6402
S.G. Davies et al. / Tetrahedron 67 (2011) 6382e6403
4.7.45. (S)-N-tert-Butoxy-N-10-(100-naphthyl)ethyl (S)-3-(N-isopropyl-
N-benzylamino)-3-phenylpropanamide 63.
(g) Bentley, S. A.; Davies, S. G.; Lee, J. A.; Roberts, P. M.; Russell, A. J.; Thomson, J.
E.; Toms, S. M. Tetrahedron 2010, 66, 4604; (h) Abraham, E.; Bailey, C. W.;
Claridge, T. D. W.; Davies, S. G.; Ling, K. B.; Odell, B.; Rees, T. L.; Roberts, P. M.;
Russell, A. J.; Smith, A. D.; Smith, L. J.; Storr, H. R.; Sweet, M. J.; Thompson, A. L.;
Thomson, J. E.; Tranter, G. E.; Watkin, D. J. Tetrahedron: Asymmetry 2010, 21,
1797.
Ph
N
O
2. For selected examples from this laboratory, see: (a) Bunnage, M. E.; Burke, A.
J.; Davies, S. G.; Goodwin, C. J. Tetrahedron: Asymmetry 1994, 5, 203; (b)
Davies, S. G.; Kelly, R. J.; Price Mortimer, A. J. Chem. Commun. 2003, 2132; (c)
Davies, S. G.; Burke, A. J.; Garner, A. C.; McCarthy, T. D.; Roberts, P. M.; Smith,
A. D.; Rodriguez-Solla, H.; Vickers, R. J. Org. Biomol. Chem. 2004, 2, 1387; (d)
Davies, S. G.; Haggitt, J. R.; Ichihara, O.; Kelly, R. J.; Leech, M. A.; Price Mor-
timer, A. J.; Roberts, P. M.; Smith, A. D. Org. Biomol. Chem. 2004, 2, 2630; (e)
Abraham, E.; Candela-Lena, J. I.; Davies, S. G.; Georgiou, M.; Nicholson, R. L.;
Ph
N
OtBu
Step 1: Following general procedure 6, tert-butyl (S)-3-amino-3-
phenylpropanoate (1.00 g, 4.50 mmol), acetone (0.66 mL,
9.00 mmol) and NaBH3CN (1.13 g, 18.0 mmol) were reacted in
MeOH (30 mL). Purification via flash column chromatography
(gradient elution, 1%/30% Et2O in 30e40 ꢁC petrol) gave tert-butyl
(S)-3-(N-isopropylamino)-3-phenylpropanoate as a colourless oil
ꢁ
ꢁ
Roberts, P. M.; Russell, A. J.; Sanchez-Fernandez, E. M.; Smith, A. D.; Thomson,
J. E. Tetrahedron: Asymmetry 2007, 18, 2510; (f) Abraham, E.; Davies, S. G.;
Millican, N. L.; Nicholson, R. L.; Roberts, P. M.; Smith, A. D. Org. Biomol. Chem.
2008, 6, 1655;
(g) Abraham, E.; Brock, E. A.; Candela-Lena, J. I.; Davies, S. G.; Georgiou, M.;
ꢁ
Nicholson, R. L.; Perkins, J. H.; Roberts, P. M.; Russell, A. J.; Sanchez-
(1.12 g, 94%); ½a D25
ꢀ23.1 (c 1.0 in CHCl3); nmax (film) 3328 (NeH),
ꢄ
ꢁ
Fernandez, E. M.; Scott, P. M.; Smith, A. D.; Thomson, J. E. Org. Biomol. Chem.
2008, 6, 1665; (h) Davies, S. G.; Fletcher, A. M.; Roberts, P. M.; Smith, A. D.
Tetrahedron 2009, 65, 10192; (i) Davies, S. G.; Hughes, D. G.; Price, P. D.;
Roberts, P. M.; Russell, A. J.; Smith, A. D.; Thomson, J. E.; Williams, O. M. H.
Synlett 2010, 567; (j) Davies, S. G.; Ichihara, O.; Roberts, P. M.; Thomson, J. E.
Tetrahedron 2011, 67, 216.
