(2aR*,5S*,6aS*,8aS*,E)-Ethyl 5-hy­droxy-7,7,8a-trimethyl-8-oxo-2,2a,6,6a,7,8,8a,8b-octa­hydro-1H-penta­leno[1,6-bc]oxepine-4-carboxyl­ate

Goverdhan Mehta; C S Ananda Kumar; Saikat Sen

doi:10.1107/S1600536812046776

. 2012 Nov 24;68(Pt 12):o3392–o3393. doi: 10.1107/S1600536812046776

(2aR,5S,6aS,8aS,E)-Ethyl 5-hydroxy-7,7,8a-trimethyl-8-oxo-2,2a,6,6a,7,8,8a,8b-octahydro-1H-pentaleno[1,6-bc]oxepine-4-carboxylate

Goverdhan Mehta ^a,^*,^‡, C S Ananda Kumar ^a, Saikat Sen ^a

PMCID: PMC3588985 PMID: 23476221

Abstract

The title compound, C₁₇H₂₄O₅, featuring a 2-carbethoxy-3-oxepanone unit in its intramolecularly O—H⋯O hydrogen-bonded enol form, was obtained via [(CF₃CO₂)₂Rh]₂-catalysed intramolecular O—H bond insertion in the α-diazo-ω-hydroxy-β-ketoester, ethyl 4-[(1S,3aS,6R,6aS)-6-hydroxy-2,2,3a-trimethyl-3-oxo-octahydropentalen-1-yl]-2-diazo-3-oxobutanoate. The seven-membered oxacyclic ring, thus constructed on a cis-fused diquinane platform, was found to adopt a distorted boat–sofa conformation.

Related literature

For rhodium carbenoid-mediated intermolecular O—H insertion reactions and their application to natural product synthesis, see: Paulissen et al. (1973 ▶); Cox et al. (1994 ▶); Haigh (1994 ▶); Aller et al. (1995 ▶); Shi et al. (1995 ▶); Bulugahapitiya et al. (1997 ▶); Moody & Miller (1998 ▶); Nelson et al. (2000 ▶); Medeiros & Wood (2010 ▶); Freeman et al. (2010 ▶); Morton et al. (2012 ▶). For rhodium-catalysed intramolecular O—H insertion reactions, see: Paulissen et al. (1974 ▶); Moyer et al. (1985 ▶); Moody & Taylor (1987 ▶); Heslin & Moody (1988 ▶); Davies et al. (1990 ▶); Moody et al. (1992 ▶); Sarabia-Garciá et al. (1994) ▶; Padwa & Sá (1999 ▶); Im et al. (2005 ▶). For reviews on rhodium-mediated C—H insertion reactions, see: Doyle et al. (2010 ▶); Davies & Morton (2011 ▶). For the construction of an angularly fused triquinane skeleton via Rh^II-catalysed intramolecular C—H insertion, see: Srikrishna et al. (2012 ▶). For the isolation and synthesis of penifulvin A, see: Shim et al. (2006 ▶); Gaich & Mulzer (2009 ▶); Mehta & Khan (2012 ▶). For the application of p-acetamidobenzenesulfonyl azide as a diazo transfer reagent, see: Baum et al. (1987 ▶). For ring conformations, see: Cremer & Pople (1975 ▶); Boessenkool & Boeyens (1980 ▶).

Experimental

Crystal data

C₁₇H₂₄O₅
M _r = 308.36
Orthorhombic,
a = 8.447 (5) Å
b = 18.454 (14) Å
c = 21.735 (15) Å
V = 3388 (4) Å³
Z = 8
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 291 K
0.20 × 0.18 × 0.08 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2003 ▶) T _min = 0.983, T _max = 0.993
14606 measured reflections
3153 independent reflections
1408 reflections with I > 2σ(I)
R _int = 0.087

Refinement

R[F ² > 2σ(F ²)] = 0.053
wR(F ²) = 0.149
S = 0.89
3153 reflections
207 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.17 e Å⁻³

Data collection: APEX2 (Bruker, 2007 ▶); cell refinement: SAINT (Bruker, 2007 ▶); data reduction: SAINT; program(s) used to solve structure: SIR92 (Altomare et al., 1994 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▶); software used to prepare material for publication: PLATON (Spek, 2009 ▶).

