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DOI: 10.1055/s-0029-1218282
Organocatalytic Asymmetric Triple Domino Reactions of Nitromethane with α,β-Unsaturated Aldehydes
Publication History
Publication Date:
08 October 2009 (online)
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Abstract
An organocatalytic asymmetric multicomponent domino reaction employing the bulk chemical nitromethane and α,β-unsaturated aldehydes as substrates is described. The new triple cascade reaction based on two subsequent Michael additions and an intramolecular aldol condensation provides an atom-economic entry to diastereo- and enantiomerically pure 5-nitrocyclohexene carbaldehydes after flash chromatography.
Key words
domino reaction - organocatalysis - Michael addition - nitroalkane - aldol condensation
- 1 For a recent review on nitroalkane
additions to α,β-unsaturated carbonyl compounds,
see:
Ballini B.Bosica G.Fiorini G.Palmieri A.Petrini M. Chem. Rev. 2005, 105: 933 - For selected examples, see:
-
2a
Hanessian S.Pham V. Org. Lett. 2000, 2: 2975 -
2b
Corey EJ.Zhang F.-Y. Org. Lett. 2000, 2: 4257 -
2c
Halland N.Hazell RG.Jørgensen KA. J. Org. Chem. 2002, 67: 8331 -
2d
Tsogoeva SB.Jagtap SB. Synlett 2004, 2624 -
2e
Mitchell CET.Brenner SE.Ley SV. Chem. Commun. 2005, 5346 -
2f
Prieto A.Halland N.Jørgensen KA. Org. Lett. 2005, 7: 3897 -
2g
Vakulya B.Varga S.Csámpai A.Soós T. Org. Lett. 2005, 7: 1967 -
2h
Ooi T.Takada S.Fujioka S.Maruoka K. Org. Lett. 2005, 7: 5143 -
2i
Hanessian S.Shao Z.Warrier JS. Org. Lett. 2006, 8: 4787 -
2j
Enders D.Narine AA.Benninghaus TR.Raabe G. Synlett 2007, 1667 -
2k
Zu L.Xie H.Li H.Wang J.Wang W. Adv. Synth. Catal. 2007, 349: 2660 -
2l
Gotoh H.Ishikawa H.Hayashi Y. Org. Lett. 2007, 9: 5307 -
2m
Hojabri L.Hartikka A.Moghaddam FM.Arvidsson PI. Adv. Synth. Catal. 2007, 349: 740 -
2n
Wang Y.Li P.Liang X.Zhang TY.Ye J. Chem. Commun. 2008, 1232 -
2o
Li P.Wang Y.Liang X.Ye J. Chem. Commun. 2008, 3302 -
2p
Enders D.Wang C.Bats JW. Synlett 2009, 1777 -
2q
Zhong S.Chen Y.Petersen JL.Akhmedov NG.Shi X. Angew. Chem. Int. Ed. 2009, 48: 1279 -
2r
Mei K.Jin M.Zhang S.Li P.Liu W.Chen X.Xue F.Duan W.Wang W. Org. Lett. 2009, 11: 2864 -
2s
Gotoh H.Okamura D.Ishikawa H.Hayashi Y. Org. Lett. 2009, 11: 4056 -
2t
Chen Y.Zhong C.Sun X.Akhmedov NG.Petersen JL.Shi X. Chem. Commun. 2009, 5150 - For recent reviews on organocatalysis, see:
-
3a
Berkessel A.Gröger H. Asymmetric Organacatalysis Wiley-VCH; Weinheim: 2005. -
3b
Seayad J.List B. Org. Biomol. Chem. 2005, 3: 719 -
3c
Marigo M.Jørgensen KA. Chem. Commun. 2006, 2001 -
3d
List B. Chem. Commun. 2006, 819 -
3e
Lelais G.MacMillan DWC. Aldrichimica Acta 2006, 39: 79 - 3f Special issue on organocatalysis: Chem. Rev. 2007, 107: 5413
-
3g
Dalko PI. Enantioselective Organocatalysis, Reactions and Experimental Procedures Wiley-VCH; Weinheim: 2007. -
3h
de Figueiredo RM.Christmann M. Eur. J. Org. Chem. 2007, 2575 -
3i
Dondoni A.Massi A. Angew. Chem. Int. Ed. 2008, 47: 4638 -
3j
Melchiorre P.Marigo M.Carlone A.Bartoli G. Angew. Chem. Int. Ed. 2008, 47: 6138 -
3k
Yu X.Wang W. Org. Biomol. Chem. 2008, 6: 2037 -
3l