3. For selected examples from this laboratory, see: (a) Cailleau, T.; Cooke, J. W. B.;
Davies, S. G.; Ling, K. B.; Naylor, A.; Nicholson, R. L.; Price, P. D.; Roberts, P. M.;
Russell, A. J.; Smith, A. D.; Thomson, J. E. Org. Biomol. Chem. 2007, 5, 3922; (b)
Davies, S. G.; Durbin, M. J.; Goddard, E. C.; Kelly, P. M.; Kurosawa, W.; Lee, J. A.;
Nicholson, R. L.; Price, P. D.; Roberts, P. M.; Russell, A. J.; Scott, P. M.; Smith, A. D.
Org. Biomol. Chem. 2009, 7, 761.
4. For selected examples from this laboratory, see: (a) Davies, S. G.; Garner, A. C.;
Long, M. J. C.; Morrison, R. M.; Roberts, P. M.; Smith, A. D.; Sweet, M. J.; Withey,
J. M. Org. Biomol. Chem. 2005, 3, 2762; (b) Abraham, E.; Davies, S. G.; Docherty,
A. J.; Ling, K. B.; Roberts, P. M.; Russell, A. J.; Thomson, J. E.; Toms, S. M.
Tetrahedron: Asymmetry 2008, 19, 1356; (c) Davies, S. G.; Durbin, M. J.; Hartman,
S. J. S.; Matsuno, A.; Roberts, P. M.; Russell, A. J.; Smith, A. D.; Thomson, J. E.;
Toms, S. M. Tetrahedron: Asymmetry 2008, 19, 2870; (d) Aye, Y.; Davies, S. G.;
Garner, A. C.; Roberts, P. M.; Smith, A. D.; Thomson, J. E. Org. Biomol. Chem.
2008, 6, 2195.
5. Davies, S. G.; Smith, A. D.; Price, P. D. Tetrahedron: Asymmetry 2005, 16, 2833.
6. (a) Davies, S. G.; Hermann, G. J.; Sweet, M. J.; Smith, A. D. Chem. Commun. 2004,
1128; (b) Davies, S. G.; Fletcher, A. M.; Hermann, G. J.; Poce, G.; Roberts, P. M.;
Smith, A. D.; Sweet, M. J.; Thomson, J. E. Tetrahedron: Asymmetry 2010, 21, 1635.
7. Corey, E. J.; Ensley, H. E. J. Am. Chem. Soc. 1975, 97, 6908.
2968, 2932 (CeH), 1727 (C]O); dH (400 MHz, CDCl3) 0.98 (3H, d, J
6.3, NCHMeA), 1.04 (3H, d, J 6.3, NCHMeB), 1.38 (9H, s, CMe3), 1.86
(1H, br s, NH), 2.51 (1H, dd, J 15.2, 6.1, C(2)HA), 2.61 (1H, dd, J 15.2,
8.3, C(2)HB), 2.56e2.65 (1H, m, NCHMe2), 4.15 (1H, dd, J 8.3, 6.1, C(3)
H), 7.20e7.38 (5H, m, Ph); dC (100 MHz, CDCl3) 21.9, 24.2 (NCHMe2),
28.0 (CMe3), 44.7 (C(2)), 45.6 (NCHMe2), 57.0 (C(3)), 80.6 (CMe3),
127.1, 127.2, 128.4 (o,m,p-Ph), 143.1 (i-Ph), 171.0 (C(1)); m/z (ESIþ)
þ
264 ([MþH]þ, 100%); HRMS (ESIþ) C16H26NO2 ([MþH]þ) requires
264.1958; found 264.1956.
