Competing Regiochemical Pathways in the Heck Arylation of 1,2-Dihydronaphthalene

Article abstract of DOI:10.1002/1615-4169(200201)344:1<104::AID-ADSC104>3.0.CO;2-V

The Heck reaction of aryl iodides with 1,2-dihydronaphthalene has been examined. Two separate reaction pathways are observed under all the conditions tried. Arylation adjacent to the aromatic ring leads to a subsequent double bond shift such that the product is a 1-aryl-1,2-dihydronaphthalene. The alternative regiochemistry leads to production of the corresponding 3-aryl-1,2-dihydronaphthalene, and labelling studies with specifically deuterated alkenes demonstrate that this is most likely to be the result of a trans Pd-H elimination pathway. The ratio always varies between 75:25 in favour of the 3-aryl product (Jeffery conditions) to 70:30 in favour of the 1-aryl product.

Full text of DOI:10.1002/1615-4169(200201)344:1<104::AID-ADSC104>3.0.CO;2-V

FULL PAPERS
Competing Regiochemical Pathways in the Heck Arylation of 1,2-
Dihydronaphthalene
Kenji Maeda, Edward J. Farrington, Erwan Galardon, Benjamin D. John,
John M. Brown*
Dyson Perrins Laboratory, Department ofChemistry, South Parks Rd., Oxford OX1 3QY, U.K.
Tel. ( ‡ 44)-1865-275642, Fax ( ‡ 44)-1865-275674, e-mail: bjm@herald.ox.ac.uk
Received October 4, 2001; Accepted November 22, 2001
Abstract: The Heck reaction ofaryl iodides with 1,2-
dihydronaphthalene has been examined. Two separate
reaction pathways are observed under all the conditions
tried. Arylation adjacent to the aromatic ring leads to a
subsequent double bond shift such that the product is a 1-
aryl-1,2-dihydronaphthalene. The alternative regiochemis-
try leads to production ofthe corresponding 3-aryl-1,2-
dihydronaphthalene, and labelling studies with specifically
deuterated alkenes demonstrate that this is most likely to be
the result ofa trans Pd-H elimination pathway. The ratio
always varies between 75:25 in favour of the 3-aryl product
(Jeffery conditions) to 70:30 in favour of the 1-aryl product.
Keywords: deuterated alkenes; dihydronaphthalene; trans-
elimination; Heck reaction; palladium catalysts.
Introduction
cyclisation ofcompound 1 under the conditions indicated gives
rise to the linear branched cyclic product 2, whilst the linear
product 3 (Scheme 1) is preferred when the reactants are not
tethered.[13]
The Heck electrophilic arylation ofalkenes has many merito-
rious features for synthetic chemistry.[1] A new C C bond is
À
formed under conditions that are tolerant of most functional
groups, frequently with predictable regiochemistry. A remark-
able range ofPd complexes catalyses the reaction through
cationic,[2] neutral,[3] or anionic intermediates.[4] Efficient
protocols for asymmetric inter- or intramolecular catalysis
have been developed.[5] Much recent effort has been devotedto
catalysts which operate with high turnover frequencies and
impressive productivity.[6] A healthy debate on the details of
mechanism, the structure ofreactive intermediates and the
role ofligands is underway. [7] Aspects ofthe reaction pathway
have been subject to DFT computational analysis.[8]
At the onset ofthis work we were interested in the potential
ofthe Heck reaction for introducing substituents in the 1- and
4- positions ofa tetrahydronaphthalene in a stereocontrolled
manner, starting with 1,2-dihydronaphthalene. A potential
short and stereocontrolled synthesis ofthe antidepressant
Sertraline provided an additional incentive for the work.[14]
The expectation was that an initial Heck reaction occurring in
branched fashion with aryl bonding to the a-position, would
generate an unstable alkylpalladium species likely to isomerise
to the remote benzylic position by a double Pd-H elimination/
readdition.[15] The alternative linear mode ofaddition would be
most likely unproductive, since the intermediate formed lacks
a cis-Pd-H elimination pathway. The investigation ofdifferent
catalysts to probe the regioselectivity, and the unexpected
outcome oflinear addition forms the basis ofthis investigation.