Bella M.Gasperi T. Synthesis 2009, 1583 -
3m
Bertelsen S.Jørgensen KA. Chem. Soc. Rev. 2009, 38: 2178 - For reviews on domino reactions, see:
-
4a
Tietze LF. Chem. Rev. 1996, 96: 115 -
4b
Tietze LF.Brasche G.Gericke K. Domino Reactions in Organic Synthesis Wiley-VCH; Weinheim: 2006. -
4c
Pellissier H. Tetrahedron 2006, 62: 1619 -
4d
Pellissier H. Tetrahedron 2006, 62: 2143 -
4e
Nicolaou KC.Edmonds DJ.Bulger PG. Angew. Chem. Int. Ed. 2006, 45: 7134 -
4f
Chapman CJ.Frost CG. Synthesis 2007, 1 -
4g
Poulin J.Grisé-Bard CM.Barriault L. Chem. Soc. Rev. 2009, in press; DOI: 10.1039/b819798a -
5a
Enders D.Hüttl MRM.Grondal C.Raabe G. Nature (London) 2006, 441: 861 -
5b
Enders D.Hüttl MRM.Runsink J.Raabe G.Wendt B. Angew. Chem. Int. Ed. 2007, 46: 467 -
5c
Enders D.Hüttl MRM.Raabe G.Bats JW. Adv. Synth. Catal. 2008, 350: 267 - For reviews on organocatalytic domino reactions, see:
-
6a
Enders D.Grondal C.Hüttl MRM. Angew. Chem. Int. Ed. 2007, 46: 1570 -
6b
Yu X.Wang W. Org. Biomol. Chem. 2008, 6: 2037 - 7
Carlone A.Cabrera S.Marigo M.Jørgensen KA. Angew. Chem. Int. Ed. 2007, 46: 1101 - 8
Battistuzzi G.Cacchi S.Fabrizi G. Org. Lett. 2003, 5: 777 - 11
Trost BM. Acc. Chem. Res. 2002, 35: 695
References and Notes
CCDC-743470 (3a) contains the supplementary crystallographic data for this paper. More data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www. ccdc.cam.ac.uk/data_request/cif.
10
General Procedure
In
an ordinary vial equipped with a magnetic stirring bar, the α,β-unsaturated
aldehyde 1 (2.2 mmol, 2.2 equiv) was dissolved
in CHCl3 (1 mL). The catalyst (S)-2 (0.2 mmol, 0.2 equiv) and nitromethane
(1 mmol, 1 equiv) were added to the solution. The vial was sealed,
and the mixture was stirred for 20 h at r.t. The crude reaction
mixture was diluted in CH2Cl2, washed with
H2O, and dried over MgSO4. After concentration,
the crude product was purified by flash chromatography (silica gel,
pentane-EtOAc). All new compounds gave satisfactory spectroscopic
and analytical data. As a typical example, the data of the compound 3a are given.
(4
S
,5
R
,6
R
)-5-Nitro-4,6-diphenylcyclohex-1-ene carbaldehyde
(3a, Figure 2)
Isolated as a yellow solid (202 mg,
65%). The ee (>99%) was determined by
HPLC on a chiral stationary phase [Chiralcel OD; n-heptane-i-PrOH
(8:2); 1.0 mL/min, t
R = 9.93
min(major), 18.25 min (minor, based on the racemic mixture)];
mp 108 ˚C; [α]D
²0 -123
(c 1.1, CHCl3). IR (ATR):
3060, 2807, 2718, 2323, 2115, 1684, 1653, 1547, 1494, 1450, 1410,
1366, 1247, 1162, 1078, 946 cm-¹. ¹H NMR
(400 MHz, CDCl3): δ = 2.89
(ddd, J = 5.2,
5.2, 20.0 Hz, 1 H, H3); 3.25 (dddd, J = 2.4,
11.2, 11.2, 20.0 Hz, 1 H, H3
′), 3.35-3.40
(m, 1 H, H4), 4.32-4.38 (m, 1 H, H6);
4.96 (dd, J = 1.9,
3.0 Hz, 1 H, H5), 7.03-7.07 (m, 2 H, HPh-
para
), 7.22-7.38 (m, 9
H, HPh and H2), 9.57 (s, 1 H, HCHO). ¹³C NMR
(100 MHz, CDCl3): δ = 28.0
(C3), 37.3 (C4), 43.2 (C6), 91.3
(C5), 127.3 (CH), 128.0 (CH), 128.9 (CH), 129.2 (CH), 137.9,
138.0, 138.8 (CPh, C1), 150.4 (C2),
191.65 (CHO). HRMS (EI): m/z calcd
for C19H1703N1: 307.1203;
found: 307.1208.
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Figure 2