A new approach to alkaloid-like systems: synthesis and crystal structure of 1-(2-acetyl-11-methoxy-5,6-dihydro[1,3]dioxolo[4,5-g]pyrrolo[2,1-a]isoquinolin-1-yl)propan-2-one

1-(2-Acetyl-11-methoxy-5,6-dihydro[1,3]dioxolo[4,5-g]pyrrolo[2,1-a]isoquinolin-1-yl)propan-2-one, the product of a domino reaction between cotarnine chloride and acetylacetylene catalysed by copper(I) iodide, was studied by X-ray diffraction.

The title compound, C 19 H 19 NO 5 , (I), is the product of a domino reaction between cotarnine chloride and acetylacetylene catalysed by copper(I) iodide. The molecule of (I) comprises a fused tetracyclic system containing two terminal five-membered rings (pyrrole and 1,3-dioxole) and two central six-membered rings (dihydropyridine and benzene). The five-membered 1,3-dioxole ring has an envelope conformation and the central six-membered dihydropyridine ring adopts a twist-boat conformation. The acyl substituent is almost coplanar with the pyrrole ring, whereas the methoxy substituent is twisted by 27.93 (16) relative to the benzene ring. The 2-oxopropan-1-yl substituent is roughly perpendicular to the pyrrole ring. In the crystal, molecules are stacked along the a-axis direction; the stacks are linked by weak C-HÁ Á ÁO hydrogen bonds into puckered layers lying parallel to (001).

Chemical context
The 5,6-dihydropyrrolo[2,1-a]isoquinoline fragment is included in several natural products, for example in lamellarin I and K alkaloids, which possess a variety of biological properties, in particular, antitumor activity (Komatsubara et al., 2014;Imperatore et al., 2014).
It is of fundamental importance for the preparation of 2,3bifunctional substituted pyrrolo[2,1-a]isoquinolines to study the interaction of iminium salts with activated alkynes. In this work, we modified the approach to the synthesis of alkaloidlike compounds by the reaction of cotarnine chloride with activated alkynes in the presence of copper halogenides as a catalyst. The synthetic method proposed is new and original. This process includes the formation of the pyrrole ring and its functionalization, which is necessary for the chemical diversity of pyrroloisoquinoline systems.
The title compound (I) is a product of a new domino reaction between cotarnine chloride and acetylacetylene catalysed by copper(I) iodide. The reaction sequence starts with nucleophilic addition of copper(I) acetylide to cotarnine chloride followed by [2,3]-cycloaddition and aromatization of the pyrrole ring . The main speciality of the reaction is the conversion of the acetylethynyl fragment to acetylmethyl when the pyrrole ring is formed in an aprotic solvent. The structure of the product (I) was unambiguously established by an X-ray diffraction study.

Structural commentary
The molecule of (I), representing a new alkaloid-like skeleton, comprises a fused tetracyclic system containing two terminal five-membered rings (pyrrole and 1,3-dioxole) and two central six-membered rings (dihydropyridine and benzene) (Fig. 1). The five-membered 1,3-dioxole ring has its usual shallow envelope conformation, with the methylene group as the flap, and the central six-membered dihydropyridine ring adopts a twist-boat conformation. The dihedral angle between the pyrrole and benzene rings is 29.69 (3) . The nitrogen N4 atom is essentially planar (sum of bond angles = 359.73 ). The acyl substituent is almost coplanar with the pyrrole ring (r.m.s. deviation for non-hydrogen atoms = 0.012 Å ), whereas the methoxy substituent is twisted by 27.93 (16) relative to the benzene ring. The propan-2-one-1-yl substituent is roughly perpendicular to the pyrrole ring, the dihedral angle being 76.81 (5) , because of steric reasons.

Supramolecular features
The crystal packing of molecules of (I) involves stacking along the a-axis direction (Fig. 2), with molecules linked by weak C-HÁ Á ÁO hydrogen bonds into puckered layers lying parallel to (001) ( Table 1, Fig. 2).

Figure 2
Crystal structure of (I) illustrating the hydrogen-bonded layers parallel to

Synthesis and crystallization
Acetylacetylene (0.27 g, 3.9 mmol) was added to a stirred suspension of cotarnine chloride (0.10 g, 0.39 mmol) and CuI (0.011 g, 0.059 mmol) in CH 2 Cl 2 (10 ml) under Ar at 256 K ( Fig. 3). After stirring at 256 K for 1 h, triethylamine (0.059 g, 0.59 mmol) was added to the mixture under Ar at 256 K. The reaction mixture was stirred at 256 K for 30 min, and brought to room temperature and stirred for three days. The reaction progress was monitored by TLC (eluent EtOH). After the completion, the solvent was removed in vacuum, and the residue separated by column chromatography on silica gel (EtOAc-hexane, 1:1). After removing the solvent, the residue was recrystallized from an EtOAc-hexane solvent mixture to give 37 mg (28% yield) of yellow-orange crystals of the title compound, m.p. = 448-450 K (EtOAc-hexane).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. Hydrogen atoms were placed in calculated positions with C-H = 0.95-0.99 Å and refined using the riding model with fixed isotropic displacement parameters [U iso (H) = 1.5U eq (C) for the CH 3 -groups and 1.2U eq (C) for the other groups].

Funding information
The publication was prepared with the support of the RUDN University Program '5-100' and by the Russian  Synthesis of (I) using a domino reaction between cotarnine chloride and acetylacetylene catalysed by copper(I) iodide.

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.