Synthesis of 1-indanols and 1-indanamines by intramolecular palladium(0)-catalyzed C(sp3)-H arylation: Impact of conformational effects

Article abstract of DOI:10.1002/chem.201402907

A range of valuable 1-indanols and 1-indanamines containing a tertiary C1 atom were synthesized by intramolecular palladium(0)-catalyzed C(sp ³)-H arylation, despite unfavorable steric interactions. The efficiency of the reaction was found to correlate with the degree of substitution at C2, as expected from the Thorpe-Ingold effect. Additionally, the nature of the heteroatomic substituent at C1 had a marked influence on the diastereoselectivity at C1 and C2; indeed, 1-indanols and 1-indanamines were obtained with the opposite relative configuration. Analysis of the X-ray and DFT-optimized structures of the corresponding reactive intermediates provided useful insights into the subtle conformational effects induced by these substituents.

Full text of DOI:10.1002/chem.201402907

DOI: 10.1002/chem.201402907
Full Paper
&
CÀH Activation
Synthesis of 1-Indanols and 1-Indanamines by Intramolecular
Palladium(0)-Catalyzed C(sp3)ÀH Arylation: Impact of
Conformational Effects
Simon Janody,[a] Rodolphe Jazzar,[a] Arnaud Comte,[a] Philipp M. Holstein,[a] Jean-
Pierre Vors,[b] Mark J. Ford,[c] and Olivier Baudoin*[a]
Abstract: A range of valuable 1-indanols and 1-indanamines
containing a tertiary C1 atom were synthesized by intramo-
lecular palladium(0)-catalyzed C(sp3)ÀH arylation, despite un-
favorable steric interactions. The efficiency of the reaction
was found to correlate with the degree of substitution at C2,
as expected from the Thorpe–Ingold effect. Additionally, the
nature of the heteroatomic substituent at C1 had a marked
influence on the diastereoselectivity at C1 and C2; indeed, 1-
indanols and 1-indanamines were obtained with the oppo-
site relative configuration. Analysis of the X-ray and DFT-op-
timized structures of the corresponding reactive intermedi-
ates provided useful insights into the subtle conformational
effects induced by these substituents.
Introduction
Transition-metal catalysis has recently emerged as a powerful
tool to functionalize otherwise unreactive C(sp3)ÀH bonds.[1] In
this context, our group[2] and others[3] have been able to syn-
thesize an array of fused carbocycles and heterocycles by intra-
molecular palladium(0)-catalyzed arylation of unactivated
C(sp3)ÀH bonds from aryl halides. Among the fused carbocy-
cles, indanes and indanones have been obtained,[2b,d,e,g] but
only when a quaternary center was present at the C1 position
for indanes and at C2 for indanones (Scheme 1a). Indanols and
indanamines are important building blocks for the discovery of
new drugs and agrochemicals, as shown by the structures of
the anti-HIV drug indinavir sulfate,[4] the synthetic odorant
Magnolan,[5] or the herbicide indaziflam (Scheme 1c).[6]
Herein, we report the construction of 1-indanols and 1-in-
danamines by intramolecular palladium(0)-catalyzed C(sp3)ÀH
arylation, and address some of the previously observed limita-
tions with regard to substitution (Scheme 1b). In addition, dif-
ferences in reactivity and diastereoselectivity observed among
[a] Dr. S. Janody, Dr. R. Jazzar, A. Comte, P. M. Holstein, Prof. Dr. O. Baudoin
Universitꢀ Claude Bernard Lyon 1, CNRS UMR 5246
Institut de Chimie et Biochimie Molꢀculaires et Supramolꢀculaires
CPE Lyon, 43 Boulevard du 11 Novembre 1918
69622 Villeurbanne (France)
Scheme 1. Synthesis of indane compounds by intramolecular Pd0-catalyzed
C(sp3)ÀH arylation.
E-mail: olivier.baudoin@univ-lyon1.fr
[b] Dr. J.-P. Vors
Bayer SAS, 14 Impasse Pierre Baizet
69263 Lyon Cedex 09 (France)
the various reaction substrates are discussed by means of con-
formational analysis. This should allow better anticipation of
the outcome of related transformations.
[c] Dr. M. J. Ford
Bayer CropScience AG, Industriepark Hçchst, G836
65926 Frankfurt am Main (Germany)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201402907.
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Results and Discussion
Table 1. Optimization of the intramolecular C(sp3)ÀH arylation reaction
leading to 1-indanols.