Step 2: Following general procedure 5, tert-butyl (S)-3-(N-
isopropylamino)-3-phenylpropanoate (1.12 g, 4.18 mmol) was
reacted with K2CO3 (5.25 g, 41.8 mmol) in BnBr (4.50 mL,
41.8 mmol). Purification via flash column chromatography (gradient
elution, 1%/20% Et2O in 30e40 ꢁC petrol) gave tert-butyl (S)-3-(N-
isopropyl-N-benzylamino)-3-phenylpropanoate as a colourless oil
(1.22 g, 83%); ½a D25
ꢀ17.0 (c 0.5 in CHCl3); nmax (film) 2972, 2932
ꢄ
(CeH), 1728 (C]O); dH (400 MHz, CDCl3) 0.86 (3H, d, J 6.6, NCHMeA),
1.07 (3H, d, J 6.6, NCHMeB), 1.28 (9H, s, CMe3), 2.56 (1H, dd, J 14.2, 9.5,
C(2)HA), 2.81 (1H, dd, J 14.2, 5.9, C(2)HB), 3.02e3.11 (1H, m, NCHMe2),
3.71 (2H, AB system, JAB 15.1, NCH2Ph), 4.29 (1H, dd, J 9.5, 5.9, C(3)H),
7.21e7.43 (10H, m, Ph); dC (100 MHz, CDCl3) 18.5, 21.1 (NCHMe2), 27.9
(CMe3), 40.1 (C(2)), 48.2 (NCHMe2), 49.4 (NCH2Ph), 60.5 (C(3)), 80.1
(CMe3), 126.4, 126.9, 128.0, 128.1, 128.3, 128.8 (o,m,p-Ph), 141.8, 142.2
(i-Ph), 171.3 (C(1)); m/z (ESIþ) 354 ([MþH]þ, 100%); HRMS (ESIþ)
8. (a) Chernega, A. N.; Davies, S. G.; Goodwin, C. J.; Hepworth, D.; Kurosawa, W.;
Roberts, P. M.; Thomson, J. E. Org. Lett. 2009, 11, 3254; (b) Davies, S. G.;
Goodwin, C. J.; Hepworth, D.; Roberts, P. M.; Thomson, J. E. J. Org. Chem. 2010,
75, 1214; (c) Chernega, A. N.; Davies, S. G.; Fletcher, A. M.; Goodwin, C. J.;
Hepworth, D.; Prasad, R. S.; Roberts, P. M.; Savory, E. D.; Smith, A. D.; Thomson,
J. E. Tetrahedron 2010, 66, 4167.
9. For a review, see: Whitesell, J. Chem. Rev. 1992, 92, 953.
C23H32NO2 ([MþH]þ) requires 354.2428; found 354.2427.
þ
10. For instance, see: (a) Kaneko, T.; Turner, D. L.; Newcomb, M.; Bergbreiter, D. E.
Tetrahedron Lett. 1979, 20, 103; (b) Whitesell, J. K.; Bhattacharya, A.; Henke, K. J.
Chem. Soc., Chem. Commun. 1982, 988; (c) Yamamoto, Y.; Maeda, M.; Maruyama,
K. J. Chem. Soc., Chem. Commun. 1983, 774; (d) Comins, D. L.; Goehring, R. R.;
Joseph, S. P.; O’Connor, S. J. Org. Chem. 1990, 55, 2574.
Step 3: Following general procedure 2, a solution of tert-butyl
(S)-3-(N-isopropyl-N-benzylamino)-3-phenylpropanoate (1.13 g,
4.14 mmol) in CH2Cl2 (12.0 mL) was treated with TFA (12.0 mL) to
give a white foam (1.00 g). Then, following general procedure 3,
a solution of the residue (312 mg) in CH2Cl2 (4 mL) was reacted
with (COCl)2 (0.18 mL, 2.10 mmol) and a mixture of (S)-8$(þ)-CSA8a
(200 mg, 0.42 mmol) and K2CO3 (580 mg, 4.20 mmol) in CH2Cl2
(2 mL). Purification via flash column chromatography (gradient
elution, 1%/10% Et2O in 30e40 ꢁC petrol) gave 63 as a colourless
oil (19 mg, 8%, >95:5 dr).
11. For instance, see: (a) Boeckman, R. K., Jr.; Naegely, P. C.; Arthur, S. D. J. Org. Chem.
1980, 45, 752; (b) Swindell, C. S.; Tao, M. J. Org. Chem. 1993, 58, 5889; (c) Rigby,
J. H.; Sugathapaia, P.; Heeg, M. J. J. Am. Chem. Soc. 1995, 117, 8851; (d) Serells, A.
K.; Simpson, G. W. Tetrahedron Lett. 1997, 38, 4277; (e) Oppolzer, W.; Kurth, M.;
Reichlin, D.; Chapuis, C.; Mohnhaupt, M.; Moffatt, F. Helv. Chim. Acta 1981, 64,
2802.
