a yellow oil. This residue was purified by FCC (petrol–Et2O 2 : 1)
to yield diene 31 (41 mg, 78%) as a yellow oil; [a]2D0 −57.1 (c = 0.8,
CHCl3); mmax/cm −1 (film) 2922 (w), 1677 (s), 1603 (w), 1408 (m),
1028 (m); dH (270 MHz, CDCl3) 2.52 (1H, dd, J = 13.5 and10.0Hz,
C5–CH2Ph), 3.21 (1H, dd, J = 13.5 and 5.5 Hz, C5–CH2Ph), 4.01–
4.10 (1H, m, C5–H), 4.20 (1H, d, J = 15.0 Hz, NCH2Ph), 5.22
(1H, d, J = 15.0 Hz, NCH2Ph), 6.20 (1H, dd, J = 11.0 and 1.5 Hz,
experiments. Observed NOE correlations: C3–H → C4–H, C4–
Bu; C4–H → C5–CH2Ph, C5–H, C3–H, C3–Ph, C4–Bu; C5–H →
C4–H, C4–Bu, C5–CH2Ph; C5–CH2Ph → C4–H, C5–H, C3–Ph.
◦
Data for cis product 35: mp 96.5–98 C (Et2O–hexanes); [a]D20
+17.1 (c = 0.7, CHCl3); mmax/cm−1 (film) 2929 (m), 1686 (s), 1496
(m), 1455 (m), 1249 (m), 1079 (m); dH (400 MHz, CDCl3) 0.52
(3H, t, J = 7.0 Hz, (CH2)3CH3), 0.56–0.97 (6H, m, (CH2)3CH3),
2.17–2.26 (1H, m, C4–H), 2.82 (1H, dd, J = 13.5 and 8.0 Hz, C5–
CH2Ph), 3.06 (1H, dd, J = 13.5 and 4.5 Hz, C5–CH2Ph), 3.34–3.41
(1H, m, C5–H), 3.84 (1H, d, J = 8.5 Hz, C3–H), 4.56 (1H, d, J =
14.5 Hz, NCH2Ph), 5.30 (1H, d, J = 14.5 Hz, NCH2Ph), 7.08–
7.18 (4H, m, ArCH), 7.20–7.43 (11H, m, ArCH); dC (100 MHz,
CDCl3) 13.6 ((CH2)3CH3), 22.1, 28.6 and 29.0 ((CH2)3CH3), 38.4
(C5–CH2Ph), 42.0 (C-4), 44.8 (NCH2Ph), 50.8 (C-3), 61.1 (C-
5), 126.8, 126.9, 127.8, 128.3, 128.6, 128.7 (2 signals), 129.4 and
129.9 (ArCH × 15), 136.2, 136.7 and 137.5 (ArC × 3), 174.3
(C-2); HRMS (ESI+): found: [M + H]+ 398.2490, C28H32NO
requires 398.2478. The enantiomeric purity of this compound was
determined by chiral HPLC (Chira◦ lpak AD-H, isocratic hexanes–
i-PrOH 96 : 4, 1.0 mL min−1, 20 C); tR (major) = 43.8 min and
tR (minor) = 41.7 min. The relative stereochemical assignment
of this product was assigned on the basis of field gradient NOE
experiments. Observed NOE correlations: C3–H → C4–H, C5–
CH2Ph; C4–H → C5–CH2Ph, C5–H, C3–H, C3–Ph, C4–Bu; C5–
H → C4–H, C4–Bu, C3–Ph, C5–CH2Ph; C5–CH2Ph → C3–H,
C4–H, C5–H; C3–Ph → C4–Bu.
=
=
CH CH2), 6.30 (1H, dd, J = 17.5 and 1.5 Hz, CH CH2), 6.44
(1H, dd, J = 17.5 and 11.0 Hz, CH=CH2), 6.68 (1H, s, C4–H),
7.05–7.15(2H, m, ArCH), 7.20–7.43(8H, m, ArCH); dc (100 MHz,
CDCl3) 38.0 (C5–CH2Ph), 44.1 (NCH2Ph), 60.5 (C-5), 119.8 (C-
8), 127.0, 127.3, 127.6, 128.1, 128.7, 128.8 and 129.2 (ArCH ×
10 and C-3), 134.5, 136.4 and 137.5 (ArC × 2 and C-4), 140.7
(C-7), 170.0 (C-2); HRMS (ESI+): found [M + Na]+ 312.1359,
C20H19NONa requires 312.1359. The enantiomeric purity of this
compound was determined by chiral HPLC (◦Chiralcel OJ-H,
isocratic hexanes–i-PrOH 95 : 5, 1.0 mL min−1, 20 C); tR (major) =
41.3 min and tR (minor) = 25.1 min.
(3S,4R,5S)-1,5-Dibenzyl-4-butyl-3-phenylpyrrolidin-2-one (34)
and (3R,4R,5S)-1,5-dibenzyl-4-butyl-3-phenylpyrrolidin-2-one
(35). To a suspension of CuI (112 mg, 0.59 mmol) in anhydrous
THF (0.5 mL) at 0 ◦C was added, via syringe, n-BuLi in hexanes
(1.6 M, 1.12 mmol) to form a brown suspension. After 10 min the
◦
mixture was cooled to −78 C and TMSCl (35 lL, 0.282 mmol)
and hexamethylphosphoramide (HMPA, 65 lL, 0.37 mmol) were
sequentially added via syringe. After a further 5 minutes a solution
of arylated lactam 30 (53 mg, 0.16 mmol) in anhydrous THF
(0.75 mL) was added, via syringe, and the mixture was stirred at rt
for 5 h. Saturated aq. NH4Cl (10 mL) was added and the mixture
was diluted with Et2O (15 mL). The organic portion was isolated
and washed with saturated aq. NH4Cl (10 mL) and water (2 ×
10 mL), dried (Na2SO4) and concentrated in vacuo to afford a
yellow oil. This residue was purified by FCC (hexanes–Et2O 2 : 1)
to yield trans-lactam 34 (28 mg, 50%, >98% ee) and subsequently
cis-lactam 35 (9 mg, 15%, >98% ee) as colourless solids.
Acknowledgements
We thank GSK and EPSRC for studentships (to AJW and JFB).
References
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tR (minor) = 24.1 min. The relative stereochemical assignment
of this product was assigned on the basis of field gradient NOE
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