University of Groningen Carbon-carbon bond formations using organolithium reagents ... · 2018. 8....
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University of Groningen
Carbon-carbon bond formations using organolithium reagentsHeijnen, Dorus
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Chapter 6 : Nickel-Catalyzed Cross-Coupling of Organolithium
Reagents with (Hetero)Aryl Electrophiles
Nickel-catalyzed selective cross-coupling of aromatic electrophiles (bromides, chlorides,
fluorides and methyl ethers) with organolithium reagents is described in this chapter. The use
of a commercially available nickel N-heterocyclic carbene (NHC) complex allows the
reaction with a variety of (hetero)aryllithium compounds, including those prepared via metal-
halogen exchange or direct metallation, whereas a commercially available electron-rich
nickel-bisphosphine complex also readily converts alkyllithium species into the corresponding
coupled product. These reactions proceed rapidly (1h) under mild conditions (room
temperature) while avoiding the undesired formation of reduced or homocoupled products.
Part of this chapter was published in : D. Heijnen J. Gualtierotti, V. Hornillos, and B. L. Feringa Chem.
Eur. J. 2016, 22, 3991-3995
6.1 Introduction
In the ongoing search for more efficient, environmentally benign and economically
sustainable processes, current research in cross-coupling methodologies has shown a growing
interest in the use of earth-abundant metal-based catalysts.[1]
Although palladium is applied in
the majority of these processes, catalytic systems based on iron, nickel, or cobalt have proven
suitable alternatives in several cases. In particular, the use of nickel has witnessed a rapid
growth owing to its low cost and unique properties.[2]
Nickel undergoes oxidative addition
more readily than palladium although reductive elimination is correspondingly more
difficult.[2b,c]
Ni0/Ni
II catalytic cycles are well known,
[2c] but Ni
I and Ni
III oxidation states
[2d]
can be also accessed, allowing for different modes of reactivity and for radical mechanisms to
operate.
Scheme 6.1 Previous and current nickel and organolithium catalysis
Nickel has been extensively used in cross-coupling of organoboron and organozinc reagents
with organic halides (Scheme 6.1a).[3]
For example, a highly efficient nickel-catalyzed
method for the synthesis of heterobiaryls at low temperature described by the group of
Hartwig highlights the potential of nickel in Suzuki-Miyaura reactions.[4]
Since the early
reports by Kumada and co-workers in 1972, Grignard reagents in combination with nickel are
known to be effective in the cross-coupling with aryl halides,[5]
and these organometallic
reagents were also the first to be efficiently employed in reactions with the less reactive
aromatic ethers.[6a-c]
Various groups have further developed the use of Grignard reagents and
other nucleophiles, including organozinc and organoboron compounds, in nickel-catalyzed
cross-coupling with aryl[6d-f]
and benzyl ethers[6g]
(Scheme 6.1a). Additionally, nickel has also
been found to activate very strong C-F bonds.[7]
Thus, the coupling of aromatic fluorides with
organometallic compounds has been reported, although activated fluoroarenes or
polyfluorinated aromatic substrates are usually employed.[7c]
Some of these reactions suffer
from competing isomerization of the alkyl coupling partners.[7d]
In sharp contrast, the direct use of organolithium reagents, among the most versatile and
widely used reagents in organic synthesis,[8]
in nickel-catalyzed cross-couplings reactions has
been limited to the polymerization of lithiated (hetero)arenes,[9a,b]
the coupling of
(trimethylsilyl)methyllithium with aromatic ethers (Scheme 6.1b),[9c,d]
and the homo-coupling
of arylbromides.[9e]
Despite these important advances, a general method for the nickel-
catalyzed cross-coupling of alkyl and (hetero)aryllithium reagents with aryl(pseudo)halides
remains elusive.
Organolithium compounds[8]
are commercially available or readily accessible by lithium-
halogen exchange and they are often employed as precursors for other organometallic
compounds (Mg, B, Zn, Sn) used in cross-coupling reactions. Their direct use drastically
reduces the amount of byproducts with the light lithium halide being the only stoichiometric
reaction waste. Our group recently described the direct use of these reagents in palladium-
catalyzed cross-coupling under mild conditions of a wide variety of organic bromides,[10]
chlorides,[11]
and triflates,[12]
providing high yields and selectivities (Scheme 6.1c).[13]
Considering the advantages associated with the use of nickel-based catalytic systems, the
development of a general nickel-catalyzed cross-coupling with easily accessible
organolithium reagents will provide a highly desirable alternative to existing methodologies.
Moreover, since the palladium-catalyzed methods with these reagents are based on the use of
aryl bromides, chlorides, and triflates, we were interested in exploring the coupling of less
reactive fluorides and aromatic ethers, the latter being obtained from a pool of starting
materials entirely distinct from aryl halides.
Herein, we report that the use of a commercially available nickel N-heterocyclic carbene
(NHC) or bisphosphine complex allows for the selective cross-coupling of organolithium
compounds with aryl bromides, chlorides, fluorides, and methyl ethers in high selectivity
under mild conditions (RT) and within short reaction times (1h; Scheme 6.1d).
