Abstract
A range of structurally and functionally varied enantiopure cyclic
and bicyclic guanidines has been prepared and evaluated in the enantioselective
epoxidation of 3-tert -butoxycarbonylamino-4,4-dimethoxycyclohexa-2,5-dien-1-one 1 using tert -butylhydroperoxide.
Encouraging enantiomeric excesses were observed (up to 60%).
Low enantiomeric excesses were also observed with 2-methylnaphthoquinone
and trans -chalcone.
Key words
enantioselective - epoxidation - enones - guanidines - stereoselectivity
References
1 For a review see: Porter MJ.
Skidmore J.
Chem.
Commun.
2000,
1215
2
McManus JC.
Carey JS.
Taylor RJK.
Synlett
2003,
365
3
Macdonald G.
Alcaraz L.
Lewis NJ.
Taylor RJK.
Tetrahedron
Lett.
1998,
39:
5433
4
Dwyer CL.
Gill CD.
Ichihara O.
Taylor RJK.
Synlett
2000,
704
5a
Genski T.
Macdonald G.
Wei X.
Lewis N.
Taylor RJK.
Synlett
1999,
795
5b
Genski T.
Macdonald G.
Wei X.
Lewis N.
Taylor RJK.
Arkivoc
2000,
1:
266
6
Alcaraz L.
Macdonald G.
Ragot J.
Lewis NJ.
Taylor RJK.
Tetrahedron
1999,
55:
3707 ; and references therein
7
Baker TJ.
Tomioka M.
Goodman M.
Org.
Synth.
2000,
78:
91
8 All new compounds were fully characterised
by 1 H NMR, 13 C
NMR and IR, plus HRMS or elemental analysis.
Preparation
of 6b. HCl salt:
9a (R )-(-)-2-Phenylglycinol (189
mg, 1.38 mmol) was added to a solution of di-tert -butyl-2-[(trifluoromethanesulfonyl)imino]dihydro-1,3(2H ,4H )-pyrimidinecarboxylate 10 (300 mg, 0.69 mmol) and diisopropyl(ethyl)amine
(0.24 cm3 , 1.38 mmol) in CH2 Cl2 (4
cm3 ), under a nitrogen atmosphere. The solution was
stirred at r.t. for 18 h before the solvent was removed under reduced
pressure and the residue purified by flash silica chromatography
(CH2 Cl2 :MeOH, 50:1) to afford di-tert -butyl-2-[(1R )-2-hydroxy-1-phenylethylimino]dihydro-1,3(2H ,4H )-pyrimidinecarboxylate 11 (208 mg, 71%) as a clear gum, [α]D
20 +18.7
(c 1.25, CHCl3 ) which was
fully characterised.
9b The Boc-protected guanidine 11 (200 mg, 0.48 mmol) was dissolved in
approx. 3 M anhyd. methanolic HCl (20 cm3 ) and
was stirred at r.t., under nitrogen, for 18 h. The solvent was then
removed under reduced pressure to afford N -[(1S )-1-phenyl-2-hydroxyethyl]-N -tetrahydro-2(1H )-pyrimidinylideneaminehydrochloride 6b . HCl quantitatively (124 mg) as a gum, [α]D
20 -40.9
(c 1.0, MeOH). IR(neat): νmax = 3365
(OH), 3029 and 2096 (CH), 1695 (CN3 ) cm-1 .
MS (CI): m/z = 220
(100) [MH+ ], 202 (21), 138
(27), 100 (25), 75 (31). HRMS (CI): Calcd for C12 H18 N3 O:
220.1450. Found: [MH+ ]: 220.1456
(-2.7 ppm error), which gave consistent 1 H
and 13 C NMR spectra.
10a
Isobe T.
Ishikawa T.
J.
Org. Chem.
1999,
64:
6984
10b
Isobe T.
Fukuda K.
Ishikawa T.
Tetrahedron: Asymmetry
1998,
9:
1729
11 Rapid hydrolysis to DMPU occurred;
a one-pot variant was also unsuccessful.
12a
Echavarren A.
Galán A.
de Mendoza J.
Salmeron A.
Helv.
Chim. Acta
1988,
71:
685
12b
Kurzmeier H.
Schmidtchen FP.
J. Org. Chem.
1990,
55:
3749
12c
Gleich A.
Schmidtchen FP.
Chem. Ber.
1988,
71:
685
13 Chiral HPLC was carried out using
a Chiralcel OJ column (25 cm × 4.6 mm)
with hexane-isopropanol (98:2) as eluent at a flow rate
of 1 mL/min and detection at 276 nm.
Michael Additions:
14a
Ishikawa T.
Araki Y.
Kumamoto T.
Seki H.
Fukuda K.
Isobe T.
Chem. Commun.
2001,
245 ;
and references therein
14b
Howard-Jones A.
Murphy PJ.
Thomas DA.
Caulkett PWR.
J.
Org. Chem.
1999,
64:
1039
14c
Ma K.
Cheng K.
Tetrahedron: Asymmetry
1999,
10:
713
15a Strecker
Synthesis: Corey EJ.
Grogan MJ.
Org. Lett.
1999,
1:
157
15b Henry Reaction: Chinchilla R.
Nájera C.
Sánchez-Agulló P.
Tetrahedron: Asymmetry
1994,
5:
1393