In Heck reactions ofstyrenes and other vinylarenes, the
question ofregioselectivity arises, the options being ofr-
mation ofa stilbene or a 1,1-diphenylethylene product. In
practice the result varies with reaction conditions in a manner
that is not clearly defined. With cationic intermediates, the
stoichiometric reaction occurs only in a linear direction; the
branched intermediate is not observed.[9,10] Nevertheless,
related studies indicate that a mixture ofthe two possible
regioisomers ofalkene product is ormf ed when
‡
PhPd(dppp) XÀ is reacted with styrene.[10] The main variable
is the solvent, which can change the reaction course from 95%
linear in 1:9 DMF:CH2Cl2 to only 65% linear in pure DMF
(X ˆ OTf). In addition, with X ˆ I or OAc, increasing the
likelihood ofcovalent intermediates, the proportion oflinear
isomer increases to ca. 80%. Catalytic Heck reactions of
styrenes under cationic catalyst control typically lead to 40%
branched product.[2a] In other cases the formation of branched
product is less pronounced,[11] or even absent.[12] It is clearly a
general feature of the arylation of vinylarenes, since the
Scheme 1. Conditions: (i) 10 mol % Pd(OAc)2, 20% PPh3; (ii) Cl2
Pd(PPh3)2, NaOAc, MeCN, 908C.
104
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Adv. Synth. Catal. 2002, 344, No. 1

Competing Regiochemical Pathways in the Heck Arylation of1,2-Dihydronaphthalene
FULL PAPERS
phosphine-free conditions developed by Jeffery,[17] the pro-
portion oflinear isomer 5c over branched isomer 4c was
dramatically higher when the alkene was present in substantial
excess. Closer examination indicates that this is only in part due
to changed regiospecificity, but also to partial disproportiona-
tion ofthe branched product to compounds 6 and 7 under the
reaction conditions. At low alkene concentrations, more
branched product is formed but the overall yield drops
considerably. There is good evidence that Pd nanoparticles
formed under turnover conditions are the active catalytic
species in the Jeffery phosphine-free catalysts.[21] Their pres-
ence could explain the tendency ofthe doubly benzylic product
4 to disproportionate following well-established heterogene-
ous or homogeneous Pd-catalysed pathways.[22] Hence the two
methods are complementary; under optimal conditions the
Jeffery method leads predominantly to 5, whilst the Herrmann
protocol leads to a significant excess of the branched product 4.
Results and Discussion
The Regiochemistry of Heck Reactions of
1,2-Dihydronaphthalene
At the outset ofthe work, two distinct palladium catalyst types
were identified; the phosphopalladocycles introduced by
Herrmann and co-workers and shown to be highly active in
the Heck chemistry ofsimple alkenes, [16] and alternatively the
phosphine-free catalysts used in the presence of phase-transfer
reagents and pioneered through Jeffery×s work.[17] The liter-
ature offers interesting examples where the latter elicits
unusual regiochemistry in the product compared to phos-
phine-containing catalysts.[18]
When the Heck reactant is an aryl halide or triflate and the
substrate is a styrene, the product may be a stilbene (linear
pathway) or 1,1-diarylethylene (branched pathway). Ifthe
alkene is monosubstituted, then the product ofan intermolec-
ular reaction is normally the E-stilbene,[19] with the exception
ofan unusual reductive arylation under base-free conditions
where the Z-isomer dominates.[20] The cases where significant
amounts of1,1-diarylethylene have been reported tend to
involve cationic palladium intermediates.[2a] Success requires
that the branched pathway is enjoined, but preliminary experi-
ments with preformed cationic catalysts and aryl triflates were
discouraging. Thus, a mixture ofPhOTfand 3,4-dihydronaph-
thalene reacted with Pd(OAc)2, (S)-BINAP and different
bases in toluene at 408C gave no evidence ofreaction atfer
several days. Attention was then shifted to neutral palladium
catalysts.
