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DOI: 10.1055/s-2006-939052
Thiourea-Catalyzed Direct Reductive Amination of Aldehydes
Publikationsverlauf
Publikationsdatum:
14. März 2006 (online)
Abstract
A hydrogen-bond-catalyzed direct reductive amination of aldehydes is reported. The acid- and metal-free process uses thiourea as organocatalyst and the Hantzsch ester for transfer-hydrogenation and allows for the high-yielding synthesis of diverse amines.
Key words
amines - reductions - organocatalysis - hydrogen bonds - aminations
- For reviews, see:
-
1a
Martens J. In Houben-Weyl 4th ed., Vol. E21d:de Meijere A. Thieme; Stuttgart: 1995. p.4199 -
1b
Baxter EW.Reitz AB. Organic Reactions Vol. 59: Wiley; New York: 2002. p.1 -
1c
Gomez S.Peters JA.Maschmeyer T. Adv. Synth. Catal. 2002, 344: 1037 -
1d
Tararov VI.Kadyrov R.Riermeier TH.Fischer C.Börner A. Adv. Synth. Catal. 2004, 346: 561 -
1e
Ohkuma T.Noyori R. In Comprehensive Asymmetric Catalysis 1st Suppl.:Jacobsen EN.Pfaltz A.Yamamoto H. Springer; New York: 2004. -
2a
Ghose AK.Viswanadhan VN.Wendoloski JJ. J. Comb. Chem. 1999, 1: 55 -
2b
Henkel T.Brunne RM.Mueller H.Reichel F. Angew. Chem. Int. Ed. 1999, 38: 643 - For selected recent examples, see:
-
3a
Gross T.Seayad AM.Ahmad M.Beller M. Org. Lett. 2002, 4: 2055 -
3b
Miriyala B.Bhattacharyya S.Williamson JS. Tetrahedron 2004, 60: 1463 -
3c
Itoh T.Nagata K.Miyazaki M.Ishikawa H.Kurihara A.Ohsawa A. Tetrahedron 2004, 60: 6649 -
4a
John RO. In Comprehensive Biological Catalysis Vol 2:Sinnot M. Academic Press; London: 1998. p.173 -
4b
Silverman RB. The Organic Chemistry of Enzyme-Catalyzed Reactions Academic Press; London: 2002. p.428 - 5
Steevens JB.Pandit UK. Tetrahedron 1983, 39: 1395 - 6
Fujii M.Aida T.Yoshihara M.Ohno A. Bull. Chem. Soc. Jpn. 1989, 62: 3845 - 7
Itoh T.Nagata K.Kurihara A.Miyazaki M.Ohsawa A. Tetrahedron Lett. 2002, 43: 3105 - 8
Rueping M.Sugioni E.Azap C.Theissmann T.Bolte M. Org. Lett. 2005, 7: 3781 - 9
Hoffmann S.Seayad AM.List B. Angew. Chem. Int. Ed. 2005, 44: 7424 - 10
Storer RI.Carrera DE.Ni Y.MacMillan DWC. J. Am. Chem. Soc. 2006, 128: 84 - For a review and recent examples on the use of urea and analogues in organocatalysis, see:
-
11a
Berkessel A.Gröger H. Asymmetric Organocatalysis VCH; Weinheim: 2005. -
11b
Yoon TP.Jacobsen EN. Angew. Chem. Int. Ed. 2005, 44: 466 -
11c
Fuerst DE.Jacobsen EN. J. Am. Chem. Soc. 2005, 127: 8964 -
11d
Berkessel A.Cleemann F.Mukherjee S.Müller TN.Lex J. Angew. Chem. Int. Ed. 2005, 44: 807 -
11e
Xu X.Yabuta T.Yuan P.Takemoto Y. Synlett 2006, 137 -
12a
Benzene and CH2Cl2 are as suitable as toluene, while more polar solvents such as dioxane or THF are less efficient. Protic solvents (e.g. MeOH) are of limited applicability.
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12b
Upon extended reaction times, the transformation may also be carried out at r.t.
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14a
The catalyst loading may be reduced to 1 mol% upon extended reaction times (>48 h).
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14b
Under the same reaction conditions but in the absence of thiourea, the product amine is only obtained in low yields proving the vital influence of the organocatalyst.
- 15 This assumption is supported by previous calculations on related thiourea complexes with aldimines and amines:
Vachal P.Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 10012
References and Notes
General Procedure.
A solution of the aldehyde (1a-f, 2.20 mmol) and the amine (2a-g, 2.00 mmol) in toluene (5 mL) is treated with the Hantzsch ester (3, 608 mg, 2.40 mmol), thiourea (4, 15.2 mg, 0.200 mmol) and MS 5 Å (2.0 g). The mixture is stirred 24 h at 70 °C under nitrogen. After filtration over Celite®, the solvent is evaporated and the residue purified by flash chromatography on silica gel using mixtures of PE and EtOAc as eluants to give the product amines (5a-l) in pure form.
All new compounds had spectroscopic data in support of the assigned structures.
Compound 5d: 1H NMR (300 MHz, CDCl3): δ = 3.73 (s, 3 H), 4.27 (s, 2 H), 6.56 (d, J = 9.04 Hz, 2 H), 6.76 (d, J = 9.04 Hz, 2 H), 7.12 (d, J = 8.48 Hz, 1 H), 7.60 (d, J = 10.74 Hz, 1 H), 8.10 (d, J = 2.26 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ = 47.95, 55.80, 114.37, 115.02, 120.26, 123.37, 132.45, 133.56, 136.76, 141.58, 152.66, 154.27. HRMS (ESI): m/z calcd for C14H15N2O4 [M + H]+: 275.1032. Found: 275,1034.
Compound 5k: 1H NMR (300 MHz, CDCl3): δ = 2.54 (s, 3 H), 4.21 (s, 1 H), 4.37 (s, 2 H), 6.71 (d, J = 4.14 Hz, 2 H), 6.82 (d, J = 3.96 Hz 2 H), 7.26-7.36 (m, 5 H). 13C NMR (75 MHz, CDCl3): δ = 26.73, 48.31, 111.82, 118.01, 127.55, 128.77, 129.40, 138.27, 139.89, 148.29, 198.57. HRMS (ESI): m/z calcd for C15H16NO [M + H]+: 226,1232. Found: 226,1233.
Compound 5l: 1H NMR (400 MHz, CDCl3): δ = 3.52 (s, 2 H), 4.31 (s, 2 H), 6.60 (d, J = 8.65 Hz, 2 H), 7.07 (d, J = 8.65 Hz, 2 H), 7.26-7.34 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ = 40.00, 48.47, 113.12, 122.18, 127.54, 128.69, 130.24, 139.24, 139.35, 147.43, 176.85. HRMS (ESI): m/z calcd for C15H16NO2 [M + H]+: 242.1181. Found: 242.1178.