Synthesis of 1-indanols
We first considered aryl bromides, such as 1a, which contains
a silyl-protected benzylic alcohol and two tertiary carbon
atoms at C1 and C2, as both synthetically relevant and chal-
lenging CÀH activation substrates (Figure 1). In the computed
Entry
Pd source/ligand[b]
[mol%]
Basic system[c]
[equiv]
GC yield of
2b[d] [%]
d.r.[e]
1
Pd(OAc)2 (5)/
PCy3 (10)[f]
Pd(OAc)2 (5)/
P(Cyp)3 (10)[f]
Pd(OAc)2 (5)/
PPh3 (10)
Pd(OAc)2 (5)/
P(o-tol)Ph2 (10)
Pd(OAc)2 (5)/
P(4-NMe2Ph)3 (10)
Pd(OAc)2 (5)/
P(4-CF3Ph)3 (10)
Pd(OAc)2 (5)
K2CO3 (1.1)/
PivOK (0.1)
K2CO3 (1.1)/
PivOK (0.1)
K2CO3 (1)/
PivOK (0.1)
K2CO3 (1)/
PivOK (0.1)
K2CO3 (1)/
PivOK (0.1)
K2CO3 (1)/
PivOK (0.1)
K2CO3 (1)/
PivOK (0.1)
K2CO3 (1)/
PivOK (0.1)
K2CO3 (1)/
PivOK (0.1)
K2CO3 (1)/
PivOH (0.3)
Na2CO3 (1)/
PivOH (0.3)
Rb2CO3 (1)/
PivOH (0.3)
Cs2CO3 (1)/
PivOH (0.3)
K2CO3 (1)/
PivOK (0.1)
52
10:1
9:1
7:1
–
2
46
3
63
Figure 1. Identification of the main issues in the reaction of model substrate
1a. The lowest energy conformer of 1a is shown (M06/6-31G**).
4
2
5
39
7:1
5:1
–
most stable conformation of 1a, the H1 hydrogen atom is ori-
ented toward the ortho Br atom to minimize allylic strain at
C1.[7] For CÀH activation to occur at the C3 or C3’ methyl
groups, the system has to rotate around the C(Ar)ÀC1 bond,
thereby increasing allylic strain at C1. Moreover, C1 and C2 are
tertiary and should exert moderate Thorpe–Ingold (angle com-
pression) effects on the system.[8] In addition to this reactivity
issue, the C3 and C3’ methyl groups of 1a are diastereotopic,
and the diastereoselectivity of the reaction should depend on
the rotational freedom of the C1ÀC2 bond in catalytic Pd
intermediates.
6
57
7
0
8
[Pd2(dba)3] (2.5)
[Pd(PPh3)4] (5)
[Pd(PPh3)4] (5)
[Pd(PPh3)4] (5)
[Pd(PPh3)4] (5)
[Pd(PPh3)4] (5)
[Pd(PPh3)4] (1)
0
–
9
66 (55)[g]
7:1
7:1
–
10
11
12
13
14
62
8
43
22
23
7:1
6:1
7:1
A survey of silyl protecting groups in the key C(sp3)ÀH acti-
vation reaction led to the identification of 1b with a triisopro-
pylsilyl (TIPS) group as the optimal substrate (Table 1). The
smaller triethylsilyl (TES) and tert-butyldimethylsilyl (TBS)
groups mainly gave ketone 5b, whereas the larger tert-butyldi-
phenylsilyl (TBDPS) group provided higher amounts of dehy-
drogenated product analogous to 4b.[2a,b] With the TIPS group,
the desired indane was obtained as the major product under
the same conditions, together with minor amounts of protode-
brominated product 3b, dehydrogenated product 4b, and
ketone 5b (2b/3b/4b/5bꢀ63:13:2:12). A screening of typical
phosphine ligands in combination with Pd(OAc)2 as the palladi-
um source revealed that simple triphenylphosphine was the
most efficient ligand, in a somewhat surprising manner
(Table 1, entries 1–3). Indeed, indane 2b was formed in 63%
yield (as determined by GC) and about 7:1 d.r. in favor of the
cis diastereoisomer when using PPh3 (Table 1, entry 3). This rel-
ative configuration was established after tetrabutylammonium
fluoride (TBAF)-mediated alcohol deprotection (77% yield)
by NOESY experiments and comparison with literature
precedents.[9]
[a] Lowest energy conformer of 2b (M06/6-31G**), H atoms of the TIPS
group are omitted for clarity. [b] Cy=cyclohexyl, Cyp=cyclopentyl, dba=
dibenzylideneacetone. [c] Piv=pivaloyl. [d] The yield was determined by
GC-MS analysis of the crude mixture by using hexadecane as a standard.
