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DOI: 10.1055/s-2004-822926
General and Facile Synthesis of 1,2-Amino Alcohols
Publication History
Publication Date:
10 May 2004 (online)
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Abstract
Facile preparation of 1,2-amino alcohols has been achieved by the reaction of benzyloxymethyl lithium with imines, which are generated from α-amido sulfones and benzyloxymethyl lithium in situ at -78 °C in THF.
Key words
amino alcohol - α-amidoalkyl phenylsulfone - benzyloxymethyl lithium - nucleophilic addition - activated imine
- 1
Bergmeier SC. Tetrahedron 2000, 56: 2561 -
2a
Reetz M. Angew. Chem., Int. Ed. Engl. 1991, 30: 1531 -
2b
Ohfune Y. Acc. Chem. Res. 1992, 25: 360 -
2c
Yokomatsu T.Yuasa Y.Shibuya S. Heterocycles 1992, 33: 1051 -
2d
Golebiowski A.Jurczak J. Synlett 1993, 241 -
2e
Gante J. Angew. Chem., Int. Ed. Engl. 1994, 33: 1699 -
3a
Umezawa H.Aoyagi T.Morishima H.Matsuzaki M.Hamada M.Takeuchi T. J. Antibiot. 1970, 23: 259 -
3b
Aoyagi T.Tobe H.Kojima F.Hamada M.Takeuchi T.Umezawa H. J. Antibiot. 1978, 31: 636 -
3c
Umezawa H.Aoyagi T.Suda H.Hamada M.Takeuchi T. J. Antibiot. 1976, 29: 97 -
3d
Arcamone F.Cassinelli G.Orezzi P.Franceschi G.Mondelli R. J. Am. Chem. Soc. 1964, 86: 5334 -
3e
Iwamoto RH.Lim P.Bhacca NS. Tetrahedron Lett. 1968, 36: 3891 -
4a
Kim YH. Acc. Chem. Res. 2001, 34: 955 -
4b
Anand NK.Carreira EM. J. Am. Chem. Soc. 2001, 123: 9687 -
4c
Corey EJ.Helal CJ. Angew. Chem. Int. Ed. 1998, 37: 1986 - 5
Chen YK.Lurain AE.Walsh PJ. J. Am. Chem. Soc. 2002, 124: 12225 ; and references therein -
6a
Ager DJ.Prakash I.Schaad DR. Chem. Rev. 1996, 96: 835 -
6b
Larrow JF.Schaus SE.Jacobsen EN. J. Am. Chem. Soc. 1996, 118: 7420 -
6c
Barret AGM.Seefeld MA.White AJP.Williams DJ. J. Org. Chem. 1996, 61: 2677 -
6d
Shibasaki M.Sasai H. Pure. Appl. Chem. 1996, 68: 523 -
6e
DuBois J.Tomooka CS.Hong J.Carreira EM. J. Am. Chem. Soc. 1997, 119: 3179 -
6f
Bruncko M.Schilingloff G.Sharpless KB. Angew. Chem., Int. Ed. Engl. 1997, 36: 1483 -
6g
Kobayashi S.Ishitani H.Ueno M. J. Am. Chem. Soc. 1998, 120: 431 -
6h
Tomoyasu T.Tomooka K.Nakai T. Synlett 1998, 1147 -
6i
Chung SK.Lee JM. Tetrahedron: Asymmetry 1999, 10: 1441 -
7a
Nugent WA. J. Am. Chem. Soc. 1992, 114: 2768 -
7b
Enders D.Jegelka U.Ducker B. Angew. Chem., Int. Ed. Engl. 1993, 32: 423 -
7c
Barrett AGM.Seefeld MA. Tetrahedron 1993, 49: 7857 -
7d
Matsubara S.Ukita H.Kodama T.Utimoto K. Chem. Lett. 1994, 831 -
7e
Lingibe O.Graffe B.Sacquet MC.Lhommet G. Heterocycles 1994, 37: 1469 -
7f
Besse P.Veschambre H.Chenevert R.Dickman M. Tetrahedron: Asymmetry 1994, 5: 1727 - 8
Enders D.Reinhold U. Angew. Chem., Int. Ed. Engl. 1995, 34: 1219 - 9
Caron M.Carlier PR.Sharpless KB. J. Org. Chem. 1985, 53: 5185 - 10
Wuts PG.Pruitt LE. Synthesis 1989, 622 -
11a
Youn SW.Choi JY.Kim YH. Chirality 2000, 12: 404 -
11b
Tang TP.Volkman SK.Ellman JA. J. Org. Chem. 2001, 66: 8772 -
11c
Petasis NA.Zavialov IA. J. Am. Chem. Soc. 1998, 120: 11798 -
12a
Pearson WH.Lindbeck AC. J. Am. Chem. Soc. 1991, 113: 8546 -
12b
Mecozzi T.Petrini M. J. Org. Chem. 1999, 64: 8970 -
12c
Bernacka E.Klepacz A.Zwierzak A. Tetrahedron Lett. 2001, 42: 5093 - 13
Still WC. J. Am. Chem. Soc. 1978, 100: 1481
References
Representative Experimental Procedure for Addition of Benzyloxymethyl Lithium Reagent to α-Amidoalkyl Phenylsulfones (Table 2, Entry 6).
