom in the fused tetra-hydro-2H-pyran-2-one ring adjacent to the O atom of the tetra-hydro-furan ring. The 'butterfly' angle between the mean planes of these two five-membered rings is 69.14 (10)°. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds, forming chains along the a axis.

Methyl 11-hy-droxy-9-[1-(4-meth-oxy-phen-yl)-4-oxo-3-phen-oxy-azetidin-2-yl]-18-oxo-10-oxa-2-aza-penta-cyclo-[9.7.0.0(1,8).0(2,6).0(12,17)]octa-deca-12(17),13,15-triene-8-carboxyl-ate.

In the title compound, C(34)H(32)N(2)O(8), one of the pyrrolidine rings in the pyrrolizidine ring system adopts a twist conformation, whereas the other ring adopts an envelope conformation (C atom as flap). The five-membered ring in the indene ring system and the fused furan ring also adopt envelope conformations (C and O atoms as flaps, respectively). The ß-lactam ring makes dihedral angles of 23.41 (2) and 25.98 (2)°, respectively, with the attached meth-oxy-phenyl and phen-oxy rings. The mol-ecular conformation is stabilized by an intra-molecular O-H⋯N hydrogen bond, generating an S(5) motif. In the crystal, mol-ecules are linked into C(12) chains running along the a axis by C-H⋯O hydrogen bonds. The structure is further consolidated by weak inter-molecular C-H⋯π and π-π inter-actions [centroid-centroid distance = 3.7987 (14) Å].

11-[1-(4-Meth-oxy-phen-yl)-4-oxo-3-phen-oxy-azetidin-2-yl]-14-methyl-12-oxa-8,14-diaza-tetra-cyclo-[8.3.3.0(1,10).0(2,7)]hexa-deca-2(7),3,5-triene-9,13-dione.

In the title compound, C(30)H(27)N(3)O(6), the furan and pyrrolidine rings adopt envelope conformations (with C and N atoms as the flaps, respectively). The piperidine ring is in a distorted boat conformation. The ß-lactam ring is planar [maximum deviation = 0.0044 (16) Å] and forms dihedral angles of 30.61 (9) and 85.51 (9)°, respectively, with the attached meth-oxy-phenyl and phen-oxy rings. The crystal packing is stabilized by N-H⋯O and C-H⋯O inter-actions forming R(2) (2)(8), R(2) (2)(20) and R(2) (2)(14) ring motifs. The crystal structure is further consolidated by weak C-H⋯π inter-actions.

Ethyl 7'-(6-benz-yloxy-2,2-dimethyl-tetra-hydro-furo[3,2-d][1,3]dioxol-5-yl)-2-oxo-5',6',7',7a'-tetra-hydro-1'H,2H-spiro-[acenaphthyl-ene-1,5'-pyrrolo-[1,2-c][1,3]thia-zole]-6'-carboxyl-ate.

In the title compound, C(34)H(35)NO(7)S, the acenaphthyl-ene unit is essentially planar (r.m.s. deviation = 0.0335 Å). The pyrrolo-thia-zole ring system is folded about the bridging N-C bond; the thia-zolidine and pyrrolidine rings adopt S- and C-envelope conformations, respectively, with a 'butterfly' angle between the mean planes of 51.38 (10)°. The dioxolane and tetra-hydro-furan rings adopt O- and a C-envelope conformations, respectively, with a 'butterfly' angle between the mean planes of 57.12 (10)°. Two C atoms are each disordered over two positions with site-occupancy factors of 0.450 (7) and 0.550 (7). The crystal packing is stabilized by C-H⋯O inter-actions, generating an R(2) (2)(14) graph-set ring motif.

Ethyl (1R,1'S,2'S,7a'R)-2-oxo-1'-[(3aR,5R,5aS,8aS,8bR)-2,2,7,7-tetra-methyl-tetra-hydro-3aH-bis-[1,3]dioxolo[4,5-b:4',5'-d]pyran-5-yl]-1',2',5',6',7',7a'-hexa-hydro-2H-spiro-[acenaphthyl-ene-1,3'-pyrrolizine]-2'-carboxyl-ate.