In common with other 1,2-disubstituted alkenes, the Pd-
catalysed reaction of1,2-dihydronaphthalene with aryl halides
proceeds much more sluggishly than the reaction ofmono-
substitutedalkenes. Two catalytic systems were discovered that
proved to be effective. First, the palladocycle catalysts
popularised through Herrmann×s work were investigated.[16]
Reactions with two different aryl electrophiles and varying
conditions (Scheme 2) are reported in Table 1. The desired
product 4a or 4b arising from a branched pathway is evident in
all cases, and is indeed the anticipated result ofdouble
isomerisation. It is accompanied, however, by a significant
competing pathway leading to the corresponding 3-aryl-1,2-
dihydronaphthalenes 5a and 5b, the formal linear pathway. The
proportion ofthe two products varies somewhat as the reaction
conditions are altered, so that it was never possible to achieve
complete dominance ofproduct 4. The best results were
obtained with a ten-fold excess of alkene, when the proportion
ofbranched product was signiifcantly higher, and the yield
better. When the reaction was carried out under the alternative
The Stereochemistry of the Linear Pathway Leading to
Compound 5
It is long established that Pd-Ar addition in the initial addition
step ofthe Heck reaction is cis-stereospecific.[23] Given that, it
is not immediately obvious how a Pd-H elimination leading to 5
can occur. Three possibilities need to be considered; firstly, the
process occurs by a trans-elimination pathway, secondly, an a-
elimination giving a Pd-carbene complex is followed by 1,2-
hydride migration and thirdly the configuration of the initially
formed Pd insertion product is inverted before elimination. All
three ofthese routes have been suggested in other palladium
catalyses. The circumstance that a Heck reaction cannot be
completed without a formal trans-elimination is not uncom-
mon, and Ikeda has reviewed examples recorded up to 1999 in
heterocycle synthesis.[24] There are two substantial categories
in his review, one where the final Pd alkyl is adjacent to a
carbonyl group (and can therefore epimerise by reversible
keto-enol tautomerism), and a second where the Pd alkyl is
benzylic. Whilst there is no direct mechanistic evidence in
these cases, Pd benzyls can access an h3-coordination geome-
Scheme 2. (i) Heck reaction; conditions as in Table 1.
Adv. Synth. Catal. 2002, 344, 104 109
Figure 1.
105

Kenji Maeda et al.
FULL PAPERS
Table 1.
[e]
Entry
Amount ofDihydronaphthalene
Solvent (temp)
Catalyst (mol % as Pd)
Combined yield of1- and 3-
Ratio of1- to 3-
1
2
3
4
5[a]
6[a]
3.0 eq.
3.0 eq.
3.0 eq.
3.0 eq.
10.0 eq.
10.0 eq.
CH3CN reflux
CH3CN[b] reflux
CH3CN[c] reflux
Toluene[b] reflux
None (1108C)
None (1108C)
A (1 mol %)
A (1 mol %)
B (2 mol %)
B (2 mol %)
B (2 mol %)
B (8 mol %)
36
35
13
36
32
59
33: 67
36: 64
29: 71
62: 38
75: 25
72: 28
[a]
Pr3N was used instead ofEt N.
Distilled under nitrogen.
Degassed under reduced pressure (commercial anhydrous grade).
Commercial anhydrous grade.
3
[b]
[c]
[d]
[e]
A: Prepared in situ from Pd(OAc)2 and (o-tol)3P.
; B: Commercial palladacycle from STREM.
try,[25] and a good analogy exists. Takacs and co-workers have
shown that the near-symmetrical allylpalladium complex 9
formed from the allylic carbonate precursor 8 is transformed
into the corresponding diene 10 by exclusive trans-elimination,
precluding Pd inversion.[26] An alternative possibility is indi-
cated by studies of cine-substitution in organotin cross-
couplings. Farina and co-workers have proposed a palladium
carbene mechanism to explain the formation of the rearranged
product 12 from stannane 11.[27] The closeness ofthese
structures to potential intermediates in the present chemistry
indicates that an experimental distinction between trans-
elimination and carbene mechanisms is necessary.
deuterium is not present at cis-H-2 or any other site in 4c
demonstrates that the classical mechanism of cis-PdAr addi-
tion to the alkene followed by Pd migration is upheld; the Pd
migrates much faster than inversion of configuration at C-2.
Experiments with 13a or 13b under Jeffery×s conditions
uphold the interpretation. The fact that 3-arylation occurs with
comparable facility using two widely different Pd catalyst
systems, and the deuterium is completely lost from C-2 in both
cases, indicates that the trans-elimination pathway is at the very
least more likely than Pd inversion followed by cis-elimina-
tion.[27e] It can be envisaged to occur through an E2 reaction of
the base, present in stoichiometric amount, with a Pd benzyl
that has an enhanced lifetime compared to related alkyls
because ofpartial or complete h3-association with the arene.