Benzyloxymethyltributylstannane (2.5 mmol), prepared according to ref.13, was dissolved in THF (5 mL) and charged with argon. This solution was cooled to -78 °C and n-BuLi (1.24 mL, 2.48 mmol, 2.0 M solution in cyclohexane) was added dropwise to this cooled solution. After stirring for 10 min, the solution became yellowish, and the solution of α-amidoalkyl phenylsulfone 1 g (1 mmol) in 2 mL of THF was added in one portion. The mixture was stirred for 1.5 h. The reaction mixture was quenched with sat. aq solution of NH4Cl, diluted and extracted with Et2O, dried over MgSO4 and evaporated to give crude 4g, which was purified by silica gel chromatography, (eluent: EtOAc-n-hexane, 1:10) to give pure 4g in 81% yield. 1H NMR (300 MHz, CDCl3): δ = 0.88 (d, 3 H), 0.91 (d, 3 H), 1.42 (s, 9 H), 1.87 (m, 1 H), 3.46 (m, 3 H), 4.46 (q, 2 H), 4.71 (d, 1 H), 7.28 (m, 5 H). 13C NMR (75 MHz, CDCl3): δ = 18.5, 19.5, 28.4, 29.7, 55.7, 70.6, 73.2, 78.9, 127.4, 127.6, 128.3, 138.3, 155.9. MS (EI): Anal. Calcd for C17H27NO3: 293.1991. Found: 292.21.
Experimental Procedure for Addition of Benzyloxymethyl Lithium Reagent to in situ-Generated Imine 3 (Table 1, Entry 8).
To a suspension of 40 mg of NaH in 2 mL of THF under argon, 1 mmol of 1a in 1 mL of THF was added and the resulting mixture was stirred for 30 min. The solution was added to the cold (-78 °C) benzyloxymethyl lithium solution containing 1.5 mmol of benzyloxymethyl lithium.14 After stirring for 30 min, the reaction mixture was quenched with sat. aq solution of NH4Cl, diluted and extracted with Et2O, dried over MgSO4 and evaporated to give crude 4a, which was purified by silica gel chromatography, (eluent: EtOAc-n-hexane, 1:10) to give 4a in 83% yield. 1H NMR (300 MHz, CDCl3): δ = 1.25 (s, 9 H), 3.61 (q, 2 H), 3.70 (q, 2 H), 4.48 (q, 2 H), 4.84 (br, 1 H), 5.25 (br, 1 H), 7.28 (m, 10 H). 13C NMR (75 MHz, CDCl3): δ = 28.3, 54.7, 70.3, 73.1, 79.5, 126.7, 127.2, 127.5, 127.6, 127.8, 137.9, 140.6, 155.3. MS (EI): Anal. Calcd for C20H25NO3: 327.1834. Found: 326.41.
Representative Procedure for Acidic Deprotection of Boc Group (compound 5). To 4a (50 mg) in MeOH (2 mL) was added 2 mL of 4 N HCl/1,4-dioxane. The solution was stirred for 3 h at 25 °C. After TLC analysis of the completion of the reaction, the solution was concentrated in vacuo. The resulting crude 5 was recrystallized from CHCl3-Et2O to give pure 5 in 92% yield. 1H NMR (300 MHz, CDCl3): δ = 3.73 (m, 2 H), 4.33 (br, 1 H), 4.50 (q, 2 H), 7.25 (m, 10 H), 8.96 (br, 3 H). 13C NMR (75 MHz, CDCl3): δ = 52.6, 74.9, 76.1, 125.7, 126.6, 127.1, 127.3, 128.1, 129.5, 137.2, 141.3.