6.2 Optimization and scope
In preliminary studies, we focused on reactions between either nBuLi or PhLi and 1-
chloronaphthalene (1a) in toluene at rt (Table 6.1) Surprisingly, the use of [Ni(cod)2]
(cod=1,5-cyclooctadiene) which has previously been shown to be effective for the cross-
coupling of (trimethylsilyl)methyllithium with aryl ethers,[9c,d]
gave no conversion into the
desired products 2a or 3a. ( entries 1a,b). Adding a phosphine ligand such as 1,2-
bis(diphenylphosphino)ethane (dppe) to the nickel catalyst gave the same disappointing result
for nBuLi (entry 2a) and 51% conversion, along with dehalogenated side product 4a, for PhLi
(entry 2b).
Table 6.1 Reaction Optimization with nickel catalysts
Entrya R Catalyst Conv. (%)
b 2a/3a:
4a:5ab
1a
n-Bu
Ni(COD)2
2 -
1b Ph 0 -
2a
n-Bu
Ni(COD)2/dppe
3 -
2b Ph 51 53:47:0
3a n-Bu
NiCl2(DME)
5 -
3b Ph 39 85:15:0
4a
n-Bu
NiCl2(PPh3)2
40 42:40:18
4b Ph 30 90:10:0
5a n-Bu
NiCl2(PCy3)2
68 25:60:15
5b Ph >99 68:30:2
6a n-Bu
NiCl2(DME)/Xphos
69 15:46:23
6b Ph 33 67:33:0
7a n-Bu
NiCl2(dppe)
>99 93::7:0
7b Ph 86 73:25:2
8a n-Bu
NiCl2(dppf)
85 52:35:8
8b Ph 92 79:15:6
9a n-Bu
C1
>99 94:6:0
9b Ph >99 95:1:4
10a n-Bu
C2
36 11:89:0
10b Ph 98 58:42:0
11a n-Bu
C3
72 57:43:0
11b
Ph
>99 >99:0:0
11cc
>99 >99:0:0
11dd
>99 >99:0:0 (98% yield)
11ee
30 >99:0:0
12 n-Bu Pd-Peppsi-Ipent >99 86:14:0
[a] Conditions: n-Butyllithium (0.45 mmol, 1,6 M in hexanes diluted with toluene to a final concentration of 0.45 M) or
phenyllithium (0.45 mmol, 1.8 M solution in dibutyl ether diluted with toluene to a final concentration of 0.5 M) was added
to a solution of 2-chloronaphthalene (0.3 mmol) in toluene (1,5 mL) over 1 h. [b] Conversion and 2a/3a:4:5: ratios
determined by GC analysis. [c] Using 0.5 mol% of catalyst. [d] 10 mmol (1.63 g) scale reaction using 1.5 mol% of catalyst. [e]
using 0.25 mol% of catalyst.
Considering these results and the fact that [Ni(cod)2] requires rigorous air-free conditions,
hampering both large-scale applications and optimization efforts, we turned our attention to
nickel(II) catalysts. Low to moderate conversions and selectivities were observed when
[NiCl2(dme)] (dme=dimethoxyethane) or [NiCl2(PPh3)2] were used (entries 3a-4b). Using
more electron rich and bulky phosphines (PCy3[14]
or XPhos[15]
) resulted in higher conversion,
but the selectivity for 2a or 3a remained unsatisfactory (entries 5a-6b). Subsequently, we
investigated the effect of common bidentate phosphines, which have been reported to impart
high activity in related nickel-catalyzed cross-coupling reactions with other organometallics.
The use of [NiCl2(dppe)][16]
and [NiCl2(dppf)] (dppf=1,1'-bis(diphenylphosphino)ferrocene)4]
resulted in even higher conversions but dehalogenation remained substantial (entries 7a-8b).
Encouraged by these results, we studied variations in the ligand structure and we found that
the use of commercial nickel complex [NiCl2(depe)] (C1;
depe=bis(diethylphosphino)ethane17]
bearing a bidentate alkylphosphine, led to full
conversion in the reaction with both nBuLi and PhLi with excellent selectivity toward the
cross-coupled products 2a or 3a (entries 9a,b). The nitrogen-based tridentate ligand C2
(entries 10a,b)[18]
was not efficient for this transformation. Remarkably, the use of Pd-
PEPPSI-IPent (entry 12), as well as other palladium-based catalysts (not shown) in the
reaction of nBuLi gave rise to lower selectivity than that observed with the nickel catalyst C1.
We then explored the effectiveness of catalyst C1 with respect to a less reactive non-π-
extended aryl chloride, such as 1-butyl-4-chlorobenzene 1b (Scheme 6.2), but incomplete
conversion was observed in the case of PhLi, alongside a large amount of n-butylbenzene 4b.
As neither elevated nor lower temperatures improved this result, further screening of nickel
catalysts was carried out. We found that the use of commercially available nickel(II) complex
[NiCl2(PPh3)IPrC3,[9a]
bearing a N-heterocyclic carbene, was key to restoring the conversion
(87 % yield of isolated product) and selectivity (98:2) toward 2b. Catalyst C3 also gave full
conversion with high selectivity in the reaction of 1a with PhLi (Table 1, entry 11b), allowing
a decrease in the catalyst loading to 0.5 mol % (entry 11c). Moreover, when this reaction was
performed on a larger scale (10 mmol, 1.63g) in the presence of 1.5 mol % of catalyst C3, 2a
was still obtained as the exclusive product in excellent yield (98% isolated product). The use
of C3 in the reaction of 1a with nBuLi afforded the desired compound 3a, albeit with
decreased conversion and selectivity compared to C1 (Table 6.1, entry 11a).