The regioisomer ratio is comparable for the two deuterated
reactants at comparable alkene concentrations. This indicates
the absence ofsignificant reversibility in the Pd-aryl addition
step, given that a primary isotope effect on the elimination step
would bias the reaction towards 4-arylation in the 3-d reactant
13b.
The synthesis ofthe two regioisomeric deuterium-labelled
alkenes 13a and 13b was carried out as shown in Scheme 3. In
separate experiments, they were subjected to coupling with 4-
FC6H4Br under the Herrmann-type conditions applied earlier.
No attempt was made to separate the two reaction products 4c
1
2
and 5c from one another, analysis by H and H NMR being
carried out on the TLC-purified mixture. As far as the linear
isomer 5c is concerned, the results were unequivocal since the
label at the 4-position (employing 13a) was completely
2
retained (peak in H NMR, CHCl3 at 6.8 ppm; absence of
this peak in 1H NMR). The label at the 3-position (employing
13b) was completely removed in the product within exper-
imental error (MS m/z 224, full retention of 6.8 ppm peak in the
1H NMR) (Scheme 2). The carbene mechanism delineated by
Farina can be ruled out on this evidence, since it would result in
an observable deuterium migration from the 3- to the 4-
position when 13b is the reactant. Further information stems
from the deuterium distribution in the branched product 4c,
where the deuterium label is completely retained in both
2
experiments. When 13a is the reactant, the H NMR shows
only a signal at 4.1 ppm; the corresponding H-1 signal of 5c is
absent from the 1H NMR spectrum. When 13b is the reactant,
2
the H NMR spectrum of 4c (d ˆ 2.66 ppm, CHCl3) demon-
strates that deuterium is retained in the product, and exclu-
sively associated with a single site. This is corroborated by the
1H NMR spectrum showing that the low-field component of
the diastereotopic CH2 at C-2 is absent. By nOe and COSY
calibration ofthe 1H NMR spectrum ofprotonated 4c, this is
indicated to be H-2 trans to the aryl group. The fact that
Scheme 3. Conditions: (i) DMSO, 1708C, 1 h; (ii) 1008C, toluene,
2 h; (iii) Bu4NCl, KOAc, Pd(OAc)2 [5 mol %], DMF, 808C, 18 h.
106
Adv. Synth. Catal. 2002, 344, 104 109

Competing Regiochemical Pathways in the Heck Arylation of1,2-Dihydronaphthalene
FULL PAPERS
1-Phenyl-1,2-dihydronaphthalene:
a
clear colourless oil; 1H NMR
Mechanistic Conclusions
(200 MHz; CDCl3): d ˆ 7.50 7.19 (8H, m), 6.97 (1H, d, J ˆ 7.4 Hz), 6.70
(1H, d, J ˆ 9.7 Hz), 6.19 6.10 (1H, m), 4.28 (1H, t, J ˆ 8.7 Hz), 2.82 2.74
(2H, m); 13C NMR (200 MHz; CDCl3): d ˆ 144.8, 138.2, 134.5, 128.8, 128.8,
Here we endeavour to address why the regiochemical course
should depend on the reaction conditions, and why two distinct
procedures for the Heck reaction give the opposite regio-
chemical preference, when run under the optimum condition
using excess alkene. This is counterintuitive, since expectation
is that the course ofarylation should be relatively weakly
influenced by ligands. Delivery of palladium to the 3-position
and formationof the 1-aryl isomer will be expected, in any ionic
mechanism because ofbenzylic charge stabilisation irrespec-
tive ofcharge. In experimentally defined cases, the Pd acts as
the nucleophilic partner in addition ofPd-Ar to the alkene. [28]
As a counterforce, the benzyl formed by Pd delivery to the 4-
position will be preferred if the stability of the oxidative
addition product is important. Broadly speaking, an early
transition state favours 1-arylation but a late transition state
favours 3-arylation on this basis.
