Palladium-catalyzed SN1 reactions of secondary benzylic alcohols: Etherification, amination, and thioetherification

Article abstract of DOI:10.1002/ejoc.200390185

The reaction of various secondary benzylic alcohols in the presence of Pd^II catalysts provides ethers in good to high yields, Unsymmetric ethers could also be obtained with good selectivity by coupling two different alcohols. Direct amination is observed with electron-deficient anilines, and thioethers are prepared conveniently in high yields by the direct action of thiols on sec-phenylethyl alcohol. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.

Full text of DOI:10.1002/ejoc.200390185

FULL PAPER
Palladium-Catalyzed SN1 Reactions of Secondary Benzylic Alcohols:
Etherification, Amination, and Thioetherification
Kimberly J. Miller[a] and Mahdi M. Abu-Omar*[a]
Keywords: Homogeneous catalysis / Palladium / Phosphane ligands / Alcohols / Nucleophilic substitution
The reaction of various secondary benzylic alcohols in the
presence of PdII catalysts provides ethers in good to high
yields. Unsymmetric ethers could also be obtained with good
selectivity by coupling two different alcohols. Direct amin-
ation is observed with electron-deficient anilines, and thio-
ethers are prepared conveniently in high yields by the direct
action of thiols on sec-phenylethyl alcohol.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2003)
Catalytic chemistry plays a central role in the develop- (Table 1) with sec-phenylethyl alcohol as substrate. The ac-
ment of efficient, selective, and environmentally friendly or- tive form of the catalyst was generated in situ by the action
ganic transformations. A wide variety of synthetic methods of two equivalents of silver triflate (AgOTf). As evidenced
have been noted for the preparation of ethers from alcohols, by the result in entry 3 of Table 1, an available coordination
but not without limitations. The most widely used William- site is a prerequisite for catalysis. The reaction proceeds in
son ether synthesis requires the conversion of alcohols to a number of solvents: toluene, dichloromethane, 1,2-dichlo-
halides or tosylates, resulting in excessive salt waste by- roethane, 1,4-dioxane and THF; but due to the high solu-
product.[1] Alternative routes include, but are not limited to, bility of the catalysts in nitromethane, it is the solvent of
acid catalysis,[2] UV irradiation[3] and refluxing in dimethyl choice. Other organic solvents such as toluene require the
sulfoxide.[4] However, the harsh conditions under which use of the more exotic and expensive AgBArF {BArF
ϭ
4
4
these processes are conducted and the mixture of products [(3,5-(CF3)2C6H3)4B]Ϫ} to give soluble Pd catalysts.[7] Con-
that often result limit their utility. Worthy of special men- trol reactions employing the silver salts AgOTf or AgBArF
4
tion is the work of Boyer and co-workers, in which BiBr3 is alone afford no ether formation under the employed reac-
employed in the benzylation of aliphatic alcohols.[5] Even tion conditions (entry 9). The efficiency of a given Pd cata-
though transition metal catalysts seem ideal for the selective lyst is dependent on the steric bulk of the ligand (entries
etherification of alcohols, only a small number of metals 1 & 2, and 6 & 7). It is interesting to note that nitrogen-
have been investigated.[6] In this paper, we report on a facile and phosphorus-based ligands exhibit similar reactivities.
and direct method for preparing symmetric and unsym- However, catalysts with nitrogen-based ligands such as
metric ethers under mild conditions employing cationic pal- Phen were less stable under catalytic conditions than their
ladium phosphane catalysts. Moreover, we have extended phosphorus counterparts, giving palladium mirrors. For
the catalytic reaction to include direct amination of al- this reason, the diop ligand was employed in defining the
cohols and preparation of thioethers form thiols and al- scope of these catalytic systems with different substrates.
cohols. The advantages of the Pd-catalysts described herein
While chiral ligands were employed with most of the
[6c]
over the use of FeCl3
are high selectivity for secondary studied catalysts (Table 1), mixtures of diastereomers and
benzylic alcohols, low catalyst loading, lack of elimination enantiomers were obtained consistently. This suggested the
side products, and versatility in amination and thioether- involvement of a carbocation intermediate. Supporting evi-
ification reactions.
dence for such a mechanism was provided by 1,2,3,4-tetra-
hydro-1-naphthol, which gave 1,2-dihydro-1-naphthalene
(E1 product), and the ether in a 1:1 ratio. This was the
only substrate, however, that gave detectable E1 product.
