Subscribe to RSS
DOI: 10.1055/s-0030-1258026
Remarkable [3+2] Annulations of Electron-Rich Olefins with Unstabilized Azomethine Ylides
Publication History
Publication Date:
09 August 2010 (online)
Abstract
Herein we would like to communicate that an unstabilized azomethine ylide generated from commercial trimethylamine N-oxide will undergo a remarkable 1,3-dipolar cycloaddition in good yield with electron-rich and unpolarized olefins. A broad range of substituents on the alkenes are tolerated provided they are compatible with excess LDA. This demonstration of novel reaction scope should encourage others to try trimethylamine N-oxide as an azomethine ylide precursor in the synthesis of challenging 3,4-disubstituted pyrrolidines.
Key words
3,4-disubstituted pyrrolidine - cycloaddition - unstabilized azomethine ylide
-
1a
Lewis JR. Nat. Prod. Rep. 2001, 18: 95 -
1b
O’Hagan D. Nat. Prod. Rep. 2000, 17: 435 - 2
Fache F.Schulz E.Tommasino ML.Lemaire M. Chem. Rev. 2000, 100: 2159 - For select recent examples, see:
-
3a
Fish PV.Andrews MD.Fray MJ.Stobie A.Wakenhut F.Whitlock GA. Bioorg. Med. Chem. Lett. 2009, 19: 2829 -
3b
Fish PV.Fray MJ.Stobie A.Wakenhut F.Whitlock GA. Bioorg. Med. Chem. Lett. 2007, 17: 2022 -
3c
Kohrt JT.Bigge CF.Bryant JW.Casimiro-Garcia A.Chi L.Cody WL.Dahring T.Dudley DA.Filipski KJ.Haarer S.Heemstra R.Janiczek N.Narasimhan L.McClanahan T.Peterson JT.Sahasrabudhe V.Schaum R.Van Huis CA.Welch KM.Zhang E.Leadley RJ.Edmunds JJ. Chem. Biol. Drug Des. 2007, 70: 100 - For recent reviews, see:
-
4a
Coldham I.Hufton R. Chem. Rev. 2005, 105: 2765 -
4b
Pandey G.Banerjee P.Gadre SR. Chem. Rev. 2006, 106: 4484 - 5
Padwa A.Dent W. J. Org. Chem. 1987, 52: 235 - 6
Lown JW. 1,3-Dipolar Cycloaddition Chemistry Vol. 1:Padwa A. Wiley; New York: 1984. Chap. 6. - 7
Beugelmans R.Negron G.Roussi G. J. Chem. Soc., Chem. Commun. 1983, 31 -
8a
Beugelmans R.Benadjila-Iguertsira L.Chastanet J.Negron G.Roussi G. Can. J. Chem. 1985, 63: 725 -
8b
Beugelmans R.Chastanet J.Roussi G. Heterocycles 1987, 26: 3197 -
8c
Beugelmans R.Chastanet J.Roussi G. Heterocycles 1987, 26: 3197 -
10a
De B..DeBernardis JF.Prasad R. Synth. Commun. 1988, 18: 481 -
10b
Negron G.Calderon G.Vazquez F.Lomas L.Cardenas J.Marquez C.Gavino R. Synth. Commun. 2002, 32: 1977 -
10c
Kemperman GJ,Stuk TL, andVan Der Linden JJM. inventors; WO2008003460. - 11
Olofson RA.Martz JT.Senet JP.Piteau M.Malfroot T. J. Org. Chem. 1984, 49: 2081
References and Notes
Representative
Procedure
Commercial LDA (2.5 M in THF, 3.1 mL, 4.7
mmol, 4.5 equiv) was added to a solution of (E)-1,2-dimethoxy-4-styrylbenzene
(250 mg, 1.0 mmol, 1 equiv) and trimethyl-amine N-oxide 4 (117 mg, 1.6 mmol, 1.5 equiv) in anhyd THF
(10 mL) at 0 ˚C. After 1 h, the reaction was quenched with
H2O and extracted with EtOAc. The combined organic layers
were dried (Na2SO4) and concentrated under
reduced pressure. The crude residue was purified by flash chroma-tography
eluting with CH2Cl2-MeOH (95:5) to
give 285 mg (92%) of trans-3,4-disubstituted
pyrrolidine 8 as a yellow oil: ¹H
NMR (400 MHz, CDCl3): δ = 7.26-7.12
(m, 5 H), 6.75-6.70 (m, 2 H), 6.68 (s, 1 H), 3.81 (s, 3
H), 3.78 (s, 3 H), 3.36-3.26 (m, 2 H), 3.12-3.06
(m, 2 H), 2.87-2.80 (m, 2 H), 2.44 (s, 3 H) ppm. LC-MS: m/z = 298.1 [M + 1].
Representative
Procedure
A solution of N-methylpyrrolidine 8 (255 mg, 0.9 mmol) in neat ACE-Cl (3
mL) was irradiated in a microwave reactor at 170 ˚C
for 30 min. MeOH (3 mL) was added to the mixture and thermally refluxed
for an additional 1 h. The crude reaction mixture was purified by
ion exchange on a MP-TsOH column to give 51 mg (21%) of
pyrrolidine 11 as a pale yellow oil: ¹H
NMR (400 MHz, CDCl3): δ = 7.26-7.20
(m, 2 H), 7.18-7.12 (m, 3 H), 6.73-6.70 (m, 1
H), 6.70-6.66 (m, 1 H), 6.62 (d, J = 2.0
Hz, 1 H), 3.79 (s, 3 H), 3.75 (s, 3 H), 3.66-3.54 (m, 2
H), 3.35-3.25 (m, 2 H), 3.24-3.14 (m, 2 H), 2.62
(br s, 1 H) ppm. LC-MS: m/z = 284.0 [M + 1].