With two optimized catalyst systems (C3 for (hetero)aryllithium and C1 for alkyllithium,
respectively) we examined the generality of this reaction. A broad range of aryl bromides,
chlorides, fluorides, and methoxyarenes could be coupled with PhLi, using C3 as catalyst
(Scheme 6.2). Polyaromatic compounds showed high reactivity and could be transformed into
the coupled products in good to high yields with excellent selectivity (2a, 2c-e). Substrates
containing two aromatic groups could also be transformed selectively (2f, X=Br, and 2g,
X=Br, F).
Scheme 6.2. Nickel-catalyzed cross-coupling of phenyllithium with (hetero)aryl (pseudo)halides. [a] Conditions:
Phenyllithium (0.75 mmol, 1.8 M solution in dibutyl ether diluted with toluene to a final concentration of 0.6
M) was added to a solution of organic (pseudo)halide (0.5 mmol) in toluene (1.5 mL) over 1 h. Isolated yields
after column chromatography. [b] Reaction performed at 0 °C.
It is important to note that high reactivity was also found for simple phenyl halides or methyl
ethers, regardless of the electronic nature or the leaving group employed (2i-o). As shown for
2g, 2j, and 2k, the presence of an ortho substituent did not significantly hamper the cross-
coupling. A substrate containing an olefin (1h) was also readily converted into the
corresponding product 2h with high selectivity (Scheme 2). Trifluoromethylated compounds,
which are very important in the agrochemical and pharmaceutical industries,[19]
were also
suitable substrates, furnishing the corresponding products 2l and 2m in moderate to good
yield. As expected, C-Br and C-Cl bonds are more reactive than a C-O bond, allowing the
selective coupling of 4-bromo- or 4-chloroanisole at 0°C, leaving the methoxy group
untouched (2n). Only dehalogenation was observed in the reaction of 3-bromo-N,N-
dimethylaniline 1o with PhLi. However, the corresponding chloride provided biaryl 2o in 45
% yield. A sulfur-containing heterocycle was also coupled, affording compound 2p with high
selectivity.
We next examined the compatibility of our catalytic system with the most efficient procedures
to access (hetero)aryllithium species, which include direct metalation[20]
and halogen--lithium
exchange[8]
(Scheme 6.3). Hindered bis-ortho-substituted (2,6-dimethoxyphenyl)lithium,
prepared by directed lithiation, undergoes cross-coupling with 1-chloronaphthalene and
electron-rich 4-bromoanisole providing biaryls 2q and 2r, without the need to increase the
temperature or reaction time. Moreover a methoxymethyl (MOM) protecting group could be
tolerated at the ortho position of the organolithium reagent, allowing for an easy ortho-
lithiation/cross-coupling sequence to afford the corresponding MOM-protected phenol (2s,
2t). Furyllithium, obtained by direct lithiation of furan, smoothly couples to provide
compounds 2u-w with good yields and high selectivities. Organolithium compounds, obtained
through halogen-lithium exchange, could also be used as exemplified in the preparation of 2x
and 2z.
Scheme 6.3. Nickel-catalyzed cross-coupling of (hetero)aryllithium reagents with aryl halides. Conditions: Aryl-
Li (0.75 mmol, diluted with toluene to reach 0.45 M concentration) was added to a solution of organic halide
(0.5 mmol) in toluene (1.5 mL) over 1 h. Selectivity 2 vs dehalogenated + homocoupled >90%. Isolated yields
after column chromatography.
Importantly, commercially available 2-thienyllithium, which, according to our previous
study,[10a]
requires the addition of stoichiometric amounts of tetramethylethylenediamine
(TMEDA) as activating agent and elevated temperatures, reacted with 1-chloro- and 1-
bromonaphthalene at room temperature without the use of any additive (2y).
With an efficient procedure for aryl-aryl cross-coupling in hand, we turned our attention to the
use of alkyllithium compounds , applying catalyst C1 (Table 6.2).[21]
A range of polyaromatic
chlorides and fluorides were regioselectively alkylated at position 1 or 2, indicating that
benzyne intermediates, formed through 1,2-elimination, are not involved.
Table 6.2. Nickel-catalyzed cross-coupling of alkyllithium compounds
Entry
a Aryl halide Alkyllithium
Yield (%)
b
1 (3a)
1-chloronaphthalene
EtLi 65
2 (3b) n-BuLi 78
3 (3c) n-HexLi 87
4 (3d) iPrLic
63
5 (3e)
2-chloroanthracene
EtLi 67
6 (3f) n-HexLi 39
7 (3g)
1-chloroanthracene
EtLi 94
8 (3h) n-BuLi 84
9 (3i) n-HexLi 85
10 (3j) iPrLic
44
11 (3k) CycloPrLi 66
12 (3b)
1-fluoronaphthalene
n-BuLi 76
13 (3a) EtLi 66
14 (3d) iPrLi 63
[a] Conditions: AlkylLi (0.45 mmol, diluted with Toluene to reach 0.45 M concentration) was added to a solution
of organic halide (0.3 mmol) in toluene (2 mL) over 1 h. GC selectivity >95%. [b] Isolated yields after column
chromatography. [c] GC selectivity > 80%.