Furthermore, when the enantiomerically pure (S)-(Ϫ)-sec-
phenylethyl alcohol was employed, we recovered a dia-
stereomeric and racemic mixture of bis-sec-phenylethyl
ether (1a). To elucidate the rate determining step (RDS) in
the catalytic reaction, we determined the kinetic depen-
dence of the alcohol (benzhydrol) at a given catalyst —
[{(R,R)-diop}PdCl2] ϩ 2AgOTf — concentration (Fig-
ure 1). The reaction is first order in concentration of al-
Results and Discussion
Several palladium() complexes containing nitrogen- and
phosphorus-based bidentate ligands were investigated
[a]
Department of Chemistry and Biochemistry, University of
California,
607 Charles E. Young Drive East, Los Angeles, CA 90095-
1569, USA
Fax: (internat.) ϩ1-310/206-9130
E-mail: mao@chem.ucla.edu
1294
 2003 WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim 1434Ϫ193X/03/0407Ϫ1294 $ 20.00ϩ.50/0 Eur. J. Org. Chem. 2003, 1294Ϫ1299

Palladium-Catalyzed SN1 Reactions of Secondary Benzylic Alcohols
FULL PAPER
Table 1. [PdIICl2(L-L)] catalysts for the etherfication of sec-phenyl-
ethyl alcohol[a]
Entry
Catalyst[b]
Yield (%)
1
2
3
4
5
6
7
8
9
[{(R,R)-Me-duphos}PdCl2] ϩ 2AgOTf
[{(R,R)-diop}PdCl2] ϩ 2AgOTf
[{(R,R)-diop}PdCl2]
9
83
0
49
80
80
66
75
0
[(dppe)PdCl2] ϩ 2AgOTf
[{(S,S)-chiraphos}PdCl2 ϩ 2AgOTf
[{(S)-iPr)pyox}PdCl2] ϩ 2AgOTf
[{(S)-iPr)Phpyox}PdCl2] ϩ 2AgOTf
[(phen)PdCl2] ϩ 2AgOTf
Scheme 1. Proposed catalytic sequence of reactions
AgOTf or AgBArF
4
[a]
Conditions: [sec-phenylethyl alcohol] ϭ 1.0 , [Pd] ϭ 0.020 ,
and [AgOTf] ϭ 0.040  in CH3NO2 (VT ϭ 0.80 mL) at 50 °C for
[b]
Given its high reactivity, ease of preparation, and high
stability, the [{(R,R)-diop}PdCl2]/AgOTf catalyst was used
in exploring symmetric ether formation from various al-
cohols. We discovered that only secondary benzylic alcohols
are suitable and selective for ethers (Table 2). The ether
24 hours.
Me-duphos ϭ (Ϫ)-1,2-bis[(2R,5R)-2,5-dimethylphos-
pholano]benzene; diop ϭ (4R,5R)-(ϩ)-O-Isopropylidene-2,3-di-
hydroxy-1,4-bis(diphenylphosphanyl)butane; dppe 1,2-bis(di-
ϭ
phenylphosphanyl)ethane; chiraphos ϭ (2S,3S)-(Ϫ)-bis(diphenyl-
phosphanyl)butane; pyox ϭ (S)-2-[4,5-dihydro-4-(1-methylethyl)-
oxazol-2-yl]pyridine;
Phpyox
ϭ
(S)-2-[4,5-dihydro-4-(1-
methylethyl)oxazol-2-yl]-6-phenylpyridine; phen
anthroline.
ϭ
(1,10)-phen- yields varied from moderate (35%) to excellent (99%) de-
pending on the nucleophilicity of the alcohol. The ether
products are easily purified and isolated by flash chroma-
tography. For example, ethers 3 and 1a were isolated in 75%
cohol and not second order; hence, carbocation formation and 70% yield, respectively. Even though reactions were al-
is the RDS, Scheme 1. The racemization of the ether prod- lowed to stand for one day, most reactions were complete
uct is due to the fact that the etherification is reversible within 3Ϫ4 hours. The success of secondary benzylic al-
(vide infra per thiol reaction).
cohols is related to the stability of their respective carbo-
Figure 1. Plot of ln[ROH] (᭜) and 1/[ROH] (᭪) versus time for the etherification of benzhydrol by [{(R,R)-diop}PdCl2]/2AgOTf;
conditions: [ROH] ϭ 0.50 , [{(R,R)-diop}PdCl2] ϭ 0.01 , and [AgOTf] ϭ 0.02  in CH3NO2 at 50 °C
Eur. J. Org. Chem. 2003, 1294Ϫ1299
1295

K. J. Miller, M. M. Abu-Omar
FULL PAPER
cation. As for tertiary benzyl alcohols such as 2-phenyl-2-
butanol, a mixture of products was obtained with no evi-
dence of ether formation.
Table 3. Formation of unsymmetric ethers by coupling sec-phenyl-
ethyl alcohol and benzylic or alkyl alcohols[a]
Table 2. Formation of symmetric ethers from secondary benzylic
alcohols catalyzed by [{(R,R)-diop}PdCl2]/2AgOTf
[a]
Conditions: sec-phenylethyl alcohol ϭ 0.50 mmol, substrate ϭ
0.50 mmol, (R,R-(Ϫ)-(diop)PdCl2 ϭ 0.020 mmol, and AgOTf ϭ
0.040 mmol in nitromethane (VT ϭ 0.80 mL) at 50 °C for 24 hours.
[a]
[b]
[c]
Conditions: alcohol ϭ 1.0 mmol, (R,R-(Ϫ)-(diop)PdCl2
ϭ
ϭ
Based on sec-phenylethyl alcohol concentration. Determined
by GC/MS and 1H NMR spectroscopy; the remaining balance is
the symmetric ether bis(sec-phenylethyl) ether. [d] Products were 1:1
mixtures of dl enantiomers and meso compounds.
0.020 mmol, and AgOTf ϭ 0.040 mmol in nitromethane (VT 1
[b]
0.80 mL) at 50 °C for 24 hours. Determined by GC/MS and H
NMR spectroscopy. [c] All products were 1:1 mixtures of dl enanti-
omers and meso compounds. [d] 75% isolated yield. 70% isolated
[e]
yield.
