References
<A NAME="RS02803ST-1A">1a</A>
Eaton PE.
Zhang MX.
Angew.
Chem. Int. Ed.
2002.
41:
p.2169
<A NAME="RS02803ST-1B">1b</A> See also:
Eaton PE.
Lee CH.
Xiong Y.
J. Am. Chem. Soc.
1989,
111:
8016
<A NAME="RS02803ST-1C">1c</A>
Eaton PE.
Xiong Y.
Lee CH.
J. Chin. Chem. Soc.
1991,
38:
303
<A NAME="RS02803ST-2">2</A> The activating/stabilizing
carboxamido group need not be on the β-carbon, see:
Eaton PE.
Lukin K.
J.
Am. Chem. Soc.
1993,
115:
11370
<A NAME="RS02803ST-3">3</A>
Streitwieser A.
Caldwell RA.
Young WR.
J. Am. Chem. Soc.
1969,
91:
529
<A NAME="RS02803ST-4">4</A>
We assign the liganding interaction
shown by analogy to that seen in a cyclopropyl example for which
we have a single crystal X-ray structure: Eaton, P. E.; Zhang, M.
X.; Steele, I., unpublished results
<A NAME="RS02803ST-5">5</A>
Typical Procedure. Dry
diisopropylamine (202 mg, 2.0 mmol) was added dropwise to a stirred
1 M solution of Bu2Mg in heptanes (Aldrich, 2.0 mL, 2.0
mmol) at 0 °C. The mixture was stirred at r.t. for 1.5
h to give a pale yellow BuMgN(i-Pr)2 solution.
Amide 3 (99 mg, 0.5 mmol) in THF (1.5 mL)
was added at r.t. to the base solution so made. The resulting pale
yellow solution was taken to reflux (73 °C, bath at 85 °C)
for 4 h. Afterwards, the solution was cooled to r.t. and added to
I2 (1 g, 4 mmol) in THF (5 mL) at 0 °C. The mixture
was stirred at r.t. for 1.5 h then quenched with aq 10% HCl
(5 mL), extracted with CHCl3 (3 × 10
mL) and washed with aq sat. (NH4)2SO4 (10
mL). The extract was washed with an aq 10% Na2S2O3 (10
mL), then again with aq sat. (NH4)2SO4 (2 × 10
mL), dried over Na2SO4 and concentrated at
r.t. in vacuo. The residual brown liquid was chromatographed (silica
gel, CH2Cl2) to give 7 (124
mg, 77%) as a colorless solid: mp 119-120 °C. 1H
NMR (400 MHz, CDCl3): δ = 4.96 (dd, J = 10 and
9 Hz, 1 H), 3.73 (sept, J = 7
Hz, 1 H), 3.27 (sept, J = 7
Hz, 1 H), 2.48 (m, 1 H), 2.31-2.42 (m, 2 H), 2.02 (m, 1
H), 1.47 (s, 3 H), 1.39 (d, J = 7
Hz, 3 H), 1.38 (d, J = 7
Hz, 3 H), 1.17 (d, J = 7
Hz, 3 H), 1.15 (d, J = 7
Hz, 3 H). 13C NMR (100 MHz): δ = 174.1, 49.7,
47.9, 46.0, 32.6, 28.8, 28.1, 25.7, 20.7, 20.4., Anal. Calcd for
C12H22INO: C, 44.59; H, 6.86; N, 4.33. Found:
C, 44.97; H, 6.79; N, 4.36. The epimer of 7 was
eluted somewhat later from the column: mp 109-110 °C. 1H
NMR (400 MHz, CDCl3): δ = 4.21 (dd, J = 6.0 and
5.6 Hz, 1 H), 3.45 (sept, J = 6.4
Hz, 1 H), 3.29 (sept, J = 6.8
Hz, 1 H), 3.17 (dd, J = 20.0
and 11.2 Hz, 1 H), 2.85-2.75 (m, 1 H), 2.09 (m, 1 H), 1.64-1.57
(m, 1 H), 1.53 (s, 3 H), 1.40 (d, J = 6.8
Hz, 3 H), 1.38 (d, J = 6.8
Hz, 3 H), 1.35 (d, J = 6.4
Hz, 3 H), 1.18 (d, J = 6.4
Hz, 3 H). 13C NMR (100 MHz): δ = 173.2,
52.0, 48.3, 46.1, 30.8, 30.2, 29.2, 22.2, 21.6, 21.1, 20.5, 20.2.
MS (ES): 324.0 [M + 1].
Crystallographic data have been
deposited with the Cambridge Crystallographic Data Centre, e-mail: deposit@ccde.cam.ac.uk,
as supplementary publications numbered:
<A NAME="RS02803ST-6A">6a</A>
206444;
<A NAME="RS02803ST-6B">6b</A>
173571;
<A NAME="RS02803ST-6C">6c</A>
209582 (racemate);
<A NAME="RS02803ST-6D">6d</A>
205769.
<A NAME="RS02803ST-7">7</A> Remarkably little is known about
what happens at the magnesiated carbon during Grignard reactions
with {E+}. See:
Gawley RE. In
Grignard
Reagents. New Developments
Richey HG.
Wiley;
Chichester:
2000.
p.139
<A NAME="RS02803ST-8">8</A>
We estimate that we would have seen
in the NMR spectra of the crudes any other isomer present in >10% yield.
<A NAME="RS02803ST-9">9</A>
Bu2Mg as supplied commercially
(Aldrich) has a mix of
n-butyl
and sec-butyl groups. Thus, two bases
result from reaction with HN(i-Pr)2: n-BuMgN(i-Pr)2 and sec-BuMgN(i-Pr). We
have made each separately and have found only small differences
in their ability to deprotonate/magnesiate 3.
<A NAME="RS02803ST-10">10</A>
Zhang MX.
Komiya N.
Eaton PE.
224th
ACS National Meeting, Boston
2002.
p.341-ORGN
<A NAME="RS02803ST-11">11</A>
Best value at present for neopentane:cyclohexane
relative kinetic acidity is 8.2:1 (per hydrogen) obtained using CsCHA
at 50 °C. Private Communication, Prof. A. Streitwieser,
March 4, 2003.