No isomerization of the alkyl moiety and less than 5% of reduced product were observed
when primary alkyllithium reagents were employed, demonstrating that competing β-hydride
elimination/dissociation was almost completely inhibited. Importantly, the use of EtLi, which
was unreactive in our previous palladium-based systems, afforded the corresponding products
(3a, 3e, 3g) in good yields and nearly perfect selectivity. These results highlight how
alternative metals such as nickel, besides being inexpensive, can also display complementary
reactivity to palladium. The reaction using iPrLi, which contains an increased number of β-
hydrogen atoms, proceeds without isomerization, although a minor amount of the reduced
product was formed (entries 4 and 14).[22]
Cyclopropyllithium,[23]
prepared from cyclopropyl
bromide and lithium metal, also provided the coupled product with high selectivity without
any ring-opened side products (entry 11).[24]
6.3 Conclusions
In summary, we have described for the first time how a range of (hetero)aryl and alkyllithium
compounds can be employed in cross-coupling reactions with aryl bromides, chlorides,
fluorides, and aromatic ethers, by using nickel as catalyst. The reaction takes place under mild
conditions (RT) with a broad scope of organolithium compounds and substrates, enabling
transformations that were proven difficult with palladium catalysts, such as the cross-coupling
of alkyllithium reagents bearing β-hydrogen with aryl chlorides and the use of EtLi as a
coupling partner. The low cost and availability of both organolithium reagents and nickel
catalysts, together with the selectivity of the novel method presented herein, make it a
valuable alternative with lower environmental impact for atom-economic formation of C-C
bonds
6.4 References [1] a) B. Su, Z.-C. Cao, Z.-J. Shi, Acc. Chem. Res. 2015, 48, 886; b) A. A. Toutov, W.-B. Liu, K. N.
Betz, A. Fedorov, B. M. Stoltz, R. H. Grubbs,. Nature 2015, 518, 80; c) L. L. Schafer, P. Mountford,; W.
E. Piers, Dalton Trans. 2015, 44, 12027; d) Metal-Catalysed Cross-Coupling Reactions, 2nd ed., (Eds.:
A. de Meijere and F. Diederich), Wiley-VCH: Weinheim, 2004. Transition Metals for Organic Synthesis,
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[2] a) S. Z. Tasker, E. A. Standley T. F. Jamison, Nature 2014, 509, 299; b) Modern Organonickel
Chemistry Ed. Y. Tamaru, (Wiley-VCH, Weinheim, 2005.; c) T. T. Tsou, J. K. Kochi,. J. Am. Chem. Soc.
1979 101, 6319; d) J. Cornella, E. Gómez-Bengoa, R. Martin, J. Am. Chem. Soc. 2013, 135, 1997.
[3] For seminal reports using organoboron compounds see: a) S. Saito, M. Sakai, N. Miyaura,
Tetrahedron Lett. 1996, 37, 2993; b) S. Saito, S. Oh-tani, N. Miyaura, J. Org. Chem. 1997, 62, 8024;
For reviews see c) F.-S. Han, Chem. Soc. Rev. 2013, 42, 5270; d) J. Yamaguchi, K. Muto, K. Itami, Eur. J.
Org. Chem. 2013, 19; e) V. B. Phapale, D. J. Cárdenas Chem. Soc. Rev., 2009, 38, 1598; For recent
reports see f) X. Chen, H. Ke, G. Zou, ACS Catal. 2014, 4, 379.; g) S. Handa,; E. D. Slack,; B. H. Lipshutz,
Angew. Chem. Int. Ed. 2015, 54, 11994.
[4] S. Ge and J. F. Hartwig, Angew. Chem. Int. Ed. 2012, 51, 12837.
[5] See for example: Y.-C. Xu, J. Zhang, H.-M. Sun, Q. Shen Y. Zhang, Dalton Trans. 2013, 42,
8437.
[6] For seminal reports see: a) E. Wenkert, E. L. Michelotti, C. S. Swindell, J. Am. Chem. Soc. 1979,
101, 2246.; b) E. Wenkert, E. L. Michelotti, C. S. Swindell, M. Tingoli, J. Org. Chem. 1984, 49, 4894.; c)
J. W. Dankwardt, Angew. Chem. Int. Ed. 2004, 43, 2428. For selected reviews see: d) B. M. Rosen, K.
W. Quasdorf, D. A. Wilson, N. Zhang, A.-M. Resmerita, N. K. Garg, V. Percec, Chem. Rev. 2011, 111,
1346.; e) J. Cornella, C. Zarate, R. Martin, Chem. Soc. Rev., 2014, 43, 8081; f) M. Tobisu, N. Chatani,
Acc. Chem. Res. 2015, 48, 1717; For nickel-catalyzed cross-coupling reactions of benzylic ethers and
esters see: g) E. J. Tollefson, L. E. Hanna, E. R. Jarvo, Acc. Chem. Res. 2015, 48, 2344.