Alkyl phenylethyl ethers such as phenylethyl ethyl ether
and phenylethyl isopropyl ether are widely used in the per-
fume industry and are important oxygenates in reformu-
lated gasoline.[8] Hence, we took advantage of our system’s
selectivity for secondary benzyl alcohols and explored its
utility in the preparation of unsymmetrical aromatic ethers
with a variety of primary and secondary alcohols, including
diols (Table 3). Various benzylic and alkyl alcohols were
Table 4. Formation of secondary amines from the direct amination
of sec-phenylethyl alcohol with electron-deficient anilines[a]
used with phenylethyl alcohol to provide excellent to mod- Entry Substrate
erate yields of the unsymmetric ether. In every case, the con-
Product
Conv.
(%)[b]
Yield
(%)[c]
version of sec-phenylethyl alcohol to ether products ex-
1
2
3
R1 ϭ R2 ϭ R3 ϭ F
12
13
14
95
86
94
64
39
45
ceeded 90%. The only side product was the symmetric
bis(sec-phenylethyl) ether; however, in most cases, the un-
symmetric ether was the major product. In case of entry 5,
since both substrates are secondary benzylic alcohols, sym-
metric ethers from both alcohols account for the balance in
the yield.
R2 ϭ H, R1 ϭ R3ϭ F
R2 ϭ H, R1 ϭ R3 ϭ Cl
[a]
Conditions: sec-phenylethyl alcohol ϭ 0.50 mmol, substrate ϭ
0.50 mmol, (R,R)-(Ϫ)-(diop)PdCl2 ϭ 0.020 mmol, and AgOTf ϭ
0.040 mmol in nitromethane (VT ϭ 0.80 mL) at 50 °C for 24 hours.
[b]
[c]
Based on sec-phenylethyl alcohol concentration. Determined
Amines have found uses as antioxidants in fuel oils, rub-
by GC/MS; the remaining balance is the symmetric ether bis(sec-
ber stabilizers, medicinal drugs, detergents, and herbi- phenylethyl) ether.
1296
Eur. J. Org. Chem. 2003, 1294Ϫ1299

Palladium-Catalyzed SN1 Reactions of Secondary Benzylic Alcohols
FULL PAPER
cides.[9] Generally, alcohol aminations require the conver- lated in 98% yield (entry 3) to illustrate the high efficiency
sion of the alcohol to a halide. The method described herein of this method on a preparative scale.
is a direct one that employs anilines and sec-phenylethyl
An interesting observation was the conversion of any
alcohol. Since palladium() has a high affinity for amine bis(sec-phenylethyl) ether formed during the reaction to the
ligands,[10] anilines are problematic in that they bind irrever- thioether product. In fact, when bis-sec-phenylethyl ether
sibly to our PdII complexes, inhibiting catalysis. Hence, only (1a) and 1-butanethiol in a 1:2 ratio, respectively, were com-
electron-deficient anilines reacted with sec-phenylethyl al- bined in the presence of [{(R,R)-diop}PdCl2]/2AgOTf, after
cohol to yield the secondary amine in moderate to good two hours (sec-phenylethyl) n-butyl thioether 17 was ob-
yields (Table 4). Another limitation of this method is that served as the exclusive product in solution. Control reac-
the symmetric ether from sec-phenylethyl alcohol is always tions without catalyst showed no reaction over days under
a side product. A study of 2,6-diisopropylaniline with the the same conditions. Hence, we propose that the ether re-
hope of blocking coordination to Pd was not successful as acts with palladium to form an alkoxide complex of PdII
only starting materials were recovered.
along with a carbocation intermediate. The latter is cap-
Bis(diphenylphosphanyl)methane complexes of plati- tured by the thiol, yielding the thioether and a proton. The
num() have been shown to catalyze the formation of thioe- palladium alkoxide complex is protonated to regenerate the
thers from thiols and alkyl halides or geminal dihalides.[11] starting palladium catalyst and sec-phenylethyl alcohol.
The procedure described here is direct and more con-
venient. The reaction of sec-phenylethyl alcohol with aro-
Conclusion
matic, benzylic, and alkyl thiols proceeds smoothly to give
exclusively the thioether product (Table 5). One exception is
the reaction with 2-mercaptoethanol (entry 5) in which both
the ether and thioether are formed. Thioether 17 was iso-
In summary, we have developed an efficient PdII catalytic
system for the direct preparation of symmetric and unsym-
metric aromatic ethers, for the amination of secondary
benzylic alcohols, and for the direct formation of thioethers.