How this should relate to the two catalytic protocols is
unclear. For the Jeffery catalyst case Pd nanoparticles formed
under turnover conditions are likely to be the active cata-
lysts.[21] The reactivity of these particles will be affected by
association of reactants at active surface sites, hence the effect
ofalkene concentration (high [alkene] masking the most
reactive early TS sites and leading to an increased proportion
of3-arylation?) on the regioselectivity is reasonable. With the
Herrmann catalyst system, the trend is towards increasing 1-
arylation at higher alkene concentration. That implies a change
in the nature ofthe catalyst, although other than indicating that
a higher coordination state ofalkene is increasingly involved,
the details remain elusive.
‡
128.4, 128.2, 127.5, 127.5, 127.1, 126.8, 126.5, 43.9, 32.0; MS (CI ): m/z ˆ 207
‡
(M ‡ 1).
3-Phenyl-1,2-dihydronaphthalene: white needles; mp 62 648C, (lit. 62
648);[31] 1H NMR (200 MHz; CDCl3): d ˆ 7.68 7.61 (2H, m), 7.52 7.32 (3H,
m), 7.29 7.21 (4H, m), 6.96 (1H, s), 3.05 (2H, t, J ˆ 8.2 Hz), 2.83 (2H, t, J ˆ
7.9 Hz); 13C NMR (200 MHz; CDCl3): d ˆ 141.4, 139.0, 135.1, 135.1, 128.7,
‡
127.6, 127.5, 127.2, 126.9, 125.4, 125.4, 124.6, 28.1, 26.3; MS (CI ): m/z ˆ 207
‡
(M ‡ 1, 34%), 206 (100), 128 (9).
1- and 3-(3,4-Dichlorophenyl)-1,2-dihydronaphthalene (4b
and 5b)
As above, but with 3,4-dichloroiodobenzene (2.729 g, 10 mmol) and freshly
distilled 1,2-dihydronaphthalene (3.906 g, 3.92 mL, 30 mmol) to yield
0.960 g ofa mixture of1-(3,4-dichlorophenyl)-1,2-dihydronaphthalene and
3-(3,4-dichlorophenyl)-1,2-dihydronaphthalene (35% yield, combined cou-
pling products). The ratio of1-(3,4-dichlorophenyl)-1,2-dihydronaphtha-
lene and 3-(3,4-dichlorophenyl)-1,2-dihydronaphthalene was determined to
be 36:64 by same method as above.
1-(3,4-Dichlorophenyl)-1,2-dihydronaphthalene: clear colourless oil;
1H NMR (300 MHz; CDCl3): d ˆ 7.36 7.01 (6H, m), 6.82 (1H, d, J ˆ
7.2 Hz), 6.54 (1H, d, J ˆ 9.6 Hz), 5.98 5.92 (1H, m), 4.08 (1H, t, J ˆ
8.1 Hz), 2.71 2.64 (1H, m), 2.58 2.53 (1H, m); 13C NMR (300 MHz;
CDCl3): d ˆ 144.9, 136.4, 133.8, 132.3, 130.3, 130.3, 130.2, 128.1, 127.8, 127.8,
‡
‡
127.5, 127.3, 126.4, 126.4, 42.8, 31.7; MS (CI ): m/z ˆ 275(M ‡ 1); HRMS:
‡
m/z calcd. for C16H12Cl2 (M ) 274.0316, found 274.0334.
3-(3,4-Dichlorophenyl)-1,2-dihydronaphthalene; white needles; mp 79
808C; 1H NMR (300 Hz; CDCl3): d ˆ 7.58 (1H, d, J ˆ 2.1 Hz), 7.41 7.31
(2H, m), 7.21 7.07 (4H, m), 6.82 (1H, s), 2.93 (2H, t, J ˆ 8.1 Hz), 2.66 (2H, t,
J ˆ 7.9 Hz); 13C NMR (300MHz; CDCl3): d ˆ 141.1, 136.1, 134.7, 134.0,
132.5, 130.8, 1302, 127.5, 127.3, 126.9, 126.9, 126.7, 125.7, 124.3, 27.9, 26.0; MS
‡
‡
‡
(CI ): m/z ˆ 275(M ‡ 1); HRMS: m/z calcd for C16H12Cl2 (M ) 274.0316,
found 274.0300.
