Ethyl 2,6-bis(4-bromophenyl)-1-isocyano-4-oxocyclohexanecarboxylate

In the title compound, C22H19Br2NO3, the central oxocyclohexane ring is in a twist-boat conformation; all the substituents (one ethoxycarbonyl and two aryl groups) are located in equatorial orientations. One of the –CH2– groups and the opposite –CH– group bearing a bromobenzene substituent form the flagpoles of the twist-boat. The dihedral angle between the aromatic rings is 76.4 (4)°. In the crystal, weak C—H⋯O interactions link the molecules into C(5) chains propagating in the [010] direction. A short Br⋯O contact of 3.254 (4) Å is observed.

Financial support of this research by the Science and Technology Development Program Foundation of Jilin Province (No. 20140204022NY), the Interdisciplinary Innovation Fund of Jilin University (No. 450060481143) and the PhD Fund of Jilin University (No. 20140402) is gratefully acknowledged Supporting information for this paper is available from the IUCr electronic archives (Reference: HB7238).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 1.
Hydrogen atoms were generated in idealized positions (according to the sp2 or sp3 geometries of their parent carbon), and then refined using a riding model with fixed C-H distances (C-H = 0.95-1.00 Å) and with Uiso(H) = 1.2Ueq(C).

Comment
In the process of strategies developing of [5+1] annulation for the construction of six-membered cyclic compounds, we have found that ethyl isocyanoacetate is an active carbon nucleophile that can react with divinyl ketone through a tandem double Michael-addition cyclization. This one-step annulation can regiospecificly forms highly constrained cyclohexane analogues of phenylanaline (Phe) which are precursors for the synthesis of peptide analogues with controlled fold in the backbone. The constrained ring systems play important roles in restricting torsional angle χ1 and in peptide receptor recognition processes, thus the [5+1] annulation reactions have drew much attentions and both the five-carbon 1,5bielectrophiles and the one-atom nucleophiles been explored extensively Dong et al., 2005;Hu et al., 2008;Zhao et al., 2006;Fu et al., 2009;Xu et al., 2012).
The title compound, a phenyl substituted highly constrained cyclohexane analogue of Phe, is one of the products obtained during the study of [5+1] annulation of divinyl ketone and isocyanoacetate. In the crystal, the central sixmember oxocyclohexane ring adopts a twist-boat conformation (Fig. 1), and all of the ethoxyl carbonyl and two aryl groups are located in equatorial positions. The aryl groups are trans to each other and the dihedral angle between two supporting information aromatic rings is 76.45 (4) °. In this molecular, C11 with axial hydrogen and C8 (CH 2 ) are on the flagpole positions of the boat conformation, which give the least torsional strain. C12 and C7 are on one side of the boat conformation, and their equatorial substituents, ethoxyl carbonyl and aryl groups, fit in with the formation boat conformation of this compound.

Figure 1
View of the molecular structure of the title compound with displacement ellipsoids drawn at the 30% probability level. Hydrogen site location: inferred from neighbouring sites H-atom parameters constrained w = 1/[σ 2 (F o 2 ) + (0.0466P) 2 + 7.9699P]

Ethyl 2,6-bis(4-bromophenyl)-1-isocyano-4-oxocyclohexanecarboxylate
where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.001 Δρ max = 1.11 e Å −3 Δρ min = −0.92 e Å −3 Special details Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.