Yield of the isolated product in parentheses. [e] Ratio of cis/trans diaste-
reoisomers, as determined by GC-MS analysis of the crude mixture. [f] In-
troduced as the HBF4 salt. [g] The minor trans diastereoisomer was also
isolated in 8% yield.
rangement of Me and OTIPS substituents in the product. Trial-
kylphosphines, such as PCy3 and P(Cyp)3, which have been suc-
cessfully employed in previous syntheses of indanes and inda-
nones,[2d] gave lower yields, although with slightly higher dia-
stereoselectivities in the present case (Table 1, entries 1 and 2).
Modifying the steric bulk (Table 1, entry 4) or the s-donor char-
acter of PPh3 (Table 1, entries 5 and 6) did not improve the re-
action efficiency. It seems that the small size of PPh3 is benefi-
cial in the current system. Control reactions with Pd(OAc)2 or
[Pd2(dba)3] as the Pd source and without phosphine ligand
gave little substrate conversion and no indane formation
(Table 1, entries 7 and 8). The Pd(OAc)2/PPh3 in situ combina-
The cis orientation of the OTIPS and Me groups is somewhat
surprising at first glance. However, the computed structure of
2b (Table 1) shows that the bulky silyl group turns away from
the C2 methyl group, thereby sterically allowing the cis ar-
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tion could be replaced with [Pd(PPh3)4] with similar results
(Table 1, entry 9), and this well-defined, readily available com-
plex was chosen for subsequent studies. The combination of
potassium pivalate (10 mol%) and potassium carbonate
(1 equiv) provided both the most efficient and convenient
basic system,[2,3] among other combinations (Table 1, en-
tries 10–13). Finally, a lower yield of 2b was obtained at lower
catalyst loadings (Table 1, entry 14). Under optimal conditions
(Table 1, entry 9), cis-indane 2b and its trans diastereoisomer
were isolated in 55 and 8% yield, respectively.
action leading to indane 2c occurred with equal efficiency
(88% yield) from the corresponding aryl iodide, but the corre-
sponding chloride was unreactive with this catalyst. Analogous
substrates containing a cyclopropyl (1e) or methylcyclopropyl
(1 f) fragment underwent CÀH activation at the cyclopropane
ring, which gave rise to original fused and spirocyclic indanes
2e and 2 f, respectively, with a higher efficiency for the less
strained ring system (2 f).[10] Next, the generality of the method
with regard to substituents on the aromatic ring was evaluated
with tBu-containing substrates (R2 =R3 =Me). Products 2g–k
were obtained in high yield, including pyridine- and thio-
phene-fused cyclopentanes 2j and 2k.
The method was also applicable to 1-indanols protected
with a pivaloyl group (Scheme 2b, products 2l–o). However,
iPr-containing substrate 1l gave an unproductive 1:1 mixture
of cis and trans diastereoisomers (with 86% conversion) in con-
trast to its silyl-protected analogue 1b, thereby illustrating the
impact of the alcohol substituent on the reaction diastereose-
lectivity. Remarkably, with the more favorable tBu substituent
(2m), the catalyst loading could be reduced to 0.5 mol% with
similar efficiency, in contrast to results obtained with iPr-con-
taining substrate 1b (Table 1, entry 14). To the best of our
knowledge, such a low catalytic loading is unprecedented in
palladium(0)-catalyzed intramolecular C(sp3)ÀH arylation.[2,3] In
addition, a lactone precursor (1p) was successfully reacted to
give original tricyclic product 2p in good yield.
With the optimized conditions in hand, a range of protected
alcohols were evaluated as CÀH activation substrates
(Scheme 2). First, higher substitution at C2 correlated with
In light of the above observations, we sought a way to im-
prove the efficiency of the reaction leading to the least substi-
tuted indane systems. Consistent with previous observa-
tions,[2d] we found that isopropyl ketone 1q was not a compe-
tent C(sp3)ÀH arylation substrate, presumably due to the pres-
ence of an enolizable position (Scheme 3). In contrast, silyl
Scheme 2. Synthesis of 1-indanols. Yields in parentheses refer to the isolated
products. [a] Yield from the corresponding aryl iodide. [b] Ratio of (insepara-
ble) cis/trans diastereoisomers measured in the crude mixture.