Table 5. Formation of thioethers from the direct reaction of sec-
phenylethyl alcohol with thiols[a]
Experimental Section
General Remarks: Solvents and reagents for all reactions were used
as received from commercial suppliers unless noted otherwise. (S)-
2-[4,5-dihydro-4-(1-methylethyl)oxazol-2-yl]-6-phenylpyridine,[12]
(S)-2-[4,5-dihydro-4-(1-methylethyl)oxazol-2-yl]-pyridine[13,14] and
all palladium dichloride complexes[15] were prepared according to
literature methods. GC/MS analyses were performed on an Agilent
6890 GC equipped with a medium polarity bonded-phase fused
silica capillary column (30 m ϫ 0.25 mm, DB5, J & W Assoc. Fol-
som, Ca., injector port and GCMS transfer line at 250 °C, oven 50
°C for 3 min following injection then increased linearly at 15 °C/
min to a plateau of 300 °C) the end of which was inserted directly
into the EI source (70 eV, 180 °C) of a TOF mass spectrometer
(Micromass GCT). Chromatographic purification was performed
˚
using columns packed with EM Silica Gel 60 A (200Ϫ400 mesh)
that had been dried overnight at 100 °C. CH3NO2 was distilled
from CaH2 immediately before use. NMR spectra were obtained
with a Bruker 400 or 500 MHz spectrometer and referenced to
TMS; the solvent is specified for each of the compounds.
A Typical Catalytic Procedure: In a vial equipped with a stir bar,
[{(R,R)-diop}PdCl2] (0.0108 g, 0.016 mmol) and AgOTf (0.0081 g,
0.032 mmol) were dissolved in 0.7 mL of dry CH3NO2. The solu-
tion was allowed to stir at room temperature for a couple of mi-
nutes to allow for the formation of the active catalyst as indicated
by the color change from a pale to bright yellow. (Ϯ)-sec-Phenyle-
thyl alcohol (98 µL, 0.8 mmol) was then added via a syringe. The
solution (VT ϭ 0.8 mL) was capped and placed in a 50 °C sand
bath for 24 hours. Afterwards, the solvent was removed under vac-
uum. The organic residue was purified by flash chromatography on
silica gel (1:1, hexanes and diethyl ether) and characterized by GC/
[a]
Conditions: sec-phenylethyl alcohol ϭ 0.50 mmol, substrate ϭ
0.50 mmol, (R,R)-(Ϫ)-(diop)PdCl2 ϭ 0.02 mmol, and AgOTf ϭ
0.04 mmol in nitromethane (VT ϭ 0.80 mL) at 50 °C for 24 hours.
[b]
[c]
1
MS, H and 13C NMR spectroscopy.
Based on sec-phenylethyl alcohol concentration. Determined
by GC/MS and 1H NMR spectroscopy.
98% isolated yield.
[d]
Bis(α-methyl-2-naphthalene)methyl Ether (2):[16] (0.32 g, 99%). 1H
NMR (CDCl3): δ ϭ 7.87Ϫ7.80 (m, 16 H), 7.51Ϫ7.41 (m, 12 H),
[e]
[f]
Starting material was a racemic mixtures. Products were 1:1
mixtures of dl enantiomers and meso compounds.
Eur. J. Org. Chem. 2003, 1294Ϫ1299
1297

K. J. Miller, M. M. Abu-Omar
FULL PAPER
4.74 (q, 2 H)*, 4.45 (q, 2 H)*, 1.58Ϫ1.51 (2m, 12 H)* ppm. 13C
[M Ϫ CH3]ϩ; calcd.: 234.38 (C16H26O), 219.35 (C15H23O) Da. *
NMR (CDCl3): δ ϭ 141.54, (141.38), 133.20, (133.13), 132.95, diastereomeric pairs.
(132.74), 128.33, (127.94), 127.73(2), 127.63, (127.50), 126.00(2),
1
Benzyl (؎)-sec-Phenylethyl Ether (8):[18] (0.072 g, 68%). H NMR
(CDCl3): δ ϭ 7.40Ϫ7.26 (m, 10 H), 4.54 (q, 1 H), 4.49 (d, 1 H),
4.36 (d, 1 H), 1.51 (d, 3 H) ppm. 13C NMR (CDCl3): δ ϭ 143.50,
138.41, 128.29, 128.14, 127.49, 127.29, 126.13, 125.08, 70.08,
24.01 ppm. GC/MS: tR ϭ 10.77 min, obs. MS: m/z ϭ Mϩ· (not
observed), 197.11 [M Ϫ CH3]ϩ; calcd.: 212.29 (C15H16O), 197.26
(C14H13O) Da.
125.65(2), 125.12, (124.77), 124.20(2), 74.70, (74.50), 24.45, (22.78)
ppm. GC/MS: tR ϭ 14.85 & 15.10 min (dl and meso), obs. MS:
m/z ϭ Mϩ· (not observed), 172.10 [M Ϫ C12H10]ϩ, 154.07 [M Ϫ
C12H12O]ϩ; calcd.: 326.44 (C24H22O), 172.23 (C12H12O), 154.21
(C12H10) Da. * diastereomeric pairs.
1
Bis(diphenyl)methyl Ether (3):[6a] (0.35 g, 99%). H NMR (CDCl3):
δ ϭ 7.38Ϫ7.25 (m, 20 H), 5.40 (s, 2 H) ppm. 13C NMR (CDCl3):
1-(2-Naphthyl)ethyl (؎)-sec-Phenylethyl Ether (9): (0.070 g, 51%).
