F. Munyemana et al. / Tetrahedron 72 (2016) 420e430
429
only contained t-butyl chloride and amide 1. Yield: 97% (estimated
on the basis of H NMR from the crude mixture). No isobutene was
detected.
3Hþ3H), 1.69 and 1.68 (s, 3Hþ3H), 1.58 (s, 3H), 1.54 and 1.21 (s,
3Hþ3H).
The crude residue was dissolved in 2 mL CH2Cl2 and the solution
was treated at room temperature with 2 mL 1N KOH for 2 h. The
organic phase was washed with water and dried over MgSO4. After
removal of the solvent, lactone 25d was purified by flash chroma-
tography (SiO2, cyclohexaneeethyl acetate 8/2). 1.31 g (52%), Col-
orless crystalline solid, Fus. 89.2 ꢀC, IR (CH2Cl2): 3610 cmꢁ1 (OH),
1765 cmꢁ1 (CO); 1H NMR (200 MHz, CDCl3): 1.80 (s, 1H), 1.46 and
1.44 (s, 3Hþ3H), 1.31 (s, 3H), 1.24 and 1.22 (s, 3Hþ3H); 13C NMR
(50 MHz, CDCl3): 181.4, 88.5, 79.7, 47.6, 26.4, 23.3, 20.2, 19.2. Mass
spectrum (EI): 173 (MþH)þ 100%. Elemental anal.: Calcd: C: 62.77,
H: 9.36; Found: C: 62.80, H: 9.41.
4.5. Chemoselectivity
4.5.1. Competition reactions: general procedure. An equimolecular
solution of the two alcohols was added to a-chloroenamine 2a or
2b at room temperature. In each case the corresponding iso-
butyramide 1a or 1b was obtained quantitatively. The mixtures
were analyzed by GLC. Products were identical with authentic
samples.
4.5.2. Chloro-dehydroxylation of kojic acid 13b. The reaction of
0.968 g (6.8 mmol) of kojic acid with 1 g (7.5 mmol) 2a for 3 h in
5 mL CH2Cl2 yielded quantitatively the corresponding chloride 14b.
1H NMR (200 MHz, acetone-d6): 8.08 (s, 1H), 6.59 (s, 1H), 4.63 (s,
2H); 13C NMR (50 MHz, DMSO-d6): 174 (CO), 162.1, 146.4, 140.5,
113.6, 41.5.
4.6.3. Reaction of benzoin 22c with 2a. Procedure B: 1.444 g
(6.8 mmol) benzoin 22c, 1 g (7.5 mmol) 2a, 7 mL CH2Cl2, 3 h. A 4.26/
1 mixture of iminium salt 24c and chloride 23c was obtained as
shown by 1H NMR. The chloride 23c was identical with an au-
thentic sample: 1H NMR (200 MHz, CDCl3): 7.30e8.00 (m, 10Har),
6.38 (s, CHCl, 1H). Compound 24c was recrystallized from CH2Cl2/
diethylether. 1.16 g (71%), Fus. 160e161 ꢀC; IR (KBr): 3400 cmꢁ1
(OH), 1690 cmꢁ1 (C]Nþ), 1620 cmꢁ1 (C]C).
4.5.3. Reaction of p-nitrophenol with 2a. Procedure B. 0.89 g
(6.4 mmol) p-nitrophenol, 1 mL (7.1 mmol) TMCE 2a in DCM at rt.
