The pyrrolo[1,2-a]azocine backbone is contained as the CE subunit in the structures of manzamine and ircinal alkaloids (Rao et al., 2006), as well as other natural and synthetic compounds which have shown interesting biological properties (Yap et al., 2011; Sun et al., 2011). Among the methods for a rapid construction of bicycle alkaloid, domino processes promoted by catalytic decomposition of diazo compounds have become commonly employed since they give a rapid access to complex structures in a stereoselective way (Doyle et al., 1997; Clark et al., 2001).

The used route for the synthesis of the title compound is described in Figure 1. The diazocarbonyl derivative 1 was synthesized starting from L-proline and (–)-menthyl acetate. The decomposition in refluxing toluene with Cu(acac)₂ or Rh₂(OAc)₄ brought in one step to the pyrroloazocine alkaloid 3. The decomposition triggers a domino process that involved a carbenoidic attack to the nitrogen lone pair and the formation of the [5,5]-spirocyclic ammonium ylide 2. The ylide undergoes a [2,3]-sigmatropic rearrangement and it was possible to isolate the alkaloid 3 in 70% yield and 97% enantiomeric excess (Muroni et al., 2006). The stereo specific nature of [2,3]-sigmatropic rearrangement allows a complete transfer of chirality (Sweeney, 2009; Zhang & Wang, 2010). As first step in the conversion in deoxynojirimicine analogs (Asano et al., 2000; Watson et al., 2001), the reduction of the carbonyl with L-selectride gave, after chromatography and recrystallization, the title compound 4 as a single diastereoisomer. The structure determination confirms the configuration of the quaternary stereocentre formed during the domino sequence and the configuration of the carbinol function, which is in accordance with the attack of L-selectride at the opposite face of the ester function.

The structural model (Fig. 2) showed standard bond lengths and angles; the X-ray analysis confirmed a cis C7═C8 double bond in the azocine ring, and the stereochemistry of C atoms known from literature in the auxiliary chiral (–)-menthyl: S-C13, R-C12 and R-C16. Two new chiral centers were identified S-C1 and R-C10.

The crystal structure (Fig. 3 and 4) consists of one type of O—H···O hydrogen-bond, with each molecule acting as a donor and acceptor of two hydrogen bonds. One molecule is linked through hydrogen interaction to other two symmetry-related molecules in the crystal, resulting in the formation of chains parallel to the [010] direction.

All ¹H NMR (400 MHz) and ¹³C NMR (100 MHz) spectra were recorded on a Varian Mercury plus 400 spectrometer. Infrared (IR) spectra were performed on a FT/IR-480plus JASKO spectrophotometer. The optical rotations were measured by a polarimeter P-1010 JASCO in a 1 dm tube. All reagents and solvents employed were reagent grade materials purified by standard methods and redistilled before use. (1R)-(–)-menthyl acetate (>98%) and L-proline (>99.0%) were purchased from Sigma-Aldrich.

To a solution of compound 3 (210 mg, 0.6 mmol, see Fig. 1) in dry THF (5 ml) was added L-selectride (1.21 ml of 1.0 M solution in THF, 1.21 mmol) dropwise at 273 K. The reaction mixture was stirred for 1 h at 273 K and then allowed to warm to room temperature for another 1 h. The mixture was then diluted with EtOAc (50 ml) and filtered through a pad of silica gel, which was rinsed with EtOAc (50 ml). The filtrate was concentrated under reduced pressure, and the residue purified by flash chromatography (petroleum ether/ethyl acetate, 9:1) to give 180 mg of 4 (85%) as white oil. Recrystallization from EtOH/H₂O (8:2) gave the title compound 4 as white crystals: m.p. 389 K; [α]²⁵_D = -92.94 (c 0.32, CHCl₃); ¹H NMR (CDCl₃): δ 0.74 (d, 3H, J=7.0 Hz), 0.89 (d, 3H, J=6.8 Hz), 0.91 (d, 3H, J=6.8 Hz), 0.80–1.11 (m, 3H), 1.30–1.58 (m, 3H), 1.60–1.73 (m, 3H), 1.73–1.86 (m, 1H), 1.92–2.10 (m, 3H), 2.12–2.32 (m, 3H), 2.37 (d, 1H, J=8.4 Hz), 2.64–2.80 (m, 2H), 2.92 (ddd, 1H, J=15.8, 12.1, 3.1 Hz), 3.00 (dt, 1H, J=9, 5.2 Hz), 3.15 (dt, 1H, J=8.4, 5.2 Hz), 3.98 (q, 1H, J=8.0 Hz), 4.74 (dt, 1H, J=4.4, 10.8 Hz), 5.65–5.80 p.p.m. (m, 2H). ¹³C NMR (CDCl₃): δ 15.71, 20.90, 22.03, 22.91, 25.40, 25.89, 29.12, 31.39, 31.45, 32.50, 34.22, 41.18, 47.07 48.21, 50.04, 74.97, 75.08, 78.01, 126.17, 132.84, 173.64 p.p.m.; IR (neat): 3465, 3019, 2954, 1708, 1456, 1214 cm^-1. Anal. Calc. for C₂₁H₃₅NO₃: C 72.17, H 10.09, N 4.01%; Found: C 72.20, H 10.05, N 4.05%.

All C-bonded H atoms were fixed geometrically and treated as riding with C—H = 0.96 Å and with U_iso(H) = 1.2U_eq(carrier C). The hydroxyl H-atom H1o was located in a difference map, and included in the subsequent refinement with U_iso(H1o) = 1.2U_eq(O1). All H atoms were refined isotropically. The absolute configuration was assigned from the use of the chiral auxiliary (–)-menthyl (Wang et al., 2006) as the starting material, whose stereo centres are not involved in the reaction. Owing to the absence of significant anomalous dispersion for data collected with the Mo radiation, 2332 measured Friedel pairs were merged.

Symmetry code: (i) −x+1, y+1/2, −z+3/2.