Experimental Section
3-(4-Fluorophenyl)-1,2-dihydronaphthalene[32] (5c)
General
To a well-stirred suspension of tert-butylammonium chloride (933.5 mg,
3.35 mmol) and potassium acetate (330 mg, 3.35 mmol) in dry DMFover 4 ä
molecular sieves were successively added 1-bromo-4-fluorobenzene
(235 mg, 1.35 mmol), 1,2-dihydronaphthalene (1.75 g, 13.45 mmol) and
palladium acetate (15.1 mg, 0.013 mmol). The reaction mixture was stirred
at 808C for 18 hours under argon. Diethyl ether was added and the reaction
mixture was filtered through a Celite bed to remove palladium salts. The
organic phase was washed with water (2 Â 20 mL) followed by drying over
MgSO4 and the solvent and starting materials removed under vacuum. The
crude product purified by column chromatography using pentane as the
eluent. The clear liquid produced was identified as >96% 3-(4-fluorophen-
yl)-1,2-dihydronaphthalene (151 mg, 50%). The proton NMR, mass spec-
trum and GC trace ofthe product corresponded with those ofan authentic
sample, prepared from b-tetralone by reaction with 4-fluorophenylmagne-
sium bromide and acid-catalysed dehydration ofthe product: 1H NMR
(200 MHz, CDCl3): d ˆ 2.81 [2H, t, CH2CH ˆ , 3J(H,H) ˆ 8.0 Hz], 3.04 [2H,
t, CH2CH2CH ˆ , 3J(H,H) ˆ 8.0 Hz], 6.89 [1H, s, CH ˆ C(Ar)], 7.26 (6H, m,
See previous papers on related topics for full protocols of spectroscopic and
experimental procedures.[29]
1-Phenyl-1,2-dihydronaphthalene[30] and 3-Phenyl-1,2-
dihydronaphthalene[31] (4a and 5a)
Palladium acetate (45 mg, 0.2 mmol) and tri-o-tolylphosphine (243 mg,
0.8 mmol) were dissolved in acetonitrile (20 mL) under argon. The solution
was heated under reflux for 15 min, then iodobenzene (4.080 g, 2.24 mL,
20 mmol), freshly distilled 1,2-dihydronaphthalene (7.812 g, 7.84 mL,
60 mmol) and triethylamine (2.192 g, 4 mL, 29 mmol) were added to the
solution and the solution was heated under reflux for 48 h. The cooled
reaction mixture was diluted with diethyl ether (100 mL), poured into HCl
(aq, 1.0 M, 100 mL), then extracted with diethyl ether (2 Â 100 mL). The
combined organic layer was washed with brine (100 mL) and dried (MgSO4),
filtered and evaporated. Removing 1,2-dihydronaphthalene under vacuum,
‡
‡
Har), 7.58 (2H, m, Har); MS (EI ): m/z ˆ 224.19 (M ).
¾
then purification by flash column chromatography (Biotage cartridge silica
4-Deuterio-1,2-dihydronaphthalene[34] (13a)
[30]
gel, pentane only) gave 0.325 g of1-phenyl-1,2-dihydronaphthalene,
0.368 g of3-phenyl-1,2-dihydronaphthalene, [31] and 0.839 g oftheir unsepa-
rated mixture (37% yield, combined coupling products). The ratio of1-
phenyl-1,2-dihydronaphthalene and 3-phenyl-1,2-dihydronaphthalene was
1-Deuterio-2,3,4-trihydro-1-naphthol (3.3 g, 22.1 mmol) and DMSO
(25 mL) were placed in a dry Schlenk tube under argon and heated to
1708C for 1 h. The product was partitioned between water (100 mL) and
pentane and the organic layer separated, dried (MgSO4) and solvent
removed under vacuum. After purification by Kugelrohr distillation the
1
determined to be 33:67 by comparison of H NMR area (before purifica-
tion) of8-H of1-phenyl-1,2-dihydronaphthalene ( d ˆ 6.97, 0.33H, d, J ˆ
7.4 Hz) and 4-H of3-phenyl-1,2-dihydronaphthalene ( d ˆ 6.96, 0.67H, s).
Adv. Synth. Catal. 2002, 344, 104 109
107

Kenji Maeda et al.