Only the corresponding keteniminium chloride 16 was observed by
4.6.4. Reaction of 2-hydroxyisobutyrate with 2a. Procedure B:
0.42 g (3.2 mmol) hydroxyester, 0.47 g (3.5 mmol) 2a, 2 h. A 3/1
mixture of chloride 29 and alkene was obtained as shown by 1H
NMR. The spectral properties were identical with those of authentic
samples. For the compd 29: 1H NMR (200 MHz, CDCl3): 4.20 (q,
J¼7 Hz, 2H, CH2), 1.78 (s, 6H, (CH3)2C), 1.30 (t, J¼7 Hz, CH3CH2). For
alkene: 1H NMR (200 MHz, CDCl3): 6.10 (app q, J¼1 Hz, 1H, HeC¼),
5.56 (app q, J¼1.5 Hz, 1H, HeC¼), 4.20 (q, J¼7 Hz, 2H, CH2CH3), 1.95
(dd, J1¼1.5 Hz, J2¼1, 3H, CH3C]CH2), 1.78 (t, J¼7 Hz, 3H, CH3CH2);
NMR after 2 days at room temperature: 1H NMR (60 MHz):
d 8.3 (d,
2H, CHNO2), 7.9 (d, 2H, NO2CHCH-), 3.9 (s, 3H, N(CH3)2), 3.7 (s, 3H,
N(CH3)2), 1.5 (d, 6H, CH(CH3)2).
4.5.4. Reaction of
(3.2 mmol) -naphthol, 0.5 mL (3.5 mmol) TMCE 2a in DCM for 2 h
at rt. Only the corresponding keteniminium chloride was observed
by NMR. 1H NMR (200 MHz):
7.4e8.1 (m, 7H, Har), 4.0 (s, 3H,
a-naphthol with 2a. Procedure B: 0.464 g
a
d
NCH3), 3.85 (s, 3H, NCH3), 3.38 (sept, J¼7.0 Hz, 1H, CHCH3), 1.41 (d,
J¼7.0 Hz, 6H, CH(CH3)2).
4.6.5. Reaction of methyl mandelate with 2a. Procedure A: 1.13 g
(6.8 mmol) methyl mandelate, 1 g (7.5 mmol) 2a, 3 h. As shown by
1H NMR, a 1.35/1 mixture of iminium salt 31 and chloride 30 was
obtained after 3 h of reaction at room temperature. When reaction
was continued for 12 h, the iminium salt slowly gives the ring-
opening product 32. The same result was obtained if the reaction
was refluxed for 2 h.
4.5.5. Reaction of
(3.2 mmol) -naphthol, 0.5 mL (3.5 mmol) TMCE 2a in DCM for 2 h
at rt. Only the corresponding keteniminium chloride was observed
by NMR. 7.5e8.1 (m, 7H, Har), 3.91 (s, 3H, NCH3), 3.74 (s, 3H, NCH3),
3.46 (sept, J¼7.0 Hz, 1H, CHCH3), 1.45 (d, J¼7.0 Hz, 6H, CH(CH3)2).
b-naphthol with 2a. Procedure B: 0.464 g
b
d
For compd 30: 1H NMR (200 MHz, CDCl3): 7.30e7.50 (m, 5H,
Har), 5.37 (s, 1H, CHCl), 3.76 (s, 3H, CH3O); 13C NMR (50 MHz,
CDCl3): 169.5 (C]O), 136.3 (Cq ar), 129.9 (2CHar), 129.4 (2CHar),
128.5 (CHar), 59.3 (CHCl), 53.7 (COOCH3). IR (CH2Cl2): 1760 cmꢁ1
(COO);
4.6.
a- and b-Hydroxyketones and esters
4.6.1. Reaction of 1-hydroxy-2-butanone 22a with 2a. Procedure A:
0.567 g (6.4 mmol) of 22a, 0.945 g (7.67 mmol) 2a, 7 mL CH2Cl2, 1 h
at rt; ratio 4.6/1 1-chloro-2-butanone 23a/iminium salt 24a mea-
sured by 1H NMR. 1-Chloro-2-butanone 23a 0.445 g (65%) was
purified by distillation (30 ꢀC/13 mmHg) and was found identical
with an authentic sample: 1H NMR (200 MHz, CDCl3): 4.12 (s, 2H),
2.63 (q, J¼7.3 Hz, 2H), 1.12 (t, J¼7.3 Hz, 3H). The minor product 24a
was not purified. The structure was proposed on the basis of its 1H
NMR spectrum and the comparison with the spectroscopic prop-
erties of 24bed. 1H NMR (200 MHz, CDCl3): 4.97 (d, J¼9.7 Hz, 1H),
4.71 (d, J¼9.7 Hz, 1H), 3.61 (s, 3H), 3.50 (s, 3H), 1.68 (s, 3H), 1.44 (q,
J¼7.3 Hz, 2H), 1.43 (s, 3H), 1.09 (t, J¼7.3 Hz, 3H).