1H NMR (CDCl3): δ ϭ 7.89Ϫ7.26 (4m, 12 H), 4.76 (q, 1 H), 4.55
(q, 1 H), 1.49 (d, 3 H), 1.42 (d, 3 H) ppm. 13C NMR (CDCl3): δ ϭ
141.54, (141.40), 133.23, (132.97), 128.42, 128.39, 128.18, 127.98,
127.80, 127.76, 127.60, 127.39, 127.34, 127.11, 126.25, 126.17,
126.08, 126.04, 126.02, 125.72, 125.69, 125.67, 125.32, 125.18,
125.15, 124.49, 124.25, 74.61, (74.55), 24.52, (24.50), 22.81,
22.78 ppm. GC/MS: tR ϭ 14.20 min, obs. MS: m/z ϭ Mϩ· (not
observed), 154.07 [M Ϫ C12H12O]ϩ, 105.07 [M Ϫ C16H13O]ϩ;
calcd.: 276.38 (C20H20O), 154.21 (C12H10), 105.16 (C8H9) Da.
δ ϭ 142.11, 128.30, 127.35, 127.12, 79.90 ppm. GC/MS: tR
ϭ
14.80 min, obs. MS: m/z ϭ Mϩ· (not observed), 183.09 [M Ϫ
C13H11]ϩ, 167.08 [M Ϫ C13H11O]; calcd.: 350.46 (C26H22O), 183.23
(C13H11O), 167.23 (C13H11) Da.
Bis-1-(4-methylphenyl)ethyl Ether (1b): (0.25 g, 99%). 1H NMR
(CDCl3): δ ϭ 7.26Ϫ7.16 (m, 8 H), 7.12 (m, 8 H), 4.51 (q, 2 H)*,
4.24 (q, 2 H)*, 2.36 (s, 6 H)*, 2.33 (s, 6 H)*, 1.45 (d, 6 H)*, 1.38
(d, 6 H)* ppm. 13C NMR (CDCl3): δ ϭ 141.08, (141.24), 136.90,
(136.63), 129.09, (128.85), 126.21, (126.11), 74.16, (73.83), 24.63,
(22.79), 21.07, (21.01) ppm. GC/MS: tR ϭ 10.82 min, obs. MS:
m/z ϭ Mϩ· (not observed), 239.17 [M Ϫ CH3]ϩ; calcd.: 254.37
(C18H22O), 239.34 (C17H19O) Da. * diastereomeric pairs.
Isopropyl (؎)-sec-Phenylethyl Ether (10):[19] (0.039 g, 48%). 1H
NMR (CDCl3): δ ϭ 7.37Ϫ7.26 (m, 5 H), 4.54 (q, 1 H), 3.49 (sept,
1 H), 1.41 (d, 3 H), 1.16 (d, 3 H), 1.10 (d, 3 H) ppm. 13C NMR
(CDCl3): δ ϭ 144.81, 128.27, 127.12, 126.07, 74.55, 68.44, 24.74,
23.25, 21.30 ppm. GC/MS: tR ϭ 5.90 min, obs. MS: m/z ϭ Mϩ·
(not observed), 149.10 [M Ϫ CH3]ϩ; calcd.: 164.25 (C11H16O),
149.21 (C10H13O) Da.
Bis-1-[4-(trifluoromethyl)phenyl]ethyl Ether (1c): (0.13 g, 35%). 1H
NMR (CDCl3): δ ϭ 7.62 (d, 4 H)*, (d, 4 H)*, 7.46 (d, 4 H)*, 7.40
(d, 4 H)*, 4.56 (q, 2 H)*, 4.28 (q, 2 H)*, 1.40 (d, 12 H)* ppm. 13C
NMR (CDCl3): δ ϭ 147.92(2), 126.46, 126.35, 125.56(2), 125.27(2),
74.65, 74.62, 24.50, 23.14 ppm. GC/MS: tR ϭ 6.38 min, obs. MS:
m/z ϭ Mϩ· (not observed), 189.06 [M Ϫ C9H8F3]ϩ, 173.05 [M Ϫ
C9H8OF3]ϩ; calcd.: 362.31 (C18H16F6O), 189.16 (C9H8OF3), 173.16
(C9H8F3) Da. * diastereomeric pairs.
1,2-Diphenyl-2-(1-phenylethoxy)-1-ethanone (11): (0.057 g, 36%). 1H
NMR (CDCl3): δ ϭ 7.80 (d, 2 H), 7.40Ϫ7.26 (m, 13 H), 5.53 &
5.47 (2s, 1 H)*, 4.59 & 4.48 (2q, 1 H)*, 1.52Ϫ1.50 (2d, 3 H)* ppm.
13C NMR (CDCl3): δ ϭ 198.65, 142.67, (142.41), 134.84, 133.12,
132.87, 129.82, 129.14, (129.04), 128.72, (128.67), 128.54(2), 128.39,
128.18, 127.85(2), 127.34, 127.05, 126.70, 126.41, 125.31, 82.35,
(81.41), 24.14, (23.83) ppm. GC/MS: tR ϭ 15.50 min, obs. MS:
Bis(1,2,3,4-tetrahydro-1-napthyl) Ether (4):[6e] (0.15 g, 55%). 1H
NMR (CDCl3): δ ϭ 7.17Ϫ7.14 (m, 12 H), 7.12Ϫ7.11 (m, 4 H),
3.73 (br. t, 4 H), 2.21 (q, 4 H)*, 2.15 (q, 4 H)*, 1.98 (m, 8 H)*,
1.84 (q, 4 H)*, 1.77 (q, 4 H)* ppm. 13C NMR (CDCl3): δ ϭ 145.56,
(137.85), 137.63, (134.05), 129.18, (128.99), 127.09, (126.24),
125.90, (125.56), 125.51, (125.06), 47.23, 29.75, 28.49, (28.47),
(21.37) ppm. GC/MS: tR ϭ 13.50 min, obs. MS: m/z ϭ Mϩ· (not
observed), 260.16 [M Ϫ OH2]ϩ; calcd.: 278.39 (C20H22O), 260.38
(C20H20) Da. * diastereomeric pairs.