Supplementary Material

Click here for additional data file.^{(26.7KB, cif)}

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812046776/ds2220sup1.cif

e-68-o3392-sup1.cif^{(26.7KB, cif)}

Click here for additional data file.^{(151.6KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812046776/ds2220Isup2.hkl

e-68-o3392-Isup2.hkl^{(151.6KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2O⋯O4	0.93 (3)	1.69 (3)	2.565 (4)	155 (3)

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Acknowledgments

We thank the Department of Science and Technology (DST), India, for the CCD facility at the Indian Institute of Science (IISc), Bangalore. CSAK thanks the University Grants Commission for the award of a Dr D. S. Kothari post-doctoral fellowship. GM thanks the Government of India for the award of a National Research Professorship and acknowledges the current research support from the Eli Lilly and Jubilant–Bhartia Foundations.

supplementary crystallographic information

Comment

Rhodium carbenoid mediated O—H insertion provides a facile means of transforming diazo-compounds into diverse range of functionalized ethers (Paulissen, et al., 1973; Cox, et al. 1994; Haigh, 1994; Aller et al., 1995; Shi et al., 1995; Bulugahapitiya et al., 1997; Moody & Miller, 1998; Morton et al., 2012). Hence the methodology has proven to be a useful stratagem in the synthetic acquisition of several natural products (Nelson et al., 2000; Medeiros & Wood, 2010; Freeman, et al. 2010). While not as extensively utilized or studied as the intermolecular variants, intramolecular interception of rhodium carbenoids by hydroxy nucleophiles can, nevertheless, afford an effective route to cyclic ethers and lactones (Paulissen et al., 1974; Moyer et al., 1985; Moody & Taylor, 1987; Heslin & Moody, 1988; Moody et al. 1992; Sarabia-García et al., 1994; Padwa & Sá, 1999; Im et al., 2005). Indeed, studies by Moody and co-workers have shown that rhodium(II) acetate catalysed cyclization in diazoalcohols may even be employed as a practical method for accessing medium-ring oxacycles - oxepanes, in particular, wherein interference from competing C—H insertion reactions do not appear to be significant (Heslin & Moody, 1988; Davies et al., 1990).

Against this background, we report herein the crystal structure of the title compound 1, a 2-carbethoxy-3-oxepanone embedded in a tricyclic framework, that was obtained as the sole isolable product in the rhodium(II) trifluroacetate mediated decomposition of the α-diazo-ω-hydroxy-β-ketoester 2 (Figure 1). Originally envisaged as an entry point to an angularly fused triquinane skeleton via Rh(II) catalyzed intramolecular C—H insertion (Doyle et al., 2010; Davies & Morton, 2011; Srikrishna et al., 2012) en route to the natural product penifulvin A (Shim et al., 2006; Gaich & Mulzer, 2009; Mehta & Khan, 2012), the diazoester 2 was prepared from the β-ketoester 3via a diazo transfer reaction to the activated methylene group in 3 (Baum et al., 1987).

The crystal structure of 1 was solved and refined in the centrosymmetric orthorhombic space group Pbcn (Z = 8). The 2-carbethoxy-3-oxepanone moiety in 1 was found to exist in the intramolecularly O—H···O hydrogen bonded enol form (Figure 2). As indicated by its puckering parameters (q₂ = 0.915 (3) Å, q₃ = 0.310 (3) Å, φ₂ = 193.59 (17)°, φ₃ = 118.9 (5)°, Q_T = 0.967 (2) Å), the seven-membered oxacyclic ring adopted a distorted boat-sofa conformation (Cremer & Pople, 1975; Boessenkool & Boeyens, 1980). Crystal packing in 1 was effected primarily via the agency of weak van der Waals interactions, though short C—H···O contacts (C8—H8···O2) could be discerned among the molecules.

Experimental

As shown in Figure 1, the title compound 1 was prepared from the the β-ketoester 3via the intermediate diazoester 2. Thus, 3, upon treatment with p-acetamidobenzenesulfonyl azide and triethylamine, afforded 2. The α-diazo-ω-hydroxy-β-ketoester 2 underwent smooth cyclization in presence of catalytic rhodium(II) trifluoroacetate dimer to deliver the oxepanone 1, which crystallized as thin colorless plates from 1:1 dichloromethane-hexanes.