€
12. For instance, see: (a) Oppolzer, W.; Robbiani, C.; Battig, K. Helv. Chim. Acta 1980,
63, 2015; (b) Whitesell, J. K.; Bhattacharya, A.; Aguilar, D. A.; Henke, K. J. Chem.
Soc., Chem. Commun. 1982, 989.
13. Muniz, K.; Iesato, A.; Nieger, M. Chem.dEur. J. 2003, 9, 5581.
14. For instance, see: (a) Donohoe, T. J.; Guyo, P. M.; Helliwell, M. Tetrahedron Lett.
Acknowledgements
€
€
1999, 40, 435; (b) Sebek, M.; Holz, J.; Borner, A.; Jahnisch, K. Synlett 2009, 461.
15. For instance, see: (a) Anderson, J. C.; O’Loughlina, J. M. A.; Tornosb, J. A. Org.
Biomol. Chem. 2005, 3, 2741; (b) Tayama, E.; Kimura, H. Angew. Chem., Int. Ed.
2007, 46, 8869; (c) Tayama, E.; Orihara, K.; Kimura, H. Org. Biomol. Chem. 2008,
6, 3673.
The authors would like to thank the EPSRC and SCI-Ink for
a Dorothy Hodgkin Postgraduate Award (J.Y.).
16. For instance, see: (a) Koch, H.; Runsink, J.; Scharf, H.-D. Tetrahedron Lett. 1983,
24, 3217; (b) Little, R. D.; Moeller, K. D. J. Org. Chem. 1983, 48, 4487.
17. For instance, see: (a) Kozikowski, A. P.; Tuckmantel, W.; Liao, Y.; Manev, H.;
References and notes
€
Ikonomovic, S.; Wroblewskil, J. T. J. Med. Chem. 1993, 36, 2706; (b) Kozikowski,
A. P.; Zhao, L.; Zhang, A.; Wang, C. Z.; Flippen-Anderson, J.; Johnson, K. M.
ChemMedChem 2006, 1, 58.
1. (a) Davies, S. G.; Ichihara, O. Tetrahedron: Asymmetry 1991, 2, 183; (b) Costello, J.
F.; Davies, S. G.; Ichihara, O. Tetrahedron: Asymmetry 1994, 5, 1999; (c) Davies, S.
G.; Garrido, N. M.; Kruchinin, D.; Ichihara, O.; Kotchie, L. J.; Price, P. D.; Price
Mortimer, A. J.; Russell, A. J.; Smith, A. D. Tetrahedron: Asymmetry 2006, 17, 1793;
(d) Davies, S. G.; Nicholson, R. L.; Price, P. D.; Roberts, P. M.; Russell, A. J.; Savory,
E. D.; Smith, A. D.; Thomson, J. E. Tetrahedron: Asymmetry 2009, 20, 758; (e)
Davies, S. G.; Garner, A. C.; Nicholson, R. L.; Osborne, J.; Roberts, P. M.; Savory, E.
D.; Smith, A. D.; Thomson, J. E. Org. Biomol. Chem. 2009, 7, 2604; (f) Davies, S. G.;
Mujtaba, N.; Roberts, P. M.; Smith, A. D.; Thomson, J. E. Org. Lett. 2009, 11, 1959;
€
18. For instance, see: (a) Oppolzer, W.; Loher, H. J. Helv. Chim. Acta 1981, 64, 2808;
ꢁ
(b) Barluenga, J.; Montserrat, J. M.; Florez, J.; García-Granda, S.; Martín, E.
Angew. Chem. 1994, 106, 1451; (c) Murthy, K. S. K.; Rey, A. W.; Tjepkema, M.
Tetrahedron Lett. 2003, 44, 5355; (d) Lee, C. K. Y.; Herlt, A. J.; Simpson, G. W.;
Willis, A. C.; Easton, C. J. J. Org. Chem. 2006, 71, 3221; (e) Ikeda, S.; Shibuya, M.;
Kanoh, N.; Iwabuchi, Y. Org. Lett. 2009, 11, 1833.