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
References
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
7 The tetrazole is not soluble in neat ketone.
8
General Procedure : N -PMP-protected α-imino ethyl glyoxalate (93.5 mg, 0.5 mmol) was dissolved in anhydrous CH2 Cl2 (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. NH4 Cl 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.
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
10 Determined 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
11 In 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