[7] a) For a recent example using B2nep2 as nucleophile see: X.-W. Liu, J. Echavarren, C. Zarate,
Ruben Martin J. Am. Chem. Soc. 2015, 137, 12470.; b) F. Zhu, Z.-X. Wang J. Org. Chem. 2014, 79,
4285. and references cited therein.; c) A. D. Sun, K. Leung, A. D. Restivo, N. A. LaBerge, H. Takasaki, J.
A. Love, Chem. Eur. J. 2014, 20, 3162.; d) H. Guo, F. Kong, K.-I. Kanno, J. He, K. Nakajima, T. Takahashi,
Organometallics 2006, 25, 2045.
[8] a) The Chemistry of Organolithium Compounds, Eds. Z. Rappoport, I. Marek, Wiley-VCH,
Weinheim, 2004; b) Lithium Compounds in Organic Synthesis, Eds. R. Luisi, V. Capriati, Wiley-VCH,
Weinheim, 2014.
[9] a) K. Fuji, S. Tamba, K. Shono, A. Sugie, A. Mori, J. Am. Chem. Soc. 2013, 135, 12208.; b) S. B.
Jhaveri, J. J. Peterson K. R. Carter, Macromolecules, 2008, 41, 8977; c) M. Leiendecker, C.-C. Hsiao, L.
Guo, N. Alandini, M. Rueping, Angew. Chem. Int. Ed. 2014, 53, 12912.; d) L. Guo, M. Leiendecker, C.-
C. Hsiao, C. Baumann, M. Rueping, Chem. Commun. 2015, 51, 1937.; e) S. B. Jhaveri, K. R. Carter,
Chem. Eur. J. 2008, 14, 6845.
[10] a) M. Giannerini, M. Fañanás-Mastral, B. L. Feringa, Nature Chem. 2013, 5, 667; b) M.
Giannerini, V. Hornillos, C. Vila, M. Fañanás-Mastral, B. L. Feringa, Angew. Chem. Int. Ed. 2013, 52,
13329; c) C. Vila, M. Giannerini, V. Hornillos, M. Fañanás-Mastral, B. L. Feringa, Chem. Sci. 2014, 5,
1361; d) V. Hornillos, M. Giannerini, C. Vila, M. Fañanás-Mastral, B. L. Feringa, Chem. Sci. 2015, 6,
1394.
[11] a) V. Hornillos, M. Giannerini, C. Vila, M. Fañanás-Mastral, B. L. Feringa, Org. Lett. 2013, 15,
5114; b) L. M. Castelló, V. Hornillos, M. Giannerini, C. Vila, M. Fañanás-Mastral, B. L. Feringa, Org.
Lett. 2015, 17, 62.
[12] C. Vila, V. Hornillos, M. Giannerini, M. Fañanás-Mastral, B. L. Feringa, Chem. Eur. J., 2014, 20,
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[13] For highlights, see: a) V. Pace and R. Luisi, ChemCatChem, 2014, 6, 1516. b) V. Capriati, F. M.
Perna A. Salomone, Dalton Trans. 2014, 43, 14204.
[14] G. C. Fu, Acc. Chem. Res. 2008, 41, 1555.
[15] R. Martin, S. L. Buchwald, Acc. Chem. Res. 2008. 41, 1461.
[16] a) B. M. Rosen, C. Huang,; V. Percec, Org. Lett. 2008, 10, 2597; b) N. V. Lukashev, G. V.
Latyshev, P. A. Donez, G. A. Skryabin, I. P. Beletskaya, Synthesis 2006, 533.
[17] E. L. Lanni, J. R. Locke, C. M. Gleave, A. J. McNeil, Macromolecules, 2011, 44, 5136.
[18] J. Wang, M. Sánchez-Roselló, J. L. Aceña, C. del Pozo, A. E. Sorochinsky, S. Fustero, V. A.
Soloshonok, H. Liu, Chem. Rev. 2013, 114, 2432.
[19] V. Snieckus, Chem. Rev. 1990, 90, 879.
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Stradiotto, Chem. Eur. J. 2012, 18, 9758.
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Organ, Angew. Chem. Int. Ed. 2012, 51, 12837.
[22] For a review on the relevance of arylcyclopropanes and their synthesis via cross-coupling see:
A. Gagnon, M. Duplessis, L. Fader, Org. Prep. Proced. Int. 2010, 42, 1.
[23] Full conversion was also obtained using aryl bromides although the presence of reduced
starting material was also observed in the reaction mixture.
Acknowledgements This work described in this chapter was carried out together with Dr. Valentin Hornillos and Dr. Jean
Baptiste Gualtierotti
6.5 Experimental section
A. General procedures:
Chromatography: Merck silica gel type 9385 230-400 mesh, TLC: Merck silica gel 60, 0.25 mm.