In the title compound, C(32)H(37)NO(8), the central pyran ring adopts a twist-boat conformation and the 1,3-dioxoane rings adopt envelope conformations. The acenaphthyl-enone unit and two C atoms of a pyrrolidine ring are disordered over two sets of sites [occupancy ratio 0.669 (7):0.331 (7)]. The major fraction of the disordered pyrrolidine ring exhibits an envelope conformation while the minor component is essentially planar [maximum deviation = 0.037 (12) Å]. The other pyrrolidine ring also adopts an envelope conformation. The dihedral angle between the mean planes of the two wings of the pyrrolidine ring is 30.6 (2)°. Both the major and minor components of the acenaphthyl-enone unit are essentially planar, the maximum deviations being 0.025 (10) and 0.047 (19) Å, respectively; the dihedral angle between the mean planes of the two components is 1.72 (3)°. The crystal packing features C-H⋯O inter-actions.

1-(2-Hy-droxy-eth-yl)-1'-methyl-4'-(naph-thal-en-1-yl)-1'',2'',3'',4''-tetra-hydro-dispiro-[indoline-3,2'-pyrrolidine-3',2''-naphthalene]-2,1''-dione.

In the title compound, C(33)H(30)N(2)O(3), the pyrrolidine ring adopts an envelope conformation in which the H atom attached the an ortho-C atom deviates from the plane, whereas the cyclo-hexa-none ring in the tetra-hydro-naphthalene fused-ring system adopts a sofa conformation. The oxindoline ring system is almost perpendicular with respect to the mean plane of the pyrrolidine ring, with a dihedral angle of 89.0 (1)°. Five intra-molecular C-H⋯O close contacts are observed. In the crystal, mol-ecules associate via O-H⋯O hydrogen bonds, forming R(2) (2)(14) dimers. In addition, there are weak C-H⋯π inter-actions.

{1'-Phenyl-1',2',5',6',7',7a'-hexa-hydro-spiro-[indeno-[1,2-b]quinoxaline-11,3'-pyrrolizin]-2'-yl}(p-tol-yl)methanone.

In the title compound, C(35)H(29)N(3)O, the quinoxaline and indene systems are essentially planar, with maximum deviations of 0.047 (2) and 0.032 (2) Šfor C atoms, respectively. The quinoxaline system forms a dihedral angle of 4.75 (3)° with the indene system. The pyrrolizine system is folded. The substituted five-membered ring adopts an envelope conformation. In the other five-membered ring, one C atom is disordered with a site-occupancy ratio of 0.676 (12):0.324 (12). In the crystal, mol-ecules are linked via C-H⋯O hydrogen bonds involving the bifurcated carbonyl O atom.

3-(Ferrocen-1-ylcarbon-yl)-1-methyl-4-(4-methyl-phen-yl)spiro-[pyrrolidine-2,11'-indeno-[1,2-b]quinoxaline].

In the title compound, [Fe(C(5)H(5))(C(32)H(26)N(3)O)], the pyrrolidine ring adopts a twist conformation. The indeno-quinoxaline ring system [86.44 (5)°], the methyl-phenyl ring [86.06 (7)°] and the ferrocene rings [82.00 (7) and 83.95 (9)°] are almost perpendicular to the pyrrolidine ring. The two cyclopentadienyl rings adopt an eclipsed conformation. The crystal structure features C-H⋯N inter-actions.

4-Ferrocenyl-1-methyl-3-benzoyl-spiro-[pyrrolidine-2,11'-indeno-[1,2-b]quinoxaline].

In the title compound, [Fe(C5H5)(C31H24N3O)], the pyrrolidine ring adopts a twist conformation. The pyrrolidine ring is almost perpendicular to the indeno-quinoxaline ring system, making a dihedral angle of 84.44 (5)°. The cyclo-penta-dienyl rings of the ferrocene moiety adopt an eclipsed conformation. The crystal packing features weak C-H⋯N and C-H⋯π inter-actions.

3'-Ferrocenylcarbon-yl-1'-methyl-4'-phenyl-spiro-[indeno-[2,3-b]quinoxaline-11,2'-pyrrolidine].

In the title compound, [Fe(C(5)H(5))(C(31)H(24)N(3)O)], the pyrrolidine ring makes a dihedral angle of 86.3 (3)° with the mean plane [r.m.s deviation = 0.074 (2) Å] of the indeno-quinoxaline ring system. The central pyrrolidine ring adopts a twist conformation and the two cyclopentadienyl rings adopt an eclipsed conformation. In the crystal, mol-ecules are linked by weak C-H⋯N and C-H⋯π inter-actions, propagating along the c and a axes, respectively.