Synthesis of substituted naphthalenes via a catalytic ring-expansion rearrangement

Article abstract of DOI:10.1021/ol8019617

(Figure Presented) A new methodology for the preparation of substituted naphthalenes starting from readily available indenones, organometal reagents, and trimethylsilyldiazomethane via a catalytic rearrangement process is described. Hindered biaryl naphthalenes, including triortho-substituted biaryls, can be accessed through our method. Our results are consistent with a mechanism involving a benzobenzvalene intermediate.

Full text of DOI:10.1021/ol8019617

ORGANIC
LETTERS
2008
Vol. 10, No. 21
4855-4857
Synthesis of Substituted Naphthalenes
via a Catalytic Ring-Expansion
Rearrangement
Adam C. Glass, Benjamin B. Morris, Lev N. Zakharov,† and Shih-Yuan Liu*
Department of Chemistry, UniVersity of Oregon, Eugene, Oregon 97403
lsy@uoregon.edu
Received August 21, 2008
ABSTRACT
A new methodology for the preparation of substituted naphthalenes starting from readily available indenones, organometal reagents, and
trimethylsilyldiazomethane via a catalytic rearrangement process is described. Hindered biaryl naphthalenes, including triortho-substituted
biaryls, can be accessed through our method. Our results are consistent with a mechanism involving a benzobenzvalene intermediate.
The naphthalene unit constitutes an important structural motif
in biologically active molecules, in materials science, and
in organic synthesis (e.g., in chiral ligands).1 Correspond-
ingly, substantial effort has been devoted to the development
of synthetic methodologies for its construction. In addition
to metal-mediated coupling-based strategies,2,3 which furnish
substituted naphthalene derivatives from an existing naph-
thalene core, a number of alternative approaches have been
developed. These include cyclization/annulation-based syn-
theses (e.g., Diels-Alder cyclization,1 Do¨tz reaction,4 ring-
closing metathesis,5 annulations using alkynes,6 intramolec-
ular Lewis acid-catalyzed cyclizations)1,7 and rearrangements
of strained rings.8 Despite significant advances made to date,
novel methods for the synthesis of naphthalenes employing
unprecedented synthons are still highly desirable. In this
communication, we present a new methodology for the
preparation of substituted naphthalenes starting from readily
available indenones, organolithium/Grignard reagents, and
trimethysilyldiazomethane via a catalytic rearrangement
process (Scheme 1).
† Correspondence concerning X-ray crystallography should be directed
to Lev Zakharov. E-mail: lev@uoregon.edu.
Scheme 1. Synthesis of Naphthalenes from Indenones
(1) For a comprehensive review, see: de Koning, C. B.; Rousseau, A. L.;
van Otterlo, W. A. L. Tetrahedron 2003, 59, 7–36.
(2) Metal-Catalyzed Cross-Coupling Reactions; Diederich, F., Stang,
P. J., Eds.; Wiley-VCH: Weinheim, Germany, 2004
(3) Li, X.; Hewgley, B.; Mulrroney, C. A.; Yang, J.; Kozlowski, M. C.
J. Org. Chem. 2003, 68, 5500–5511
.
.
(4) Do¨tz, K. H.; Tomuschat, P. Chem. Soc. ReV. 1999, 28, 187–198.
(5) (a) Huang, K.-S.; Wang, E.-C. Tetrahedron Lett. 2001, 42, 6155–
6157. (b) van Otterlo, W. A. L.; Ngidi, E. L.; Coyanis, M.; de Koning,
C. B. Tetrahedron Lett. 2003, 44, 311–313.
We have been engaged in developing synthetic methods
that rearrange easily accessible precursors into valuable target
structures. In particular, we sought to provide alternative
routes toward naphthalene biaryls that might address some
of the limitations of conventional cross-coupling technolo-
gies.9
(6) (a) Huang, Q.; Larock, R. C. J. Org. Chem. 2003, 68, 7342–7349.
(b) Barluenga, J.; Va´zquez-Villa, H.; Ballesteros, A.; Gonza´lez, J. M. Org.
Lett. 2003, 5, 4121–4123. (c) Viswanathan, G. S.; Wang, M.; Li, C.-J.
Angew. Chem., Int. Ed. 2002, 41, 2138–2141. (d) Yoshikawa, E.; Radhakrish-
nan, K. V.; Yamamoto, Y. J. Am. Chem. Soc. 2000, 122, 7280–7286. (e)
Pena, D.; Pe´rez, D.; Guitia´n, E.; Castedo, L. J. Am. Chem. Soc. 1999, 121,
5827–8.
10.1021/ol8019617 CCC: $40.75
Published on Web 10/04/2008
2008 American Chemical Society