m/z ϭ Mϩ· (not observed), 211.13 [Mϩ· Ϫ C8H9], 105.07 [Mϩ·
Ϫ
C14H11O2]; calcd.: 316.40 (C22H20O2), 211.24 (C14H11O2), 105.16
(C8H9) Da. *diastereomeric pairs
N-(؎)-α-methyl-benzyl-N-pentafluorobenzylamine (12): (0.092 g,
1
64%). H NMR (CDCl3): δ ϭ 7.42Ϫ7.27 (m, 5 H), 4.96 (q, 1 H),
3.74 (br. s, 1 H), 1.61 (d, 3 H) ppm. 13F NMR (CDCl3): δ ϭ Ϫ158.3
(d, 2 F), Ϫ164.8 (t, 2 F), Ϫ170.9 (t, 1 F) ppm. GC/MS: tR
9.92 min, obs. MS: m/z
(C14H10F5N) Da.
ϭ
(1-Hydroxy)ethyl (؎)-sec-Phenylethyl Ether (5):[17] (0.078 g, 95%).
1H NMR (CDCl3): δ ϭ 7.34Ϫ7.25 (m, 5 H), 4.45 (q, 1 H), 3.67
(m, 2 H), 3.41 (m, 2 H), 3.28 (br. s, 1 H), 1.42 (d, 3 H) ppm. 13C
NMR (CDCl3): δ ϭ 143.32, 128.45, 127.30, 126.22, 78.41, 69.64,
61.87, 24.00 ppm. GC/MS: tR ϭ 7.87 min, obs. MS: m/z ϭ 166.11
(Mϩ·); calcd.: 166.22 (C10H14O2) Da.
ϭ
287.08 [Mϩ·]; calcd.: 287.23
N-(؎)-α-methylbenzyl-N-2,4,6-trifluorobenzylamine (13): (0.049 g,
1
39%). H NMR (CDCl3): δ ϭ 7.37Ϫ7.26 (2m, 5 H), 6.55 (t, 2 H),
4.71 (q, 1 H), 3.74 (br. s, 1 H), 1.55 (d, 3 H) ppm. 19F NMR
(CDCl3): δ ϭ Ϫ120.59 (s, 2 F), Ϫ124.15 (s, 1 F) ppm. GC/MS:
tR ϭ 9.85 min, obs. MS: m/z ϭ 251.11 [Mϩ·]; calcd.: 251.25
(C14H12N F3) Da.
Ethyl (؎)-sec-Phenylethyl Ether (6):[6a] (0.056 g, 74%). 1H NMR
(CDCl3): δ ϭ 7.35Ϫ7.25 (m, 5 H), 4.41 (q, 1 H), 3.35 (q, 2 H), 1.45
(d, 3 H), 1.17 (t, 3 H) ppm. 13C NMR (CDCl3): δ ϭ 143.93, 128.07,
126.99, 125.79, 77.42, 63.58, 24.32, 15.09 ppm. GC/MS: tR
ϭ
N-(؎)-α-methylbenzyl-N-2,4,6-trichlorobenzylamine (14): (0.068 g,
45%). 1H NMR (CDCl3): δ ϭ 7.38Ϫ7.20 (2 m, 5 H), 7.19 (s, 2 H),
5.57 min, obs. MS: m/z ϭ Mϩ· (not observed), 135.08 [M Ϫ CH3]ϩ;
calcd.: 150.22 (C10H14O), 135.19 (C9H11O) Da.
5.02 (q, 1 H), 4.16 (br. s, 1 H), 1.58 (d, 3 H)ppm. GC/MS: tR
ϭ
13.65 min, obs. MS: m/z ϭ 299.09 [Mϩ·35Cl3], 301.09 [Mϩ·35Cl2,
37Cl], 303.09 [Mϩ·35Cl, 37Cl2], & 305.9 [Mϩ·37Cl3]; calcd.: 299
(C14H12N35Cl3), 301 (C14H12N35Cl2 37Cl), 303 (C14H12N35Cl37Cl2),
305 (C14H12N37Cl3) Da.
1-Methylheptyl (؎)-sec-Phenylethyl Ether (7):[5b] (0.086 g, 73%). 1H
NMR (CDCl3): δ ϭ 7.37Ϫ7.25 (m, 5 H), 4.53 (q, 1 H)*, 3.38 &
3.28 (2sextet, 1 H)*, 1.42 & 1.41 (2d, 3 H)*, 1.29 (m, 10 H), 1.12 &
1.04 (2d. 3 H)*, 0.88 (t, 3 H) ppm. 13C NMR (CDCl3): δ ϭ 145.04,
(144.51), 128.19, (128.15), 127.19, (127.06), 126.41, (126.14), 75.38,
(73.10), 71.83, (68.20), 39.28, 37.50, 36.02, 31.79(2), 29.48, 29.27,
29.20, 25.68, 25.60, 25.25, 24.68, 24.33, 22.57, 19.23, 14.04 ppm.