FULL PAPERS
resulting clear liquid (2.12 g, 73%) was identified as 4-deuterio-1,2-
acetate (46 mg, 0.56 mmol) and 4 ä molecular sieves were added in a
Schlenk tube under argon. DMF (1 mL) was then added and the reaction
mixture was stirred at 808C for 18 hours. The crude product was purified as
before.
dihydronaphthalene; bp 328C/0.2 torr; IR (thin film): nmax ˆ 3052, 3014
(sp2CH), 2251 cmÀ1 (sp2C-D); 1H NMR (400 MHz, CDCl3): d ˆ 2.49 [2H, td,
3
CH2CH , 3J(H,H) ˆ 8.2 Hz, J(H,H) ˆ 4.4 Hz], 2.98 [2H, t, CH2CH2CH ,
ˆ
ˆ
J(H,H) ˆ 8.2 Hz], 6.20 [1H, tt, CD CH, 3J(H,H) ˆ 4.4 Hz, 3J(H,D) ˆ
3
ˆ
1.4 Hz], 7.20, 7.33 (4H, m, CAr); 13C NMR (400 MHz, CDCl3): d ˆ 25.8,
1
ˆ
30.2 (Csat), 130.1 [CD , t, J(C,D) ˆ 24 Hz], 128.5, 129.1, 129.5, 130.2, 131.2
‡
‡
Attempts at Asymmetric Heck Coupling Reactions
(CAr,Csp2), 136.7, 138.1 (CAr); MS (CI ): m/z ˆ 131 (M ).
Following Hayashi×s conditions,[15a] palladium acetate (2.2 mg, 0.01 mmol)
and (R)-BINAP (12.5 mg, 0.02 mmol) were dissolved in toluene (2 mL)
under argon. The solution was stirred at room temperature for 10 min, then
phenyl triflate (0.226 g, 162 mL, 1.0 mmol), freshly distilled 1,2-dihydro-
naphthalene (0.651 g, 653 mL, 5.0 mmol) and 2,6-di-tert-butyl-4-methylpyr-
idine (0.616 g, 3.0 mmol) or triethylamine (0.506 g, 697 mL, 5.0 mmol) were
added to the solution and stirred at 408C for 24 48 h. The same procedure
ofwork-up as above gave no coupling, and starting materials were
recovered.
3-Deuterio-1,2-dihydronaphthalene[34] (13b)
A dry Schlenk tube was charged with 2-deuterio-1,3,4-trihydro-2-naph-
thol[33] (3.78 g, 25.4 mmol), ethylamine (3.54 mL, 25.4 mmol) and dichloro-
methane (75 mL). Mesyl chloride (2.06 mL , 26.6 mmol) was then added
over a period of15 minutes at 0 8C. Awhite precipitate was formed, and the
reaction stirred for a further 90 min. The organic layer was washed with
water (3 Â 200 mL), dried over MgSO4 and solvent was removed under
vacuum. Mesylate (yield: 5.14 g, 83%) mp 58 59.58C; IR (KBr): nmax
ˆ
3024.5, 2972.0, 2936.3, 2892.5, 2192.8 (C D), 1340.1 (vs), 1166.3 cmÀ1 (vs);
1H NMR (400 MHz, CDCl3): d ˆ 2.20 [2H, t, CH2CH2CD(OMs), 3J(H,H) ˆ
Acknowledgements
2
3
6.5 Hz], 2.98 [2H, ABqt, CH2CH2CD(OMs) J(H,H) ˆ 17.0 Hz, J(H,H) ˆ
6.5 Hz], 3.06 (3H, s, CH3SO2), 3.18 [2H, ABq, CaromCH2CD(OMs),
2J(H,H) ˆ 17.0 Hz], 7.16 (4H, m, Har); 13C NMR (400 MHz, CDCl3): d ˆ
26.38, 29.30, 35.77, 39.20, 77.83 [CD(OMs), t, 1J(C,D) ˆ 23.4 Hz], 126.66,
We thank EPSRC for support and Tokyo Gas for leave of absence (to KM).
Johnson-Matthey provided a generous loan of palladium salts, and CASE
support for EJF. We thank Merck Inc. for an unrestricted research grant. Dr.