We envisioned that cyclopropyl carbinol10 intermediate
C (Scheme 2) could be poised to undergo a ring-expansion
2.13,14 The exo diastereomer has been isolated as the major
product, the structure of which has been determined by
single-crystal X-ray crystallography (eq 1).
Table 1 illustrates that addition of nucleophiles to ketones
2 can be readily accomplished with organolithiums (entry
Scheme 2
Table 1. Nucleophilic Addition to 2
entry R2
R1-M
product yield (%)a
drb
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
Ph-Li
3a
3b
3c
3d
3e
3f
3g
3h
3i
73
50
52
58
56
67
62
70
81
44
53
>95:5
>95:5
>95:5
>95:5
>95:5
>95:5
>95:5
74:26
>95:5
76:24
>95:5
4-MeO2CC6H4-MgX
4-MeOC6H4-MgBr
4-ClC6H4-MgBr
4-FC6H4-MgBr
2-MeC6H4-Li
rearrangement to furnish naphthalenes D in a regioselective
fashion. Intermediate C can be prepared from indenones A
via a straightforward two-step process, i.e., cyclopropanation
followed by nucleophilic addition. The salient feature of this
methodology is that the pivotal C-C coupling between R1
and the naphthalene core is accomplished through a simple
addition of a nucleophile to a carbonyl.11
1-napthyl-MgBr
Me Ph-Li
9
10
11
Me 2-MeC6H4-Li
Me 2-MeOC6H4-MgBr
Me 2,6-(MeO)2C6H3-Li
3j
3k
b
a Isolated yield. Determined by H NMR.
1
1) as well as with functionalized Grignard reagents (entries
2-5). More hindered ortho-substituted nucleophiles also
serve as suitable coupling partners (entries 6-7). Entries
8-11 of Table 1 show that the nucleophilic attack at the
more sterically demanding electrophile 2b is feasible as well,
even with a 2,6-disubstituted aryl nucleophile (entry 11).
With the exception of two examples (entries 8 and 10), only
one diastereomer has been observed for the nucleophilic
addition. We have structurally characterized the adduct
between ketone 2a and 1-naphthylmagnesium bromide, i.e.,
3g, via X-ray crystallography. The relative stereochemistry
of the structure is consistent with an approach of the
nucleophile opposite the blocking silylcyclopropane group.
We chose to optimize the synthesis of naphthalenes via
the proposed ring expansion rearrangement using substrate
3a. A survey of Lewis acids and solvents reveals that the
optimal reaction conditions involve 10 mol % of Eu(OTf)3
in 1,2-dichloroethane as solvent (see Supporting Information
for details). The presence of the silicon group is crucial. A
control experiment performed with a substrate bearing H in
place of SiMe3 under the optimized reaction conditions
produced very little of the desired naphthalene product.
Cyclopropyl carbinols 3 from Table 1 were subjected to
the optimized reaction conditions. Table 2 shows that our
catalytic ring-expansion rearrangement is compatible with
Treatment of indenones 112 with commercially available
trimethylsilyldiazomethane in the presence of a catalytic
amount of Pd(OAc)2 furnishes silylcyclopropanated adducts
(7) Shibata, T.; Ueno, Y.; Kanda, K. Synlett 2006, 411–414.
(8) For leading references, see: (a) Shao, L.-X.; Zhang, Y.-P.; Qi, M.-
H.; Shi, M. Org. Lett. 2007, 9, 117–120. (b) Hamura, T.; Suzuki, T.;
Matsumoto, T.; Suzuki, K. Angew. Chem., Int. Ed. 2006, 45, 6294–6296.
(c) Nishii, Y.; Yoshida, T.; Asano, H.; Wakasugi, K.; Morita, J.-i.; Aso,
Y.; Yoshida, E.; Motoyashiya, J.; Aoyama, H.; Tanabe, Y. J. Org. Chem.
2005, 70, 2667–2678.
(9) For examples of biaryl synthesis that do not involve cross-couplings,
see: (a) Perkins, J. R.; Carter, R. G. J. Am. Chem. Soc. 2008, 130, 3290–
3291. (b) Nishida, G.; Noguchi, K.; Hirano, M.; Tanaka, K. Angew. Chem.,
Int. Ed. 2007, 46, 3951–3954. (c) Kotnis, A. S.; Zhu, K.; Lotz, B. L.; Natalie,
K. J.; Simpson, J. H.; Kacusr, D.; Thurston, D.; Prasad, J. S.; Mathew, S.;
Singh, A. K. Chem. Ind. 2005, 104, 217–226.
(10) For a review of cyclopropanes in organic synthesis, see: Wong,
H. N. C.; Hon, M.-Y.; Tse, C.-W.; Yip, Y.-C. Chem. ReV. 1989, 89, 165–
198.
(11) Hatano, M.; Miyamoto, T.; Ishihara, K. Curr. Org. Chem. 2007,
11, 127–157.
(13) Aoyama, T.; Iwamoto, Y.; Nishigaki, S.; Shioiri, T. Chem. Pharm.
Bull. 1989, 37, 253–256
(14) For a review of silylcyclopropanes, see: Paquette, L. Chem. ReV.
1986, 86, 733–750
.
(12) Indenones 1 were prepared from the corresponding bromoindanones.
See Supporting Information for details.
.
4856
Org. Lett., Vol. 10, No. 21, 2008