Components were visualized by UV and potassium permanganate staining. Conversion of the
reaction were determined by GC-MS (GC, HP6890: MS HP5973) with an HP1 or HP5 column (Agilent
Technologies, Palo Alto, CA). Mass spectra were recorded on an AEI-MS-902 mass spectrometer (EI+)
or a LTQ Orbitrap XL (ESI+). 1H- and 13C-NMR were recorded on a Varian AMX400 (400 and 101 MHz,
respectively) or a Varian VXR300 (300 and 75 MHz, respectively) using CDCl3 as solvent. Chemical
shift values are reported in ppm with the solvent resonance as the internal standard (CHCl3: δ 7.26
for 1H, δ 77.0 for 13C). Data are reported as follows: chemical shifts, multiplicity (s = singlet, d =
doublet, t = triplet, q = quartet, br = broad, m = multiplet), coupling constants (Hz), and integration.
All reactions were carried out under nitrogen or argon atmosphere using oven dried glassware and
using standard Schlenk techniques. Diethyl ether, tetrahydrofuran and toluene were used from the
solvent purification system (MBRAUN SPS systems, MB-SPS-800). n-Hexane was dried and distilled
over sodium. All starting aryl bromides, chlorides and fluorides as well as organolithium precursors
were commercially available from Aldrich, Alfa-Aesar, Acros or TCI Europe, unless otherwise
indicated. PhLi (1.8 M in n-Bu2O), n-BuLi (1.6 M in n-hexane), t-BuLi (1.7 M in pentane), EtLi (0.5 M in
benzene:cyclohexane), n-HexLi (0.7 M in pentane), 2-Thienyllithium (1.0 M in THF/hexanes) and i-PrLi
(2.3 M in hexane) were commercially available from Aldrich and were diluted to 0.45 M with dry
toluene before use. Pd-Peppsi-i-Pent, all nickel catalysts, except C3, and ligands were commercially
available from Aldrich. C3 was available from TCI Europe. All catalysts, ligands and reagents were
used as received without further purification.
B. Preparation of organolithium reagents:
4-Methoxy-phenyllithium
In a dry Schlenk flask 4-bromoanisole (623 μl, 5.0 mmol, 1.0 equiv) was dissolved in dry THF (5.55
mL, 0.90 M) and the solution was cooled down to -78 °C. t-BuLi (5.88 ml, 10 mmol, 2.0 equiv) was
added slowly and the solution was stirred for 1 h. Then the temperature of the solution was allowed
to reach room temperature and the solution of organolithium regents was used without further
dilution (final concentration 0.44 M).
Furyllithium
Furan (363 μl, 5.0 mmol, 1.0 equiv) was dissolved in THF (7.93 mL, 0.63 M) and the solution was
cooled down to -40 °C. n-BuLi (3.13 ml. 5 mmol, 1 equiv) was added slowly. Then the solution was
allowed to reach room temperature and stirred for 1 h and used without further dilution (final
concentration 0.45 M).
Cyclopropyllithium
In a dry Schlenk flask, lithium shot (63 mg, 9 mmol, 1.8 equiv) was suspended in dry ether (1.38 mL,
6.5 M) at room temperature. Then bromocyclopropane (401 μL, 5 mmol, 1 equiv) was dissolved in
ether (1.39 mL, 3.6 M) and added slowly over 30 min using a syringe pump. After the addition the
mixture was stirred for 15 min. The solution was then diluted before use with toluene (8.31 ml) to
reach a final concentration of 0.45 M.
2-Methoxymethoxy-phenyllithium.
In a dry Schlenk flask (methoxymethoxy)benzene1 (690 mg, 5.0 mmol, 1 equiv) was dissolved in dry
THF (15.15 mL, 0.33 M) and the solution was cooled down to -78 °C. t-BuLi (2.94 ml, 5 mmol, 1 equiv)
was added slowly and the solution was stirred for 1 h. Then the solution was allowed to reach room
temperature and used without further dilution (final concentration 0.28M).
2.6-Dimethoxyphenyllithium
In a dry Schlenk flask 1,3-dimethoxybenzene (657 μl, 5.0 mmol, 1.0 equiv) was dissolved in dry THF
(2.5 mL, 2 M) and the solution was cooled down to -10 °C. n-BuLi (3.13 ml. 5 mmol, 1 equiv) was
added slowly and the solution was stirred for 30 min. Then the solution was allowed to reach room
temperature. The solution was then diluted before use with toluene (5.48 ml) to reach a final
concentration 0.45 M.
C. General Procedures for the Cross-Coupling of Aryllithium Reagents with Arylhalides or
Arylmethoxides.
In a dry Schlenk flask, [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]triphenylphosphine nickel(II)
dichloride C3 (19.51 mg, 0.025 mmol, 5 mol%) and the substrate (0.5 mmol, 1 equiv) were dissolved
in dry toluene (1.5 ml, 0.33 M) and the mixture was stirred at room temperature. The corresponding
lithium reagent (0.75 mmol, 1.5 equiv) was slowly added over 1 h by syringe pump. When the
addition was completed a saturated aqueous solution of NH4Cl was added to the reaction and the
mixture was extracted three times with ethyl acetate. The organic phases were combined, washed
with brine, dried over sodium sulfate and evaporated to dryness under vacuum to afford the crude
product which was then purified by column chromatography.