Scheme 3. Intramolecular C(sp3)ÀH arylation of a silyl enol ether. The lowest
energy conformer of 1r is shown (M06/6-31G**); H atoms of the TIPS group
are omitted for clarity. LiHMDS=lithium hexamethyldisilazane, Tf=trifluoro-
methanesulfonyl.
a greater efficiency, as shown with aryl bromides 1b–d leading
to indanes 2b–d. The decreasing yields in the order 2c>2b>
2d correlated with increasing amounts of protodebrominated
product (see compound 3b; Table 1). This striking behavior
may be ascribed to the Thorpe–Ingold effect,[8] which should
favor the intramolecular CÀH activation process for substrates
such as 1c containing a quaternary C2 carbon atom. As a con-
sequence, it seems difficult to override the conformational bias
of lightly substituted substrates such as 1d, which do not ben-
efit from this effect and therefore remain very challenging
cases for this type of CÀH activation reaction. Notably, the re-
enol ether 1r derived from 1q provided cyclized product 2r in
very good yield under the optimized conditions. To the best of
our knowledge, this is the first case of organometallic C(sp3)ÀH
activation of an enol equivalent giving rise to functionalization
at the allylic position, while maintaining the integrity of the
enol group.[11] A simple treatment with TBAF provided inda-
none 6. Notably, cyclic silyl enol ether 2r is in its own right an
interesting substrate for asymmetric catalysis.[12] The increased
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efficiency of silyl enol ether 1r compared with alcohol 1b can
again be understood by conformational analysis. Indeed, the
C1=C2 double bond of 1r is now perpendicular to the ben-
zene ring in the DFT-optimized structure of 1r (Scheme 3), and
the C(Ar)ÀC1 bond can easily rotate to position the locked C3
methyl group close to the reaction center. In contrast, com-
pound 1b is less prone to undergo CÀH activation at C3 or C3’
because its C1 atom is sp3 hybridized and experiences allylic
strain.
In addition to indanamine 2t, substituted products 2v and
2w were obtained with lower yields (ca. 40%).[14] For the syn-
thesis of 2t–w, a catalyst loading of 10 mol% was required to
achieve complete conversion. In contrast, tBu-containing sub-
strate 1x gave rise to aminoindane 2x in high yield with
5 mol% Pd. This further illustrates the impact of substitution at
C2 on the reaction efficiency.
This method was successfully employed to access a known
intermediate in the synthesis of the herbicide indaziflam
(Scheme 5). In the key step, aryl bromide 1y underwent
Synthesis of 1-indanamines
We next investigated the reactivity of aryl bromides with an
amino substituent at C1 (Scheme 4). The nature of the nitro-
Scheme 5. Application to the synthesis of a precursor of the herbicide inda-
ziflam. Phth=phthalimidoyl.
C(sp3)ÀH arylation on a gram scale to give trans indanamine
2y in 55% yield. The latter underwent hydrazine-mediated de-
protection to give the known racemic 2-aminoindane inter-
mediate 6y.[6,15]
Structural analysis of reactive intermediates
A proposed catalytic cycle, based on previous studies[2,3] and
adapted to the current system, is shown in Scheme 6. Oxida-
tive addition of the aryl bromide to the active [Pd(PPh3)2] com-
plex leads to palladium(II) intermediate A, which undergoes
ligand substitution with potassium pivalate[3e] to give complex
B. C(sp3)ÀH activation from B through the now well-characteri-
zed[2c,d,3c,e,i] base-induced concerted metalation–deprotonation
(CMD) mechanism[16] affords six-membered palladacycle C.[17]
Scheme 4. Synthesis of 1-indanamines. Yields in parentheses refer to the iso-
lated products. [a] Ratio of (inseparable) cis/trans diastereoisomers measured
in the crude mixture. [b] With 10 mol% Pd instead of 5 mol%. [c] Thermal el-
lipsoids at 50% probability.[13]
gen substituents (R1, R2) was crucial to induce the desired in-
tramolecular C(sp3)ÀH arylation. Indeed, pivalamide (2s),
phthalimide (2t), and succinimide (2u) were the only substitu-
ents that gave appreciable amounts of indane product (e.g.,
no CÀH arylation occurred with NHBoc, NHTs, and N=CHPh
groups; Boc=tert-butyloxycarbonyl, Ts=tosyl). Among them,
compound 2t provided the highest efficiency and diastereose-
lectivity. Indeed, product 2t was isolated in moderate yield,
but complete trans diastereoselectivity, which was established
by X-ray diffraction analysis (Scheme 4). Similar to 1-indanols,
PPh3 was the most efficient ligand in this case and limited the
amount of protodebrominated side product. Surprisingly, op-
posite relative configurations were obtained for protected in-
danamine 2t (trans) and indanol 2b (cis). The diastereoselectiv-
ity was much lower with 2s, whereas the diastereoselectivity
was comparable but the efficiency was lower with 2u. More-
over, the trans diastereoselectivity observed for 2t seemed to
be essentially substrate-controlled, since it was not affected by
a change of ligand.