tivity is observed for substrate 3j, which contains the
o-methoxyphenyl substituent (entry 3). Noteworthy is the
preparation of a tetraortho-substituted biaryl 4k from precur-
sor 3k, although the regioselectivity of the rearrangement is
only moderate (entry 4). We have determined the structure
of the rearrangement byproduct 5k via X-ray crystallography,
thus unambiguously establishing the connectivity of the 1,3-
disubstituted naphthalene regioisomer 5.15
Table 2. Catalytic Ring Expansion Rearrangement of 3
The presence of isomer 5 may provide some insight into
the possible mechanism of the rearrangement process. The
current mechanistic hypothesis for its formation involves
a benzobenzvalene intermediate 6 (Scheme 3).16 Breaking
entry
R1
product
yield (%)a
1
2
3
4
5
6
7
Ph
4a
4b
4c
4d
4e
4f
84
42
46
56
58
62
67
4-MeO2CC6H4
4-MeOC6H4
4-ClC6H4
4-FC6H4
2-MeC6H4
1-naphthyl
Scheme 3. Possible Intermediate for the Rearrangement
4g
a Isolated yield.
functionalized (entries 2-5) and hindered (entries 6 and 7)
R1 groups. We have also prepared a disubstituted naphthalene
4l in a regioselective fashion from the corresponding
precursor 3l derived from a ꢀ-substituted indenone (eq 2).
bond a in 6 produces the 1,2-disubstituted naphthalene 4,
whereas breaking bond b yields the 1,3-disubstituted
isomer 5.
In summary, we have developed a new method for the
synthesis of substituted naphthalenes based on a catalytic
ring-expansion rearrangement process. Starting from readily
available indenones, biaryl naphthalenes, including hindered
triortho-substituted ones, can be accessed in a few steps. Our
method provides an alternative to cross-coupling procedures
for the synthesis of biaryl naphthalenes, and it distinguishes
itself from coupling protocols by achieving the crucial C-C
bond-forming step through a simple nucleophilic addition
to a carbonyl. Our experimental observations are consistent
with a rearrangement mechanism involving a benzvalene-
like intermediate. Current efforts are geared toward obtaining
a better understanding of the reaction mechanism and
improving the substrate scope and reaction efficiency.
Interestingly, we discovered that precursors 3h-3k, which
are derived from an R-substituted indenone, produce a
mixture of naphthalene products 4 and 5 under our optimized
conditions (Table 3). The desired 1,2-disubstituted regio-
Table 3. Catalytic Ring Expansion of Hindered Precursors
Acknowledgment. Support has been provided by the
University of Oregon. This material is based upon work
supported by the National Science Foundation under Grant
No. DGE-0742540 (A.C.G.).
entry
R1
product
yield (%)a
4:5b
1
2
3
4
Ph
2-MeC6H4
2-MeOC6H4
2,6-(MeO)2C6H3
h
i
j
70
70
85
77
93:7
93:7
83:17
64:36
Supporting Information Available: Experimental pro-
cedures, compound characterization data, and CIF files for
structures 2a and 3g. This material is available free of charge
via the Internet at http://pubs.acs.org.
k
a Isolated yield of a mixture of 4 and 5. Determined by H NMR.
b
1
OL8019617
(15) See Supporting Information for details.
(16) (a) Christl, M. Angew. Chem., Int. Ed. Engl. 1981, 20, 529–546.
(b) Katz, T. J.; Roth, R. J.; Acton, N.; Carnahan, E. J. J. Org. Chem. 1999,
64, 7663–7664.
isomer 4 is formed in high selectivity for substrates 3h and
3i, furnishing di- and triortho-substituted biaryl naphthalenes
4 in good yield (entries 1 and 2). A diminished regioselec-
Org. Lett., Vol. 10, No. 21, 2008
4857