5318
J. L. Lukkarila et al. / Tetrahedron Letters 45 (2004) 5317–5319
HO
HO
O
N
i
X
ii
iii
1
O
O
O
OtBu
OtBu
OtBu
3
4
6
X = HgOAc
X = HgBr
X = H
5
Scheme 1. Reagents and conditions: (i) H
chloride, 5–25 °C.
2
O, Hg(OAc)
2
. (ii) DMF, TEMPO, 5 °C; O
2
, then NaBH
3
CN, 2 h. (iii) CH
2
Cl
2
, pyridine, 5 °C; then benzoyl
2
13
the carbonyl group, which would direct the mercuric
acetate to the more highly substituted carbon of
the double bond in the substrate, giving the desired
J
HgH ¼ 337 Hz, 1H2); 2.05 (s, 3H7); 1.47 (s, 9H5).
C
2
NMR (20 °C): d 177.50 (C6); 173.59 ( JHgC ¼ 118 Hz,
2
C3); 82.00 (C4); 61.13 ( J
¼ 107 Hz, C1); 49.48
HgC
9
1
anti-Markovnikov addition product. In fact, the regio-
selectivity of the oxymercuration of t-BuA yielding 3
( JHgC ¼ 1585 Hz, C2); 28.17 (3C5); 22.93 (C7).
1
was greater than 95%, as determined by H NMR.
13,14
4. General procedure for the synthesis of 1
Initially, the mercuric acetate intermediate 3 was con-
verted into the corresponding bromomercury(II) deriv-
ative (4) with KBr, followed by oxidative demercuration
TEMPO (7.55 g, 48 mmol), 3 (4.82 g, 12 mmol) and
DMF (25 mL) were combined in a three-necked round
bottom flask fitted with a sintered glass bubbler and
thermometer. The solution was cooled to 5 °C, bubbled
10
2 4
with O and NaBH in the presence of TEMPO.
Under a variety of reaction conditions, which included
changes in the reaction temperature, the order of addi-
tion of the reagents and the amounts of the various
reagents, the major product was always the reduced
compound 6, with only trace amounts of the desired
with oxygen for 15 min and NaBH CN (2.27 g,
3
3
6 mmol) was then added. The reaction mixture was
stirred for 2 h, after which it was poured into diethyl
ether (50 mL). The resulting mixture was filtered
through Celite to remove the mercury precipitate and
the filtrate evaporated to dryness. The crude mixture
containing 5 was dissolved in CH Cl (80 mL), pyridine
11
nitroxide-trapped product 5. LiBH4 again provided
only the reduced product 6. However, NaBH CN
proved to be a more effective reagent. The reaction of
3
2
2
was added (11.5 mL) and the solution cooled to 5 °C.
Benzoyl chloride (7.8 mL, 43 mmol) was added dropwise
via a dropping funnel over 5 min. The solution was al-
lowed to warm to room temperature and left at that
temperature for 18 h. The reaction mixture was ex-
tracted with cold water, washed with cold dilute HCl
NaBH CN with the organomercuric bromide 4 was not
3
particularly successful but a significant improvement
was observed with the organomercuric acetate interme-
diate 3. Initial oxidation reactions at room temperature
gave modest yields of 18%, which improved to 27% at
10 °C and 45% at 5 °C. Benzoylation of 3 gave the de-
sired alkoxyamine 1.
(0.2 M), followed by cold dilute NaOH (0.2 M) and fi-
nally brine. The organic layer was dried over sodium
sulfate, filtered, evaporated to dryness under vacuum
and purified by flash chromatography (eluent: 20% ethyl
acetate in hexane). The product was a colourless oil that
12
3
. General procedure for the synthesis of 3
1
crystallized on standing, mp 37–39 °C. H NMR
Mercuric acetate (9.8 g, 31 mmol) was dissolved in water
100 mL) in a 250 mL beaker and t-BuA (4.8 mL,
3 mmol) added to the stirred solution at room tem-
3
4
(
)20 °C): d 8.06 (m, J ¼ 8:4Hz, J ¼ 1:3 Hz, 2H17);
(
3
3
4
7
.60 (m, J ¼ 7:4Hz, J ¼ 1:3 Hz, 1H19); 7.46 (m,
3
J
av ¼ 7:8 Hz, 2H18); 4.72, 4.56, 4.53 (ABX spin system,
perature. Stirring was continued for 7 h, after which the
solution was evaporated to dryness to yield a colourless,
2
3
3
J ¼ À11:0 Hz, J ¼ 6:8 Hz, J ¼ 4:5 Hz, 1H1, 1H2,
1
1
3
(
(
(
H1); 1.56 (m, 1H8); 1.46 (m, 2H7, 2H9); 1.41 (s, 9H5);
.32 (m, 1H8); 1.23, 1.18, 1.15, 1.12 (4s, 3H12, 3H14,
1
2
viscous oil. H NMR (20 °C): d 4.13 (dd, J ¼ 11:6 Hz,
3
2
3
J ¼ 3:5 Hz,
J
HgH ¼ 290 Hz,
1H1);
3.82
(dd,
13
H13, 3H11). C NMR ()20 °C): d 170.23 (C3); 166.06
C15); 133.19 (C19); 129.62 (C17); 129.33 (C16); 128.34
C18); 82.76 (C2); 81.67 (C4); 63.90 (C1); 59.99, 59.90
C10, C6); 39.95, 39.92 (C9, C7); 33.51, 33.15, 20.04,
3
3
J ¼ 11:6 Hz, J ¼ 5:8 Hz, JHgH ¼ 123 Hz, 1H1); 3.60
3
3
(
vbr s, OH); 3.44 (dd, J ¼ 5:8 Hz, J ¼ 3:5 Hz,
2
0.04(C12, C13, C11, C1 4) ; 27.81 (C5); 16.91 (C8). EI
þ
1
8
17
7
8
þ
7
O
O
O
MS: M not observed; M ) OtBu, m=z 332; major
1
2
1
6
þ
6
9
1
19
fragment ions: 193, 156, 105, 249. HR MS: M ) OtBu,
1
1
HO
O
15
6
2
N
10
m=z 332.1863; calculated for C H NO : 332.1862.
19
26
4
HgO
1
4
2
1
3
O
O
3
14
3
O
References and notes
4
O
5
1. (a) Goto, A.; Fukuda, T. Macromolecules 1999, 32, 618;
b) Marque, S.; Mercier, C. L.; Tordo, P.; Fischer, H.
5
(