References
1
Bertus P.
Szymoniak J.
Chem. Commun.
2001,
1792
2
Bertus P.
Szymoniak J.
J. Org. Chem.
2002,
67:
3965
3a
Kulinkovich OG.
Sviridov SV.
Vasilevsky DA.
Pritytskaja TS.
Russ. J. Org. Chem.
1989,
25:
2027
3b
Kulinkovich OG.
Sviridov SV.
Vasilevsky DA.
Synthesis
1991,
234
For reviews, see:
4a
de Meijere A.
Kozhushkov SI.
Savchenko AI. In
Titanium and Zirconium
in Organic Synthesis
Marek I.
Wiley-VCH;
Weinheim:
2002.
p.390
4b
Kulinkovich OG.
de Meijere A.
Chem.
Rev.
2000,
100:
2789
5
Lee J.
Kim YG.
Bae JG.
Cha JK.
J. Org. Chem.
1996,
61:
4878
6a
Chaplinski V.
de Meijere A.
Angew.
Chem., Int. Ed. Engl.
1996,
35:
413
6b
Lee J.
Cha JK.
J. Org. Chem.
1997,
62:
1584
7 Carboxylic esters have been demonstrated
to be generally more reactive towards the cyclopropanation reaction
than the corresponding amides, see: Cho SY.
Lee J.
Lammi RK.
Cha JK.
J. Org. Chem.
1997,
62:
8235
8 Under the same cyclopropanation conditions,
the ester 2 alone or the amide 3 alone give cyclopropanol 5 (66% yield) or
cyclopropylamine 6 (40%) respectively,
irrespective of the addition of BF3·OEt2.
9 No cyclopropane-containing product
was obtained from ethyl cyanoacetate, probably due to the presence
of acidic hydrogens.
10 Typical procedure for the synthesis
of 8, 10, 12 and 14: Ethyl 1′-aminobicyclopropyl-1-carboxylate 10: To a solution of nitrile 9 (139 mg, 1 mmol) and Ti(i-PrO)4 (0.33
mL, 1.1 mmol) in anhydrous Et2O (5 mL), was added dropwise
at room temperature a solution of EtMgBr in Et2O (2 mmol). After
the mixture was stirred for 1 h, BF3·OEt2 (0.25
mL, 2 mmol) was added. After additional stirring for 30 min, water (1
mL) was added, followed by 10% aq HCl (10 mL) and CH2Cl2 (20
mL). A 10% aq NaOH 10% solution was added to the
resulting clear mixture until the pH became basic. The product was
extracted with CH2Cl2 (2 × 20 mL).
The combined organic extracts were dried (Na2SO4).
After evaporation of the solvent, the product was purified by flash chromatography
on silica gel (Et2O, then acetone) to afford 83 mg (49%)
of 10 as a pale yellow oil. IR (KBr): 3373, 1719,
1311 cm-1. 1H NMR
(500 MHz, CDCl3): δ = 0.35-0.39
(m, 2 H), 0.60-0.69 (m, 4 H), 1.15-1.21 (m, 2
H), 1.26 (t, J = 7.1 Hz, 3 H),
2.15 (s, 2 H), 4.15 (q, J = 7.1
Hz, 2 H). 13C NMR (126 MHz, CDCl3): δ = 13.1,
14.2, 14.7, 30.5, 34.9, 60.5, 174.8. MS (EI, 70 eV), m/z (%): 169 (4, M+),154 (18),
140 (34), 123 (60), 112 (78), 94 (100).
For recent reviews on the use and
preparation of β-amino acids, see:
11a
Steer DA.
Lew RA.
Perlmutter P.
Smith AI.
Aguilar MI.
Curr. Med. Chem.
2002,
9:
811
11b
Abele S.
Seebach D.
Eur. J. Org. Chem.
2000,
1
12 Typical procedure for the synthesis
of 16, 18, 20 and 22: 4-Azaspiro[2.5]octan-5-one 18: To a solution of nitrile 17 (141 mg, 1 mmol) and Ti(i-PrO)4 (0.33 mL, 1.1 mmol)
in anhydrous Et2O (5 mL), was added dropwise at room temperature
a solution of EtMgBr in Et2O (2 mmol). After the mixture
was stirred for 1 h, water (1 mL) was added, followed by CH2Cl2 (20
mL). The resulting precipitate was removed and washed with CH2Cl2 (2 × 10
mL). The combined organic extracts were dried (Na2SO4).
After evaporation of the solvent, the product was purified by flash chromatography
on silica gel (Et2O, then Et2O-MeOH, 95:5)
to afford 80 mg (63%) of 18 as
a white solid, mp 124-125 °C. IR (KBr): 3183,
3058, 2951, 1655, 1404 cm-1. 1H NMR
(250 MHz, CDCl3): δ = 0.58-0.66
(m, 2 H), 0.69-0.76 (m, 2 H), 1.61-1.67 (m, 2
H), 1.83-1.95 (m, 2 H), 2.37 (t,
J = 6.7
Hz, 2 H), 7.08 (s, 1 H). 13C NMR (63
MHz, CDCl3): δ = 12.8, 20.0, 30.9,
31.1, 35.8, 173.5. MS (EI, 70 eV), m/z (%):
125 (38, M+), 96 (48), 82 (100).
13 These spirocyclopropanelactams cannot
be directly prepared from cyclic imides using the same procedure
(Grignard reagent and titanium isopropoxide), since the resulting titanaoxacyclopentanes
do not lead to cyclopropane formation. See: Lee J.
Ha JD.
Cha JK.
J.
Am. Chem. Soc.
1997,
119:
8127
14 The spirolactam 16,
being a γ-aminobutyric acid (GABA) analogue, has already
been prepared, in several steps. See: Kordes M.
Winsel H.
de Meijere A.
Eur.
J. Org. Chem.
2000,
3235