D. General Procedures for the Cross-Coupling of Alkyllithium Reagents with Arylhalides.
In a dry Schlenk flask, dichloro[1,2-bis(diethylphosphino)ethane]nickel(II) C1 (7.0 mg, 0.021 mmol, 5
mol%) and the substrate (0.3 mmol, 1 equiv) were dissolved in dry toluene (2 ml, 0.15 M) and the
mixture was stirred at room temperature. The corresponding lithium reagent (0.45 mmol, 1.5 equiv)
was slowly added over 1 h by syringe pump. When the addition was completed a saturated aqueous
solution of NH4Cl was added to the reaction flask and the mixture was extracted three times with
ethyl acetate. The organic phases were combined, washed with brine, dried over sodium sulfate and
evaporated to dryness under vacuum to afford the crude product which was then purified by column
chromatography.
1 C. T. Vo, T. A. Mitchell, J. W. Bode, J. Am. Chem. Soc. 2011, 133, 14082-14089. 6
E. Experimental Details and Spectral Data of Compounds
2a) 1-phenylnaphthalene Purified by FCC using pentane. Yield: 88% (from 1-bromonaphthalene),
75% (from 1-fluoronaphthalene), 93% (from 1- chloronaphthalene [>85% GCMS, 9 to 1 mixture with
2-chloronaphthalene], isolated as a 90/10 mixture with 2-phenylnaphthalene) Molecular Formula:
C16H12 1H NMR (300 MHz, CDCl3) δ 7.97-7.91 (m, 2H), 7.91-7.86 (m, 1H), 7.58-7.41 (m, 9H). 13C NMR
(75MHz, CDCl3) δ 140.7, 140.2, 133.8, 131.6, 130.1, 128.2, 128.2, 127.6, 127.2, 126.9, 126.0, 126.0,
125.7, 125.4. Spectral data match those reported in the literature. 2
2b) 4-butyl-1,1'-biphenyl Purified by FCC using pentane. Isolated with trace biphenyl originating from
the commercial Ph-Li used. Yield: 87% Molecular Formula: C16H18 1H NMR (400 MHz, CDCl3) δ 7.68
(dd, J = 8.1, 3.9 Hz, 2H), 7.60 (d, J = 7.8 Hz, 2H), 7.51 (q, J = 7.2 Hz, 2H), 7.45-7.37 (m, 1H), 7.34 (d, J =
7.8 Hz, 2H), 2.74 (t, J = 7.6 Hz, 2H), 1.73 (p, J = 7.6 Hz, 2H), 1.49 (h, J = 7.6 Hz, 2H), 1.05 (t, J = 7.6 Hz,
3H). 13C NMR (101MHz, CDCl3) δ 142.0, 141.2, 138.5, 128.8, 128.7, 126.9, 126.9, 126.9, 35.3, 33.6,
22.4, 14.0. Spectral data match those reported in the literature.2
2c) 9-phenylphenanthrene Purified by FCC using pentane Yield: 82% Molecular Formula: C20H14 1H
NMR (300 MHz, CDCl3) δ 8.82 (dd, J = 8.3, 1.3 Hz, 1H), 8.77 (dd, J = 8.0, 1.5 Hz, 1H), 7.99 (dd, J = 8.3,
1.3 Hz, 1H), 7.94 (dd, J = 8.0, 1.5 Hz, 1H), 7.79-7.43 (m, 10H). 13C NMR (75MHz, CDCl3) δ 140.8, 138.7,
131.5, 131.1, 130.6, 130.0, 129.9, 128.6, 128.3, 127.5, 127.3, 126.9, 126.8, 126.5, 126.5, 126.4, 122.9,
122.5. Spectral data match those reported in the literature.3
2 B. L. Feringa, Org. Lett., 2013, 15, 5114-5117. 7 3 F. Glorius, Chem. Sci., 2015, 6, 1816-1824. 4 A. K. Mohanakrishnan, Eur. J. Org. Chem., 2015, 5099-5114.