Scheme 6. Proposed catalytic cycle.
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Figure 2. X-ray structure of A1, obtained from the oxidative addition of 1t
to [Pd(PPh3)4], showing selected distances in ꢁ (thermal ellipsoids at the
50% probability level; H atoms of the PPh3 ligands are omitted for clarity).[13]
Figure 3. DFT-optimized (B3PW91/6-31G**) structure of pivalate complex B1,
showing selected distances in ꢁ (H atoms of the PPh3 ligands are omitted
for clarity).
Finally, ligand exchange between PivOH and PPh3 and reduc-
tive elimination provide the indane product and allow regener-
ation of the catalytically active species.
dral angle (see the Supporting Information for details), is simi-
lar to that of A1 (H1···Pd=2.55 ꢁ, H2···Hortho =2.26 ꢁ); in addi-
tion, H1 and H2 again have an anti relationship (H1-C1-C2-
H2=175.68). The 3-Me group is closer to the proximal pivalate
oxygen atom (C3···O=3.53 ꢁ) than the 3’-Me group (C3’···O=
4.63 ꢁ). Therefore, the 3-Me group is better positioned to un-
dergo CÀH activation by Pd-bound pivalate, which would give
the observed trans configuration between the C1-phthalimido
and 3’-Me groups in product 2t (Scheme 4). However, for CÀH
activation to take place, the system has to rotate around the
C(Ar)ÀC1 bond (clockwise in Figure 3) to decrease the distance
between the pivalate ligand and C3 (the shortest H3···O dis-
tance is 2.59 ꢁ in B1, and should be around 1.25 ꢁ at the tran-
sition state[3c,e,18]). The role of the relatively small PPh3 ligand,
which was optimal in the current study, might be to bring suf-
ficient flexibility to allow this bond rotation.
Oxidative addition complex A1 was isolated upon reaction
of aryl bromide 1t with stoichiometric amounts of [Pd(PPh3)4]
in benzene at reflux, and was crystallographically characterized
(Figure 2). Complex A1 displays a typical square-planar trans-
[PdArBrL2] structure, despite the presence of relatively Lewis
basic oxygen atoms on the phthalimide group. The H1 hydro-
gen atom is oriented toward Pd with a H1···Pd distance of
2.85 ꢁ and a dihedral angle of Pd-C(Ar)-C1-H1 of 32.68. This ar-
rangement reflects the minimization of allylic strain at C1, as
discussed previously. In addition, the H2 hydrogen atom is anti
to H1 (H1-C1-C2-H2=175.48) and points toward the hydrogen
at Cortho (H2···Hortho =2.16 ꢁ). This anti conformation seems to
be preferred as well in solution, as indicated by the relatively
3
large J(H1,H2) constant of 12 Hz observed by 1H NMR spec-
troscopy (CDCl3, 293 K).
Oxidative addition complex A2 was also isolated upon reac-
tion of aryl bromide 1b with a stoichiometric amount of
[Pd(PPh3)4], and was crystallographically characterized
(Figure 4). Interestingly, complex A2 adopts a significantly dif-
ferent conformation to A1 at C1 and C2. Indeed, the H1 atom
is still oriented toward Pd, but the H1···Pd distance is longer
Complex A1 seems to be a relevant catalytic intermediate.
Indeed, complex A1 was converted into 2t under the usual re-
action conditions and was successfully employed as a catalyst
instead of [Pd(PPh3)4] in the reaction of aryl bromide 1t
(Scheme 7).
The structure of pivalate complex B1, which is the next in-
termediate in the catalytic cycle leading to indanamine 2t
(Scheme 6), was optimized by DFT calculations (Figure 3). The
most stable conformation of B1 at C2, as deduced from poten-
tial energy surface scans by varying the C(Ar)-C1-C2-C3’ dihe-
Figure 4. X-ray structure of A2, which was obtained from the oxidative addi-
tion of 1b to [Pd(PPh3)4], showing selected distances in ꢁ (thermal ellipsoids
at the 50% probability level; H atoms of the TIPS group and the PPh3 li-
gands are omitted for clarity).[13]
Scheme 7. Experiments with stoichiometric (top) and catalytic (bottom)
complex A1. [a] Yield determined by GC. [b] Yield of the isolated product.
