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DOI: 10.1055/s-0030-1258480
A Useful Modification of the Evans Magnesium Halide Catalyzed anti-Aldol Reaction: Application to Enolizable Aldehydes
Publication History
Publication Date:
09 July 2010 (online)
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Abstract
A practical protocol for use of the magnesium halide catalyzed anti-aldol reaction of an Evans N-acyloxazolidinone with enolizable aldehydes is reported. The yields of anti-aldol adducts for saturated or unsaturated and branched or unbranched aliphatic aldehydes are preparatively useful.
Key words
aldol reaction - aldehydes - halides - catalysis
- Supporting Information for this article is available online:
- Supporting Information
- 1
Mahrwald R. Modern Aldol Reactions Wiley-VCH; Weinheim: 2004. -
2a
Evans DA.Tedrow JS.Shaw JT.Downey CW. J. Am. Chem. Soc. 2002, 124: 392 -
2b
Evans DA.Downey CW.Shaw JT.Tedrow JS. Org. Lett. 2002, 4: 1127 - For anti-aldols with custom auxiliaries, see:
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3a
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3b
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3c
Abiko A.Liu J.Masamune S. J. Am. Chem. Soc. 1997, 119: 2586 -
3d
Kurosu M.Lorca M. J. Org. Chem. 2001, 66: 1205 - For anti-aldols with sultam-based auxiliaries, see:
-
3e
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3f
Oppolzer W.Lienard P. Tetrahedron Lett. 1993, 34: 4321 - For alternative oxazolidinone-based anti-aldols, see:
-
3g
Walker MA.Heathcock CH. J. Org. Chem. 1991, 56: 5747 -
3h
Wessjohann L.Gabriel T. J. Org. Chem. 1997, 62: 3772 -
3i
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3j For organocatalytic methods,
see:
Northrup AB.MacMillan DWC. J. Am. Chem. Soc. 2002, 124: 6798 - For catalytic asymmetric Mukaiyama aldols, see:
-
3k
Yamashita Y.Ishitani H.Shimizu H.Kobayashi S. J. Am. Chem. Soc. 2002, 124: 3292 -
3l
Denmark SE.Wynn T.Beutner GL. J. Am. Chem. Soc. 2002, 124: 13405 - Exceptions are:
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4a
Christoph G.Njardarson JT.Danishefsky SJ. J. Am. Chem. Soc. 2003, 125: 6042 -
4b
Nakamura Y.Kiyota H.Baker BJ.Kuwahara S. Synlett 2005, 635 -
4c
Schnermann MJ.Romero FA.Hwang I.Nakamaru-Ogiso E.Yagi T.Boger DL.
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5a
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5b
This decarboxylative isomerization process was first discovered during these aldol studies.
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-
7a
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References and Notes
General Experimental
Procedure for the
anti
-Aldol Reaction of an
N
-Acyloxazolidinone with an Enolizable Aldehyde
(Synthesis of 2b)
Method A:
To an oven-dried reaction vessel equipped with a stir bar, oxazolidinone 1 (0.100 g, 0.429 mmol), MgCl2 (0.042
g, 0.44 mmol), LiI (0.116 g, 0.866 mmol), EtOAc (0.85 mL), Et3N
(0.30 mL, 2.2 mmol) and TMSCl (0.22 mL, 1.7 mmol) were added sequentially.
After 10 min croton-aldehyde (3b, 107 µL,
1.28 mmol) was diluted to 0.75 mL with EtOAc and added via syringe
pump over 3 h. The reaction mixture was analyzed by GC (90% diastereomeric purity)
and passed through a plug of silica gel using EtOAc as the eluent.
After removing the solvent in vacuo, MeOH (4 mL) and p-TsOH (25 mg) were added. After 15 min desilylation
was complete as judged by TLC. After concentration in vacuo the
desilylated mixture was purified by MPLC (30% EtOAc-70% hexanes)
to give 2b (0.086 g, 66%).
Method B: Same as method A with the following differences:
oxazolidinone 1 (0.200 g, 0.858 mmol),
MgCl2 (0.084 g, 0.88 mmol), LiI (0.228 g, 1.70 mmol),
EtOAc (1.7 mL), Et3N (0.60 mL, 4.3 mmol), and TMSCl (0.44
mL, 3.4 mmol). Crotonaldehyde (3b, 36 µL,
0.42 mmol, 0.49 equiv) in EtOAc (0.21 mL) was added via syringe
pump over 1 h. The desilylated mixture was purified by MPLC (30% EtOAc-70% hexanes)
to give 2b (0.086 g, 66%).
2b:7 ¹H
NMR (500 MHz, CDCl3): δ = 7.32-7.35
(m, 2 H, ArH), 7.23-7.29 (m, 3 H, ArH), 5.78 (ddq, J = 15.5, 6.5, 1.0 Hz, 1 H),
5.54 (ddq, J = 15.0, 7.0, 1.5
Hz, 1 H), 4.69 (dddd, J = 10.0,
7.5, 3.0, 3.0 Hz, 1 H), 4.21 (dd, J = 9.0,
7.0 Hz, 1 H), 4.16 (dd, J = 9.0,
3.0 Hz, 1 H), 3.94 (app p, J = 7.0
Hz, 1 H), 3.29 (dd, J = 13.5,
3.5 Hz, 1 H), 2.78 (dd, J = 13.5,
9.5 Hz, 1 H), 2.54 (s, 1 H, OH), 1.73 (dd, J = 6.5,
1.0 Hz, 3 H), 1.17 (d, J = 6.5
Hz, 3 H). ¹³C NMR (125 MHz, CDCl3): δ = 176.6,
153.7, 135.4, 131.7, 129.7, 129.3, 129.1, 127.5, 75.9, 66.2, 55.7,
43.5, 38.0, 17.9, 14.7. HRMS (ESI): m/z [M + Na+] calcd
for C17H21O4N: 326.1363; found:
326.1361. IR (neat): 3518, 3029, 2976, 2939, 2920, 2883, 1782, 1695, 1502,
1455, 1392, 1349, 1257, 1211, 1103, 1014, 968, 923, 800, 762, 702
cm-¹. TLC: R
f
0.47 (30% EtOAc in hexanes); [α]r.t. 38.5˚ (c = 0.785, CHCl3).