1.
Tschantz, M. A.; Burgess, L. E.; Meyers, A. I. Org. Synth., Coll. Vol. IX 1998, 530.
2.
(S)-(+)-2-Phenylglycinol is commercially available, or may be prepared by reducing (S)-(+)-2-phenylglycine as follows: A 1-L, three-necked, round-bottomed flask is charged with 200 mL of dry THF under an argon atmosphere. Portionwise, 10.01 g of sodium borohydride (264.6 mmol) is added, followed by the dropwise addition of 65.1 mL of boron trifluoride etherate (528.7 mmol). The colorless suspension is stirred for 15 min, followed by portionwise addition of 20.00 g of (S)-(+)-2-phenylglycine (132.2 mmol). (CAUTION: exotherm and gas evolution!). The resulting suspension is heated at reflux for 12 hr and then is allowed to cool to room temperature followed by quenching with methanol until gas evolution ceases. The reaction mixture is concentrated under reduced pressure to yield a colorless solid that is taken up in 400 mL of 20% aqueous sodium hydroxide solution. The basic solution is extracted three times with 200-mL portions of dichloromethane, the combined organic layers are dried over sodium sulfate, and concentrated under reduced pressure to yield 14.72 g (81%) of (S)-(+)-2-phenylglycinol as a colorless solid: mp 72–74°C, [α]D +32.2°; 1H NMR (300 MHz, CDCl3) δ: 3.52 (dd, 1 H, J = 10.7, 8.3), 3.71 (dd, 1 H, J = 10.7, 4.4), 4.01 (dd, 1 H, J = 8.2, 4.4), 7.23–7.35 (m, 5 H).
3.
Merck 951 grade silica gel was used. Chromatography was performed in the manner described by Still2 using ~ 20:1 (w/w) of silica gel to crude product.
4.
The spectral data of the purified bicyclic lactam are as follows: 1H NMR (300 MHz, CDCl3) δ: 0.85 (t, 3 H, J = 6.4), 1.13–1.72 (m, 12 H), 2.13 (m, 1 H), 2.33 (ddd, 1 H, J = 13.4, 9.7, 2.5), 2.57 (ddd, 1 H, J = 17.3, 10.2, 2.5), 2.81 (m, 1 H), 4.05 (dd, 1 H, J = 8.7, 7.3), 4.62 (t, 1 H, J = 8.5), 5.17 (t, 1 H, J = 7.7), 7.20–7.36 (m, 5 H); 13C NMR (75.5 MHz, CDCl3) δ: 14.0, 22.5, 23.9, 29.1, 29.5, 30.9, 31.6, 33.3, 36.3, 57.5, 72.8, 102.7, 125.4, 127.3, 128.6, 140.1, 179.3; IR (thin film) cm−1: 2954–2856, 2362, 1715, 1458, 1364, 1031, 699.
5.
Dichloromethane was freshly distilled over calcium hydride.
6.
Triethylsilane was purchased from Aldrich Chemical Company, Inc. and used without further purification.
7.
Titanium tetrachloride was purchased from Fluka Chemical Corporation and used without further purification.
8.
The checkers used an internal thermometer and maintained the reaction temperature between −78° and −70°C during the addition.
9.
The spectral data of the purified hydroxyalkyl lactam are as follows: 1H NMR (300 MHz, CDCl3, 5 mg/mL) δ: 0.86 (t, 3 H, J = 6.6), 1.05–1.40 (m, 11 H), 1.58 (m, 1 H), 1.75 (m, 1 H), 2.07 (m, 1 H), 2.40–2.59 (m, 2 H), 2.95 (s (br), 1 H), 3.33 (m, 1 H), 3.95 (dd, 1 H, J = 12.3, 3.3), 4.22 (dd, 1 H, J = 12.3, 7.8), 4.41 (dd, 1 H, J = 7.8, 3.3), 7.20–7.37 (m, 5 H); 13C NMR (75.5 MHz, CDCl3) δ: 14.0, 22.6, 24.1, 24.5, 29.1, 29.4, 31.3, 31.7, 32.3, 59.3, 62.3, 64.1, 127.2, 127.8, 128.7, 137.5, 176.8; IR (thin film) cm−1: 3377 (br), 2959–2856, 1668, 1451, 1420, 1285, 1064, 702. The 1H NMR signal for the proton of the OH group (δ 2.95) was found to be concentration dependent.
10.
Lithium wire was purchased from Aldrich Chemical Company, Inc., and was cut into small pieces.
11.
The solution should remain blue for the duration (30 min). More lithium may be added if necessary.
12.
The final product is difficult to visualize during TLC analysis. Ninhydrin (5% w/v in ethanol) or ceric ammonium nitrate (5 g in 100 mL of aqueous 1 M H2SO4) are effective.
13.
The spectral data for the purified pyrrolidinone are as follows: 1H NMR (300 MHz, CDCl3, 5 mg/mL) δ: 0.86 (t, 3 H, J = 6.4), 1.25–1.75 (m, 13 H), 2.20–2.35 (m, 3 H), 3.61 (quintet, 1 H, J = 6.9), 6.09 (s (br), 1 H); 13C NMR (75.5 MHz, CDCl3) δ: 14.0, 22.6, 25.8, 27.3, 29.1, 29.4, 30.2, 31.7, 36.7, 54.7, 178.2; IR (thin film) cm−1: 3204 (br), 2956–2856, 1700, 1463, 1387, 1311, 1266. [α]D −9.7° (CHCl3, c 1.1).