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(3.09 ꢁ) and the dihedral angle Pd-C(Ar)-C1-H1 is larger (48.68).
In addition, the H2 atom is now in a gauche relationship with
H1 (H1-C1-C2-H2=77.18) and also points toward Pd, with
a H2···Pd distance of 2.77 ꢁ. Similarly as above with complex
A1, this gauche conformation seems to be preserved in solu-
lecular CÀH activation due to 1,3-allylic strain. Furthermore, we
showed that substitution at C2 markedly affected the efficiency
of the reaction, which might be ascribed to the Thorpe–Ingold
effect. Additionally, the nature of the substituent at C1 had
a profound influence on the diastereoselectivity at C1/C2. On
the basis of X-ray and DFT-optimized structures of reactive in-
termediates, this effect seemed to originate in the switching
between anti and gauche conformations at C1 and C2, de-
pending on the C1 substituent. Overall, this study contributes
to improve our understanding of conformational effects that
affect reactivity and stereoselectivity in such intramolecular
C(sp3)ÀH activation reactions, and thereby should help to fur-
ther expand their scope to access a wide array of polycyclic
systems.
3
tion, as indicated by the very weak J(H1,H2) constant (H1 res-
1
onates as an apparent singlet) observed by H NMR spectros-
copy (CDCl3, 293 K). Thus, the NPhth and OTIPS groups, which
clearly have markedly different sterics—the former is rigid and
flat, whereas the latter has a parasol-like shape—induce a dif-
ferent staggered conformation at the C1ÀC2 bond.
The structure of the corresponding pivalate complex B2 was
computed in a similar manner as that used for B1 (Figure 5).
Acknowledgements
We thank Bayer CropScience AG, the Ministꢂre de l’Enseigne-
ment Supꢃrieur et de la Recherche, and the Institut Universi-
taire de France for financial support; Johnson Matthey PLC for
a loan of palladium salts; and CCIR-ICBMS (Universitꢃ Claude
Bernard Lyon 1) for the allocation of computational resources.
We are also grateful to E. Jeanneau (Centre de Diffractomꢃtrie
Henri Longchambon, UCBL) and P. Larini for X-ray diffraction
analyses and assistance with DFT calculations, respectively.
Figure 5. DFT-optimized (B3PW91/6-31G**) structure of pivalate complex B2,
showing selected distances in ꢁ (H atoms of the TIPS group and the PPh3 li-
gands are omitted for clarity).
Keywords: CÀC coupling · CÀH activation · conformation
analysis · palladium
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The lowest energy conformation of B2 is also similar to the
solid-state structure of oxidative addition complex A2, with H1
and H2 atoms in a gauche relationship (H1-C1-C2-H2=65.58).
Therefore, the conformation at C1 and C2 seems to be pre-
served in the first two steps of the catalytic cycle. From com-
plex B2, CÀH activation occurs preferentially at the 3’-Me
group, as deduced from the cis configuration of product 2b
(Table 1). However, unlike phthalimido complex B1, the 3-Me
and 3’-Me groups are now equidistant to the proximal oxygen
atom of the pivalate ligand (C3···O=4.17 ꢁ, C3’···O=4.18 ꢁ)
due to the gauche conformation at the C1ÀC2 bond. This con-
formational difference might be the origin of the reversal and
lower level of diastereoselectivity observed for 2b compared
with 2t. However, to test this hypothesis and gain additional
insight, one would need to analyze the transition states that
lead to both diastereoisomers for each type of product.
Conclusion
We successfully synthesized valuable 1-indanols and 1-indana-
mines with a tertiary benzylic carbon atom (C1) by intramolec-
ular palladium(0)-catalyzed C(sp3)ÀH arylation, which occurred
under operationally simple conditions. This is a particularly
challenging case compared with most previous systems,[2,3] be-
cause sp3 hybridization of the benzylic atom disfavors intramo-
Chem. Eur. J. 2014, 20, 11084 – 11090
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Full Paper
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insoluble material during the reaction. The protodebrominated product
was the only observed soluble compound in the reaction of 1t. In addi-
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2t was stable under the reaction conditions, with no change in the dia-
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Received: April 2, 2014
Published online on July 28, 2014
Chem. Eur. J. 2014, 20, 11084 – 11090
www.chemeurj.org
11090
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim