RSS-Feed abonnieren
DOI: 10.1055/s-2004-817745
5-Pyrrolidin-2-yltetrazole: A New, Catalytic, More Soluble Alternative to Proline in an Organocatalytic Asymmetric Mannich-type Reaction
Publikationsverlauf
Publikationsdatum:
06. Februar 2004 (online)
![](https://www.thieme-connect.de/media/synlett/200403/lookinside/thumbnails/10.1055-s-2004-817745-1.jpg)
Abstract
A Mannich-type addition of ketones to N-PMP protected α-imino ethyl glyoxalate is catalyzed by a new proline analogue, 5-pyrrolidin-2-yltetrazole 1. The new organocatalyst has significant advantage over its parent in that it can be used in non-polar solvents without loss of enantioselectivity.
Key words
asymmetric - Mannich - organocatalysis - proline - tetrazole
-
1a
Dalko PI.Moisan L. Angew. Chem. Int. Ed. 2001, 40: 3726 ; and references therein -
1b
Brown SP.Brochu MP.Sinz CJ.MacMillan DWC. J. Am. Chem. Soc. 2003, 125: 10808 -
1c
Pidathala C.Hoang L.Vignola N.List B. Angew. Chem. Int. Ed. 2003, 42: 2785 - 2
List B. Tetrahedron 2002, 58: 5573 -
3a
Hajos ZG.Parrish DR. J. Org. Chem. 1974, 39: 1615 -
3b
List B.Pojarliev P.Castello C. Org. Lett. 2001, 3: 573 -
3c
Szollosi G.Lonfon G.Balaspiri L.Somlai C.Bartok M. Chirality 2003, 15: S90 -
3d
Northrup AB.MacMillan DWC. J. Am. Chem. Soc. 2002, 124: 6798 -
4a
Rajagopal D.Narayanan R.Swaminathan S. Tetrahedron Lett. 2001, 42: 4887 -
4b
Bui T.Barbas CF. Tetrahedron Lett. 2000, 41: 6951 -
5a
Córdova A.Notz W.Zhong G.Betancort JM.Barbas CF. J. Am. Chem. Soc. 2002, 124: 1842 -
5b
Pojarliev P.Biller WT.Martin HJ.List B. Synlett 2003, 1903 -
5c
Chowdari NS.Ramachary DB.Barbas CF. Synlett 2003, 1906 -
5d
Córdova A.Watanabe S.-i.Tanaka F.Notz W.Barbas CF. J. Am. Chem. Soc. 2002, 124: 1866 -
5e
Notz W.Tanaka F.Watanabe S.-i.Chowdari NS.Turner JM.Thayumanavan R.Barbas CF. J. Org. Chem. 2003, 68: 9624 -
5f
Itoh T.Yokoya M.Miyauchi K.Nagata K.Ohsawa A. Org. Lett. 2003, 5: 4301 - 6
Almquist RG.Chao W.-R.Jennings-White C. J. Med. Chem. 1985, 28: 1067 -
9a
Bahmanyar S.Houk KN. J. Am. Chem. Soc. 2001, 123: 12911 -
9b
Bahmanyar S.Houk KN. J. Am. Chem. Soc. 2001, 123: 11273 -
9c
Bahmanyar S.Houk KN.Martin HJ.List B. J. Am. Chem. Soc. 2003, 125: 2475 -
9d
Hoang L.Bahmanyar S.Houk KN.List B. J. Am. Chem. Soc. 2003, 125: 16
References
The tetrazole is not soluble in neat ketone.
8General Procedure: N-PMP-protected α-imino ethyl glyoxalate (93.5 mg, 0.5 mmol) was dissolved in anhydrous CH2Cl2 (4 mL). Carbonyl-containing compound (1 mL, 20 vol%) was added to this solution followed by 5-pyrrolidin-2-yltetrazole (3.5 mg, 5 mol%) and the resulting mixture stirred under argon for 2-24 h. After this time, the mixture was quenched with sat. NH4Cl solution (10 mL) and the aqueous layer extracted with EtOAc (2 × 25 mL). The combined organic layers were dried (MgSO4), filtered and evaporated under reduced pressure to give a residue which was further purified by column chromatography using varying mixtures of EtOAc and petroleum ether 40-60 as eluent.
10Determined by chiral HPLC (3): Chiralcel AS 0.7 mLmin-1, 6% 2-propanol: 94% hexane; tR(major) = 18 min, tR(minor) = 24 min. 5: Chiralcel AS 0.7 mLmin-1 94% hexane: 6% 2-propanol; tR(major) = 14 min, tR(minor) = 16 min. 6: Chiralcel AS 1 mLmin-1 85% hexane: 15% 2-propanol; tR(major) = 16 min, tR(minor) = 22 min. 7: Chiralcel OD 1 mLmin-1, 5% 2-propanol: 95% hexane; tR(major) = 13.5 min, tR(minor) = 19 min. 9 (lactone): Chiralcel AS 0.7 mLmin-1 94% hexane: 6% 2-propanol; tR(minor) = 43 min, tR(major) = 57 min. For retention times of 2, 4 and 8 see ref. 5a
11In order to obtain separation on HPLC, the aldehyde was converted to the lactone by reduction with sodium borohydride (Scheme [3] ) before chromatography to avoid epimerization. This represents a good route to enantiopure functionalized 1-amino-2-alkyl-δ-lactones.
Scheme 3