Abstract
Asymmetric aldol additions using chlorotitanium enolates of N -acyl oxazolidinones, oxazolidinethiones and thiazolidinethiones proceed with high diastereoselectivity for the ‘Evans syn ’ product using one equivalent of titanium tetrachloride, one equivalent of diisopropylethylamine and one equivalent of N -methyl-2-pyrrolidinone. Typical selectivities of 94:6 to >98:2 were obtained using N -propionyl oxazolidinones, oxazolidinethiones and thiazolidinethiones at 0 °C with stoichiometric amounts of aldehyde. Glycolate imides also gave high selectivities and high yields using this procedure.
Key words
aldol reactions - asymmetric synthesis - titanium enolates - imides - glycolates
References
1a
Walker MA.
Heathcock CH.
J. Org. Chem.
1991,
56:
5747
1b
Arya P.
Qin H.
Tetrahedron
2000,
56:
917
1c
Ager DJ.
Prakash I.
Schaad DR.
Aldrichimica Acta
1997,
30:
3
1d
Velazquez F.
Olivo HF.
Curr. Org. Chem.
2002,
6:
303
1e
Evans DA.
Shaw JT.
Actualité Chimique
2003,
35
For selected examples see:
2a
Evans DA.
Kaldor SW.
Jones TK.
Clardy J.
Stout TJ.
J. Am. Chem. Soc.
1990,
112:
7001
2b
Evans DA.
Gage JR.
Leighton JL.
J. Am. Chem. Soc.
1992,
114:
9434
2c
Evans DA.
Ng HP.
Rieger DL.
J. Am. Chem. Soc.
1993,
115:
11446
2d
Evans DA.
Fitch DM.
J. Org. Chem.
1997,
62:
454
2e
Evans DA.
Kim AS.
Metternich R.
Novack VJ.
J. Am. Chem. Soc.
1998,
120:
5921
2f
Crimmins MT.
King BW.
J. Am. Chem. Soc.
1998,
120:
9084
2g
Crimmins MT.
King BW.
J. Org. Chem.
1996,
61:
4192
2h
Crimmins MT.
Katz JD.
Washburn DG.
Allwein SP.
MacAtee LF.
J. Am. Chem. Soc.
2002,
124:
5661
3
Evans DA.
Bartroli J.
Shih TL.
J. Am. Chem. Soc.
1981,
103:
2127
4
Evans DA.
Rieger DL.
Bilodeau MT.
Urpi F.
J. Am. Chem. Soc.
1991,
113:
1047
5a
Nerz-Stormes M.
Thornton ER.
J. Org. Chem.
1991,
56:
2489
5b
Bonner MP.
Thornton ER.
J. Am. Chem. Soc.
1991,
113:
1299
6a
Yan T.-H.
Tan C.-W.
Lee H.-C.
Lo H.-C.
Huang T.-Y.
J. Am. Chem. Soc.
1993,
115:
2613 ; and references therein
6b
Yan T.-H.
Hung A.-W.
Lee H.-C.
Chang C.-S.
Liu W.-H.
J. Org. Chem.
1995,
60:
3301
7a
Nagao Y.
Hagiwara Y.
Kumagai T.
Ochiai M.
Inoue T.
Hashimoto K.
Fujita E.
J. Org. Chem.
1986,
51:
2391
7b
Hsiao C.-N.
Liu L.
Miller MJ.
J. Org. Chem.
1987,
52:
2201
8a
Crimmins MT.
King BW.
J. Am. Chem. Soc.
1998,
120:
9084
8b
Crimmins MT.
Chaudhary K.
Org. Lett.
2000,
2:
775
9
Crimmins MT.
King BW.
Tabet EA.
Chaudhary K.
J. Org. Chem.
2001,
66:
894
10a
Zhang W.
Carter RG.
Yokochi AFT.
J. Org. Chem.
2004,
69:
2569
10b
Crimmins MT.
McDougall PJ.
Org. Lett.
2003,
5:
591
10c
Ambhaikar NB.
Snyder JP.
Liotta DC.
J. Am. Chem. Soc.
2003,
125:
3690
10d
Guz NR.
Phillips AJ.
Org. Lett.
2002,
4:
2253
11
Typical Procedure for Formation of Evans
syn
Adducts from
N
-Propionylimides 1a, 1b, and 1c. To a dry round-bottom flask under argon was added 1.00 mmol of the appropriate N -acyloxazolidinone, N -acyloxazolidinethione, or N -propionylthiazolidinethione, and 10 mL CH2 Cl2 . After cooling to 0 °C, TiCl4 (0.115 mL, 1.05 mmol) was added dropwise and the solution was allowed to stir for 15 min. Diisopropylethylamine (0.191 mL, 1.10 mmol) was added dropwise to the mixture and the solution was allowed to stir for 40 min. 1-Methyl-2-pyrrolidinone (0.096 mL, 1.00 mmol for N -acyloxazolidinone and N -acyloxazolidinethione; 0.192 mL, 2.00 mmol for N -propionylthiazolidinethione) was added at 0 °C and the mixture was stirred for an additional 10 min. Freshly distilled aldehyde (1.10 mmol) was then added directly to the enolate. The reaction was allowed to stir for 1-2 h followed by addition of half-sat. NH4 Cl. The organic layer was separated and the aqueous layer extracted twice with CH2 Cl2 . The combined organic layers were dried over Na2 SO4 , filtered and concentrated. The initial product mixture was analyzed by 1 H NMR followed by purification by column chromatography.
12a
Crimmins MT.
Choy AL.
J. Org. Chem.
1997,
62:
7548
12b
Crimmins MT.
Choy AL.
J. Am. Chem. Soc.
1999,
121:
5663
12c
Crimmins MT.
Tabet EA.
J. Am. Chem. Soc.
2000,
122:
5473
12d
Crimmins MT.
King BW.
Zuercher WJ.
Choy AL.
J. Org. Chem.
2000,
65:
8499
12e
Crimmins MT.
Emmitte KA.
Choy AL.
Tetrahedron
2002,
58:
1817
13 The use of 2.5 equiv of diisopropylethylamine for N -glycolylimides (compared to the use of 1.1 equiv of diisopropylethylamine forN -propionyl imides) improved the levels of conversion in the aldol reaction.
14
Typical Procedure for Formation of Evans
syn
Adducts from
N
-Glycolylimides. To a dry round-bottom flask under argon was added 1.00 mmol of the appropriate N -acyloxazolidone, N -acyloxazolidinethione, or N -propionylthiazolidinethione, and 10 mL CH2 Cl2 . After cooling to -78 °C, TiCl4 (0.115 mL, 1.05 mmol) was added dropwise and the solution was allowed to stir for 15 min. Diisopropylethylamine (0.434 mL, 2.50 mmol) was added dropwise to the mixture and the solution was allowed to stir for 1-2 h. 1-Methyl-2-pyrrolidinone (0.096 mL, 1.00 mmol) was added at -78 °C and the mixture was stirred for an additional 10 min. Freshly distilled aldehyde (2.00-4.00 mmol) was then added directly to the enolate. The reaction was allowed to stir for 1-2 h at -78 °C and then warmed to -40 °C for 1-2 h followed by addition of half-sat. NH4 Cl. The organic layer was separated and the aqueous layer extracted twice with CH2 Cl2 . The combined organic layers were dried over Na2 SO4 , filtered and concentrated. The initial product mixture was analyzed by 1 H NMR followed by purification by column chromatography.