Barbara Odell was very helpful in the obtention of NMR spectra
‡
‡
126.89, 129.10, 129.70, 132.74 (q), 135.30 (q); MS (EI ): m/z ˆ 131 (M CH3
SO3H). The mesylate (5.14 g, 22.5 mmol) was placed in a dry Schlenk tube
under argon and dissolved in toluene (150 mL). To this solution was added
1,8-diazabicyclo[5.4.0]undec-7-ene (13.5 mL, 90.0 mmol) the mixture imme-
diately went green. The reaction was stirred for 2 hours at 1008C. After
cooling, the crude mixture was washed with 2 M HCl (3 Â 150 mL) and dried
over MgSO4. After removal of solvent under vacuum, the crude product was
purified by distillation. The clear liquid isolated was identified as 3-deuterio-
1,2-dihydronaphthalene; yield:1.67 g (56%); bp 318C/0.2 mbar; IR (thin
References and Notes
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film): nmax ˆ 3064.7, 3028.7, 3014.0, 2254.9 cmÀ1 (C C D); 1H NMR
ˆ
(400 MHz, CDCl3): dˆ 2.41 [2H, td, CH2CHˆ , 3J(H,H)ˆ 8.2 Hz, 4J(H,H) ˆ
3
2.0 Hz], 2.90 [2H, t, CH2CH2CH ˆ , J(H,H) ˆ 8.2 Hz], 6.57 [1H, m, CH ˆ
CD, 4J(H,H) ˆ 2.0 Hz, 3J(H,D) ˆ 1.5 Hz], 7.13, 7.21 (4H, m, Har); 13C NMR
(400 MHz, CDCl3): d ˆ 23.2, 29.7, 128.4 [CD ˆ , t, 1J(C,D) ˆ 24.2 Hz], 125.9,
‡
‡
126.5, 126.9, 127.6, 127.7,134.2 (q), 135.5 (q); MS (EI ): m/z ˆ 131 (M ).
Coupling of 4-Deuterio-1,2-dihydronaphthalene with 4-
Fluorobromobenzene under Jeffery Conditions
To a well-stirred suspension oftetrabutylammonium chloride (208 mg,
0.75 mmol) and potassium acetate (73 mg, 0.75 mmol) in 3 mL ofdry DMF
with 4 ä molecular sieves were successively added 4-fluorobromobenzene
(37 mL, 0.30 mmol), 4-deuterio-1,2-dihydronaphthalene (391 mL, 3.0 mmol)
and palladium acetate (3.5 mg, 5 mol %). The reaction mixture was stirred
under argon at 808C for 18 hours. After cooling, 5 mL of diethyl ether were
added and the mixture filtered through Celite. After removal of the solvent
and the starting material under vacuum, the crude product was purified by
preparative TLC (pentane) to afford 3-(4-fluorophenyl)-4-deuterio-1,2-
dihydronaphthalene; IR (thin film): nmax ˆ 3015.2, 2939.9, 2828.2, 2167.3
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(C C D), 1650.1 (C C), 1223.5 cmÀ1(C F, s); 1H NMR (400 MHz, CDCl3
): d ˆ 2.73 [2H, t, CH2CH ˆ , 3J(H,H) ˆ 8.0 Hz], 2.97 [2H, t, CH2CH2CH ˆ ,
3J(H,H) ˆ 8.0 Hz], 7.07, 7.17 (6H, m, Har), 7.51 (2H, m); 13C NMR (500 MHz,
CDCl3): d ˆ 26.40, 28.1, 115.29 [d, 2J(C,F) ˆ 21.3 Hz], 126.50, 126.64, 126.72,
127.02, 127.22, 137.50, 134.57 [d, 4J(C,F) ˆ 1.7 Hz], 137.19 [d, 3J(C,F) ˆ
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‡
‡
3.9 Hz], 162.19 [d, 1J(C,F) ˆ 245.0 Hz]; MS (EI ): m/z ˆ 225.19 (M ).
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1-Bromo-4-fluorobenzene under Herrmann Conditions
1-Bromo-4-fluorobenzene (55 mL, 0.51 mmol), 4-deuterio-1,2-dihydro-
naphthalene (100 mg, 0.76 mmol), Herrmann×s catalyst (4 mg, 1%), sodium
108
Adv. Synth. Catal. 2002, 344, 104 109

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109