7
078
G. A. Kraus et al. / Tetrahedron Letters 43 (2002) 7077–7078
between the aldehyde and the methyl group at C-4
confirmed the regiochemical assignment. The regio-
chemistry of 10 was determined by 2D NOESY NMR
accord with the assigned structure. Interestingly, alkyla-
tion of triflates 12 and 13 with 2-bromopropane and
aluminum chloride produced both the expected alkyla-
tion products and the products derived from alkylation
followed by demethylation of the aryl methyl ether.
(
only one aromatic ring proton exhibited an interaction
with the methyl group at C-4).
The results from Table 1 indicate that the triflate is
stable under several reaction conditions. The triflate
group is readily removed by treatment with lithium
The triflate, a more durable electron-withdrawing
group than the pivalate, was next studied. Triflates
1
1–14 were synthesized in excellent yields by treatment
6,7
aluminum hydride. As shown below, treatment with
4
of the phenol with triflic anhydride and pyridine. The
reaction of triflates 11–14 with electrophiles afforded
fewer byproducts. The triflates were compatible with a
wider range of electrophiles. Triflates 11–14 afforded
good yields of products in bromination, acylation and
lithium aluminum hydride produces the known alcohol
1
5 in 100% yield.
OTf
OH
OMe
LAH
THF
5
OMe
electrophilic alkylation reactions. These results are col-
lected in Table 1. The regiochemistry of the aldehydes
was determined by 2D NOESY NMR experiments. The
regiochemistry of the products from the reactions with
the triflate of guaiacol was determined by examining
the NMR splitting pattern of the aromatic ring pro-
OHC
HO
15
The use of aryl triflates to control the regiochemistry of
intermolecular acylation, bromination or alkylation
should have broad application. The ease of triflate
introduction coupled with the well-established
1
13
tons. Each product exhibited H, C NMR, IR, a mass
spectrum, and a high resolution mass spectrum in
8
organometallic chemistry of aryl triflates combine to
OTf
OTf
X
offer many avenues for elaboration.
Me
MeO
12: X = Me
13: X = Br
14: X = H
Acknowledgements
Me
11
We thank Iowa State University for partial support of
this work.
Table 1. Reaction of triflates with electrophiles
References
OTf
OTf
R1
R1
E+
1. Ang, H. H.; Hitotsuyanagi, Y.; Takeya, K. Tetrahedron
Lett. 2000, 41, 6849.
. Ballio, A. Gazz. Chim. Ital. 1949, 79, 924.
. Martin, R. Bull. Soc. Chim. Fr. 1977, 901.
. Runge, M.; Haufe, G. J. Org. Chem. 2000, 65, 8737.
. To a solution of 2-methoxy-4-methyl phenyl triflate (0.247
g, 0.915 mmol) and dichloromethyl methyl ether (0.124
mL, 1.37 mmol) in methylene chloride (2 mL), was added
E
2
3
4
5
R2
R2
+
R1
R2
E
% Yield
41
Me
Me MeOCHCl /TiCl , CH Cl , 0°C–rt,
2
4
2
2
1
2 h
dropwise TiCl (0.281 mL, 2.56 mmol) at 0°C under Ar.
4
OMe Me MeOCHCl /TiCl , CH Cl , 0°C–rt,
96
2
4
2
2
The resulting mixture was stirred overnight to rt. The
reaction was poured into ice water and extracted with
methylene chloride. The organic layer was washed with
NaHCO3 and brine and then dried with MgSO4 and
evaporated in vacuo. The crude material was purified by
silica gel flash chromatography using 5:1 hexanes:ethyl
acetate.
1
2 h
OMe Me Br /HOAc, rt, 12 h
OMe Me CH COCl/AlCl , ClCH CH Cl, rt, 6
100
95
2
3
3
2
2
h
OMe Me iPrBr/AlCl , ClCH CH Cl, rt, 30 h
51a
47
3
2
2
OMe Br
MeOCHCl /TiCl , CH Cl , 0°C–rt,
1
iPrBr/AlCl , ClCH CH Cl, rt, 12 h
MeOCHCl /TiCl , CH Cl , 0°C–rt, 5
2 4 2 2
8 h
OMe Br
42b
99
3
2
2
4-Methoxy-2-methyl-5-trifluoromethanesulfonyloxybenz-
OMe
OMe
H
H
1
2
4
2
2
aldehyde: H NMR (CDCl ) 2.72 (s, 3H), 4.01 (s, 3H),
3
h
13
6
1
1
3
2
.89 (s, 1H), 7.69 (s, 1H), 10.15 (s, 1H). C NMR (CDCl3)
9.3, 56.7, 115.8, 118.8 (q, J=318 Hz), 124.8, 127.5, 137.2,
43.7, 155.4, 189.4. IR (film) 2870, 1709, 1607. MS m/z
00, 298, 165, 109. HRMS m/z for C H F O S: calcd
CH COCl/AlCl , ClCH CH Cl, 0°C,
1
94
3
3
2
2
2 h
10
9
3
5
98.0123, found: 298.0127.
OTf
OTf
OH
6
7
. VanBrocklin, H. F.; Liu, A.; Welch, M. J.; O’Neill, J. P.;
Katzenellenbogen, J. A. Steroids 1994, 59, 34.
. Kurz, L.; Lee, G.; Morgans, D., Jr.; Waldyke, M. J.;
Ward, T. Tetrahedron Lett. 1990, 31, 6321.
OH
a: 34%
b: 56%
Br
8. Ritter, K. Synthesis 1993, 735–762.