Phenyl (؎)-sec-Phenylethyl Thioether (15):[20] (0.11 g, 99%). 1H
NMR (CDCl3): δ ϭ 7.30Ϫ7.20 (m, 10 H), 4.35 (q, 1 H), 1.63 (d, 3
H) ppm. 13C NMR (CDCl3): δ ϭ 143.12, 135.04, 132.33, 128.61,
GC/MS: tR ϭ 5.90 min, obs. MS: m/z ϭ Mϩ· (not observed), 219.19 128.31, 127.19, 127.06, 127.03, 47.86, 22.24 ppm. GC/MS: tR
ϭ
1298
Eur. J. Org. Chem. 2003, 1294Ϫ1299

Palladium-Catalyzed SN1 Reactions of Secondary Benzylic Alcohols
FULL PAPER
10.45. min, obs. MS: m/z
(C14H14S) Da.
ϭ
214.11 [Mϩ·]; calcd.: 214.33
0078299). We are grateful to Professor Kym Faull for the use of
GC/MS.
Benzyl (؎)-sec-Phenylethyl Thioether (16):[21] (0.11 g, 99%). 1H
NMR (CDCl3): δ ϭ 7.40Ϫ7.27 (m, 10 H), 3.88 (q, 1 H), 3.60 (d, 1
H), 3.50 (d, 1 H), 1.60 (d, 3 H) ppm. 13C NMR (CDCl3): δ ϭ
143.70, 138.33, 128.80, 128.59, 128.42, 128.32, 127.94, 127.37,
127.00, 126.95, 126.76, 43.47, 35.63, 28.88, 22.46 ppm. GC/MS:
tR ϭ 12.13 min, obs. MS: m/z ϭ 228.10 (Mϩ·), calcd.: 228.35
(C15H16S) Da.
[1]
J. March, Advanced Organic Chemistry, John Wiley & Sons:
New York, 1992, 4th ed, pp. 386Ϫ387.
D. Braun, K. G. Keppler, Monasch Chem. 1963, 94,
1250Ϫ1261.
[2]
[3]
R. E. Balsells, A. R. Frasca, Tetrahedron 1982, 38, 2525Ϫ2538.
[4] [4a]
V. J. Traynelis, W. L. Hergenrother, H. T. Hanson, J. A.
[4b]
Valicenti, J. Org. Chem. 1964, 29, 123Ϫ129.
J. Emert, M.
Golenberg, G. L. Chiu, A. Valeri, J. Org. Chem. 1977, 42,
n-Butyl (؎)-sec-Phenylethyl Thioether (17):[22] (0.096 g, 99%). 1H
NMR (CDCl3): δ ϭ 7.35Ϫ7.23 (m, 5 H), 3.94 (q, 1 H), 2.36Ϫ2.27
(m, 2 H), 1.57 (d, 3 H), 1.50Ϫ1.46 (m, 2 H), 1.40Ϫ1.32 (m, 2 H),
0.85Ϫ0.83 (t, 3 H) ppm. 13C NMR (CDCl3): δ ϭ 144.20, 128.48,
127.30, 127.00, 44.09, 31.51, 31.02, 22.68, 22.09, 13.71 ppm. GC/
MS: tR ϭ 9.25 min, obs. MS: m/z ϭ 194.13 ([Mϩ·]; calcd.: 194.33
(C12H18S) Da.
2012Ϫ2013.
[5] [5a]
B. Boyer, E. M. Keramane, J. P. Roque, A. A. Pavia, Tetra-
[5b]
hedron Lett. 2000, 41, 2891Ϫ2894.
E. M. Keramane, B.
Boyer, J. P. Roque, Tetrahedron 2001, 57, 1917Ϫ1921.
[6] [6a]
Z. Zhu, J. H. Espenson, J. Org. Chem. 1996, 61, 324Ϫ328.
[6b] S. AitMohand, S. Lunak, J. Muzart, Chem. Ber./Recl. 1997,
[6c]
130, 1655Ϫ1658.
P. Salehi, N. Iranpoor, F. K. Behbahani,
[6d]
Tetrahedron 1998, 54, 943Ϫ948.
G. V. M. Sharma, A. K.
Mahalingam, J. Org. Chem. 1999, 64, 8943Ϫ8944. S. Bou-
quillon, F. Henin, J. Muzart, Organometallics 2000, 19,
G. V. M. Sharma, T. Rajendra-Prasad, A. K.
Mahalingam, Tetrahedron Lett. 2001, 42, 759Ϫ761.
