water and brine. The residue obtained after drying (MgSO4) and removal of the solvent in vacuo was
subjected to flash chromatography (SiO2, 5 % EtOAc/petrol) to yield the product as a white solid (237 mg,
74 %), mp 51–52 °C; νmax (KBr disk)/cm–1 1661s, 1512w, 1407m, 1360m, 1328m, 773m, 718m; δH
(200 MHz, CDCl3) 5.52 (2H, s), 6.22 (1H, d, J 2.7 Hz), 6.88 (1H, d, J 2.7 Hz), 7.14–7.40 (5H, m),
+
9.78 (1H, s); m/z (C.I., NH3) 222 (M(37Cl)H+, 25), 220 (M(35Cl)H+, 100), 91 (C7H7 , 53 %); Accurate
mass: Found 220.0529; C12H11NOCl (MH+) requires 220.0529.
1-Benzyl-3-chloro-2-(1-hydroxyprop-2-en-1-yl)pyrrole (10)
To a solution of 1-benzyl-3-chloro-2-formylpyrrole (520 mg, 2.37 mmol) in THF (50 mL) at 0 °C was
added vinylmagnesium bromide (4.7 mL of a 1.0 M solution in THF, 4.7 mmol) and the mixture stirred for
30 min. The reaction was quenched with saturated NH4Cl solution then partitioned between ether and
water; the combined organic portions were washed with brine then dried (MgSO4) and concentrated to yield
the somewhat unstable crude product (10) as a yellow oil (593 mg, quant.) that was used directly in the
next reaction. νmax (film)/cm–1 3681w, 3613w, 3020s, 1746w, 1670m, 1522m, 1421m, 1221s, 1028m,
929m, 730vs; δH (500 MHz, CDCl3) 5.23 (2H, ABq, J 15.9 Hz), 5.20 (1H, apparent dt, J 10.4, 1.5 Hz),
5.30 (1H, apparent dt, J 17, 1.5 Hz), 5.5–5.58 (1H, m), 6.09 (1H, ddd, J 17, 10.4, 4.5 Hz), 6.16 (1H,
d, J 3 Hz), 6.56 (1H, d, J 3 Hz), 7.09–7.40 (5H, m).
1-Benzyl-3-chloro-2-[1-(2-methoxyprop-2-en-1-yl)oxyprop-2-en-1-yl]pyrrole (11)
To a suspension of NaH (287 mg of a 60 % dispersion in oil, 7.18 mmol) in THF (50 mL) at 0 °C was
added alcohol (10) (593 mg, 2.4 mmol) as a solution in THF (5 mL) and the mixture was stirred for 30
min. 2-Methoxyallyl bromide13 (1.15 g, ca. 63 % pure, ca. 4.8 mmol) and tetrabutylammonium iodide (44
mg, 0.12 mmol) were added sequentially and the mixture was allowed to warm up to rt over 13 h. The
reaction was quenched with water, the aqueous layer was extracted with ether, and the combined organic
extracts were washed with brine then dried (MgSO4) and concentrated to yield an oil. Purification by flash
chromatography (SiO2, 2:4:94 EtOAc:Et3N:petrol) afforded the product (11) as a colorless oil (601 mg, 80
% from 1-benzyl-3-chloro-2-formylpyrrole). νmax (film)/cm–1 2936m, 1666m, 1630m, 1496m, 1453s,
1300s, 1258m, 1110s, 1079s, 926m; δH (500 MHz, CDCl3) 3.55 (3H, s), 3.77 (2H, ABq, J 12.8 Hz),
4.05 (1H, d, J 2.2 Hz), 4.13 (1H, d, J 2.2 Hz), 4.91 (1H, d, J 6.7 Hz), 5.14 (2H, ABq, J 15.4 Hz), 5.13
(1H, apparent dt, J 10.6, 1.6 Hz), 5.20 (1H, apparent dt, J 17.3, 1.6 Hz), 5.99 (1H, ddd, J 17.3, 10.6,
6.7 Hz), 6.08 (1H, d, J 3 Hz), 6.46 (1H, d, J 3 Hz), 7.08 (2H, 2 x d, J 7.1 Hz), 7.25–7.32 (3H, m); δC
(125 MHz, CDCl3) 51.5, 54.9, 68.4, 72.6, 83.5, 107.8, 112.7, 116.1, 121.9, 125.3, 127.4, 127.5,
128.5, 136.4, 137.7, 159.8; m/z (C.I., NH3) 320 (M(37Cl)H+, 3), 318 (M(35Cl)H+, 8), 261 (10), 232
(54), 230 (100), 91 (35), 89 (54 %); Anal. Calcd for C18H20NO2Cl: C, 68.03; H, 6.34; N, 4.41. Found:
C, 68.58; H, 6.00; N, 4.40; Accurate mass: Found 318.1259; C18H21NOCl (MH+) requires 318.1261.
ACKNOWLEDGMENTS
We thank Jonathan Peverley for preliminary experiments, the EPSRC for a fellowship (NK and YZ), and
Pfizer Central Research and AstraZeneca for generous unrestricted support.