For compd 31: 1H NMR (200 MHz, CDCl3): 7.30e7.60 (m, 5H,
Har), 6.70 (s,1H, CHC]O), 3.71 (s, 3H, CH3N]C), 3.68 (s, 3H, CH3N]
C), 2.00 (s, 3H, CH3CC]O), 1.61 (s, 3H, CH3CC]O).
4.6.6. Reaction of 3-hydroxy-ethylbutyrate with 2a. Procedure B:
0.43 g (3.2 mmol) hydroxyester, 0.47 (3.5 mmol) 2a, 4 h. A 9/1
mixture of chloride and alkene was obtained as shown by 1H NMR.
For chloride: 1H NMR (200 MHz, CDCl3): 4.40 (sept, J¼7 Hz, 1H,
CHCl), 4.20 (q, J¼7 Hz, 2H, eCO2CH2CH3), 2.70 (d, J¼7 Hz, 2H,
CHClCH2CO2e), 1.60 (d, J¼7 Hz, 3H, CH3CHCl), 1.30 (t, J¼7 Hz, 3H,
CH3CH2OCO). For alkene: 1H NMR (200 MHz, CDCl3): 6.97 (dxq,
J1¼15.6 Hz, J2¼6.9 Hz, 1H, CH3CH]C), 5.84 (dxq, J1¼15.6 Hz,
J2¼1.7 Hz, 1H, eCOOCH]C), 4.18 (q, J¼7 Hz, 2H, CH3CH2COOe), 1.88
(dxd, J1¼6.9 Hz, J2¼1.7 Hz, 3H, CH3CH]CH), 1.28 (t, J¼7 Hz, 3H,
CH3CH2COOe). 13C NMR (50 MHz, CDCl3): 167.1 (C]O), 144.9
(CH3CH]CH), 123.2 (CH3CH]CH), 60.3 (COOCH2CH3), 18.1
(CH3CH]CH), 14.4 (CH3CH2COOe).
4.6.2. Reaction of 2-methyl-2-hydroxy-3-butanone 22b with
2a. Procedure B: 0.328 g (3.2 mmol) 22b, 0.5 mL (3.5 mmol) 2a, 2 h
in 5 mL CH2Cl2, rt. Products ratio measured by 1H NMR: 11/4.7/1
iminium 24b/a,b-unsaturated ketone/chloride 23b. Both chloride
and unsaturated ketone were distilled off from the reaction mix-
ture. They were identical with authentical samples. 1H NMR 23b
(200 MHz, CDCl3): 2.39 (s, 3H), 1.69 (s, 6H): 1H NMR H2C]CH(CH3)
COCH3 (200 MHz, CDCl3): 5.97 and 5.81 (m, 1Hþ1H), 2.34 (s, 3H),
1.87 (t, J¼1 Hz, 3H). The residue contained amide 1a and iminium
salt 24b. 1H NMR crude 24b (200 MHz, CDCl3): 3.50 and 3.39 (s,
4.6.7. Reaction
of
4-hydroxy-4-methylpentan-2-one
with
2a. Procedure B: 0.37 g (3.2 mmol) kydroxyketone, 0.47 (3.5 mmol)
2a, 2 h. A 2/1 mixture of chloride and alkene was obtained as shown