[6e]
sec-Butyl (؎)-sec-Phenylethyl Thioether (18): (0.096 g, 99%). 1H
NMR (CDCl3): δ ϭ 7.37Ϫ7.22 (m, 5 H), 4.02 (2q, 1 H)*, 2.52 &
2.41 (2 sext, 1 H)*, 1.46 & 1.40 (quin, 2 H)*, 1.55 (d, 3 H), 1.24 &
1.11 (2d, 3 H)*, 0.92 & 0.86 (2t, 3 H)* ppm. 13C NMR (CDCl3):
δ ϭ 144.60, (144.57), 128.38(2), [128.36(2)], 127.17(2), [127.51(2)],
126.84, (126.83), 43.08, (42.82), 40.81, (40.80), 29.74, (29.47), 23.16,
(22.94), 21.10, (20.26), 11.26, (10.97) ppm. GC/MS: tR ϭ 8.63 &
8.70 min (dl and meso), obs. MS: m/z ϭ 194.12 (Mϩ·), calcd.:
194.33 (C12H18S) Da. * diastereomeric pairs.
´
[6f]
1434Ϫ1437.
[6g]
A. Ka-
wada, K. Yasuda, A. Hitoshi, T. Harayama, Chem. Pharm.
Bull. 2002, 50, 380Ϫ383.
[7]
[8]
For the synthesis of AgBArF4, see: K. J. Miller, T. T. Kitagawa,
M. M. Abu-Omar, Organometallics 2001, 20, 4403Ϫ4412.
G. D. Yadav, V. V. Bokade, Appl. Catal. A: General 1996,
147, 299Ϫ323.
[9]
A. Baiker, W. Richarz, Tetrahedron Lett. 1977, 18, 1937Ϫ1940.
F. A. Cotton, G. Wilkinson, C. A. Murillo, M. Bochmann,
Advanced Inorganic Chemistry, John Wiley & Sons, Inc: New
York, 1999, pp. 1063Ϫ1064.
P. C. B. Page, S. S. Klair, M. P. Brown, C. S. Smith, S. J. Mag-
inn, S. Mulley, Tetrahedron 1992, 48, 5933Ϫ5940.
J. Cheng, T. J. Deming, Macromolecules 1999, 32, 4745Ϫ4747.
G. Chelucci, S. Medici, A. Saba, Tetrahedron: Asymmetry 1999,
10, 543Ϫ550.
G. Chelucci, M. G. Sanna, S. Gladiali, Tetrahedron 2000, 56,
2889Ϫ2893.
M. Sperlle, G. Consiglio, J. Am. Chem. Soc. 1995, 117,
12130Ϫ12136.
[10]
(1-Hydroxy)ethyl (؎)-sec-Phenylethyl Thioether (19): (0.039 g, 43%)
1H NMR (CDCl3): δ ϭ 7.37Ϫ7.22 (m, 5 H), 3.98 (q, 1 H),
3.60Ϫ3.51 (m, 2 H), 2.70Ϫ2.66 (m, 2 H), 2.27 (br. s., 1 H), 1.56 (d,
3 H) ppm. 13C NMR (CDCl3): δ ϭ 143.34, 128.12, 126.94, 125.80,
60.36, 43.62, 34.24, 24.48 ppm. GC/MS: tR ϭ 9.75 min, obs. MS:
m/z ϭ 182.07 [Mϩ·], 137.03 [M Ϫ C2H5O]ϩ, & 105.06 [M Ϫ
C2H5OS]ϩ; calcd.: 182.28 (C10H14OS), 137.22 (C8H9S), & 105.16
(C8H9) Da.
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
1-Mercaptoethyl (؎)-sec-Phenylethyl Ether (20): (0.031 g, 34%). 1H
NMR (CDCl3): δ ϭ 7.33Ϫ7.25 (m, 5 H), 4.41 (q, 1 H), 3.42 (t, 2
H), 3.33 (t, 2 H), 1.52 (t, 1 H), 1.43 (d, 3 H) ppm. 13C NMR
(CDCl3): δ ϭ 143.34, 128.12, 126.94, 125.80, 77.89, 70.12, 23.85,
22.42 ppm. GC/MS: tR ϭ 14.08 min, obs. MS: m/z ϭ 182.07 [Mϩ·],
121.06 [M Ϫ C2H5S]ϩ, & 105.06 [M Ϫ C2H5OS]ϩ; calcd.: 182.28
(C10H14OS), 121.16 (C8H9O), 105.16 (C8H9) Da.
F. C. De Schryver, K. Demeyer, S. Toppet, Macromolecules
1983, 16, 89Ϫ94.
´
J. F. Gil, D. J. Ramon, M. Yus, Tetrahedron 1993, 49,
9535Ϫ9546.
S. Kim, K. N. Chung, S. Yang, J. Org. Chem. 1987, 52,
3917Ϫ3919.
H. C. Brown, J. T. Kurek, M. Rei, K. L. Thompson, J. Org.
Chem. 1984, 49, 2551Ϫ2557.
N. M. Yoon, J. Choi, J. H. Ahn, J. Org. Chem. 1994, 59,
3490Ϫ3493.
T. Mukaiyama, T. Masui, T. Izawa, Chem. Lett. 1976,
1177Ϫ1180.
Acknowledgments
This work was supported by the US National Science Foundation
(CHE-9874857-CAREER) and the Beckman Foundation. Funds
for the purchase of instruments used in this research were made
possible by NSF equipment grants (CHE-9974928 and CHE-
Y. Kikugawa, Chem. Lett. 1981, 1157Ϫ1158.
Received October 2, 2002
[O02547]
Eur. J. Org. Chem. 2003, 1294Ϫ1299
1299