2d) 2-phenylanthracene Purified by FCC using pentane. Yield: 43% Molecular Formula: C20H14 1H
NMR (300 MHz, CDCl3) δ 8.48 (s, 1H), 8.45 (s, 1H), 8.21 (s, 1H), 8.09 (d, J = 8.8 Hz, 1H), 8.06-7.98 (m,
2H), 7.82-7.74 (m, 3H), 7.56-7.44 (m, 4H), 7.41 (t, J = 7.3 Hz, 1H). 13C NMR (75MHz, CDCl3) δ 141.0,
137.8, 132.1, 131.9, 131.8, 130.9, 128.9, 128.7, 128.2, 128.1, 127.4, 127.3, 126.6, 126.0, 125.7, 125.5,
125.5, 125.4. Spectral data matcher known literature reference.4
2e) 2-phenylnaphthalene Purified by FCC using pentane. Yield: 76% Molecular Formula: C16H12 1H
NMR (400 MHz, CDCl3) δ 8.10 (d, J = 1.9 Hz, 1H), 8.00-7.88 (m, 3H), 7.84-7.74 (m, 3H), 7.54 (tt, J = 6.5,
2.5 Hz, 4H), 7.46-7.39 (m, 1H). 13C NMR (101MHz, CDCl3) δ 141.2, 138.4, 133.7, 132.7, 128.9, 128.5,
128.2, 127.7, 127.5, 127.4, 126.3, 126.0, 125.8, 125.6. Spectral data match those reported in the
literature. 2
2f) 1,1':4',1''-terphenyl Purified by preparatory layer chromatography (PLC Silica gel 60 F254, 2mm)
using pentane. Yield: 61% Molecular Formula: C18H14 1H NMR (300 MHz, CDCl3) δ 7.68 (s, 4H), 7.67-
7.62 (m, 4H), 7.51-7.42 (m, 4H), 7.36 (t, J = 7.4 Hz, 2H). 13C NMR (75MHz, CDCl3) δ 140.9, 140.3, 129.0,
127.6, 127.5, 127.2. Spectral data match those reported in the literature . 5
2g) o-Terphenyl Purified by preparatory layer chromatography (PLC Silica gel 60 F254, 2mm) using
pentane. Yield: 61% (from 4-bromobiphenyl), 56% (from 4-fluorobiphenyl) Molecular Formula: C18H14 1H NMR (300 MHz, CDCl3) δ 7.43 (s, 4H), 7.26-7.17 (m, 6H), 7.17-7.11 (m, 4H). 13C NMR (75 MHz,
CDCl3) δ 141.4, 140.5, 130.5, 129.8, 127.8, 127.4, 126.4. Spectral data match those reported in the
literature.6
5 J.-X. Wang, Adv. Synth. Catal., 2008, 350, 315-320. 9 6 SDBS database No. 1198 (http://sdbs.db.aist.go.jp, National Institute of Advanced Industrial Science and
Technology, 30.07.2015).
2h) (E/Z)-4-methoxy-4'-(prop-1-en-1-yl)-1,1'-biphenyl The reaction was run with 7.5 mol% of
catalyst and at 40°C. Purified by FCC using pentane/dichloromethane (95:5-90:10). 1-bromo-4-(prop-
1-en-1-yl)benzene was used as a 1:1 mixture of E/Z isomers and the product was obtained as a 1:1
mixture of E/Z isomers. 7 Yield: 56% Molecular Formula: C16H16O 1H NMR (300 MHz, CDCl3) δ 7.64-
7.48 (m, 4H), 7.40 (d, J = 8.5 Hz, 1H) , 7.39 (d, J = 8.5 Hz, 1H), 7.01 (d, J = 8.8 Hz, 1H) , 6.99 (d, J = 8.8
Hz, 1H), 6.55-6.40 (m, 1H), 6.29 (dq, J = 15.7, 6.5 Hz, 0.45H), 5.84 (dq, J = 11.5, 7.2 Hz, 0.55H), 3.87 (s,
1.5H), 3.87 (s, 1.5H), 1.98 (dd, J = 7.2, 1.8 Hz, 1.6H), 1.93 (d, J = 6.5 Hz, 1.4H). 13C NMR (75MHz, CDCl3)
δ 159.1, 159.0, 139.0, 138.7, 136.3, 136.0, 133.4, 133.3, 130.6, 129.4, 129.2, 127.9, 127.8, 126.7,
126.6, 126.3, 126.1, 125.5, 114.1, 114.1, 55.3, 18.5, 14.7. HRMS: Calculated for C16H17O [M+H]+
225.1270; found 225.1274.
2i) 4-methyl-1,1'-biphenyl Purified by FCC using pentane. Isolated as a 70:30 mixture (GCMS) with
biphenyl originating from commercial phenyl lithium. Yield: 43% (from 4-fluorotoluene), 39% (from
4-methoxytoluene). Molecular Formula: C13H12 1H NMR (400 MHz, CDCl3) δ 7.67-7.59 (m, 5H), 7.56-
7.50 (m, 3H), 7.51-7.42 (m, 5H), 7.41-7.31 (m, 2H), 7.31-7.24 (m, 2H), 2.42 (s, 3H). 13C NMR (101MHz,
CDCl3) δ 141.1, 138.3, 137.0, 129.5, 128.7, 127.0, 127.0, 127.0, 21.1. Spectral data match those
reported in the literature.8
2j) 2-methyl-1,1'-biphenyl Purified by FCC using pentane. Isolated as a 78:22 mixture (GCMS) with
biphenyl originating from the commercial phenyl lithium. Yield: 94% Molecular Formula: C13H12 1H
NMR (400 MHz, CDCl3) δ 7.68 (d, J = 7.6 Hz, 1H), 7.56-7.46 (m, 3H), 7.46-7.38 (m, 3H), 7.38-7.29 (m,
4H), 2.36 (s, 3H). 13C NMR (101MHz, CDCl3) δ 155.1, 141.9, 135.3, 130.3, 129.8, 129.2, 128.0, 128.0,
126.7, 125.7, 20.5. Spectral data match those reported in the literature. 8
k) 2,4-dimethyl-1,1'-biphenyl Purified by FCC using pentane. Isolated as a 75:25 mixture (GCMS) with
biphenyl originating from the commercial phenyl lithium. Yield: 94% Molecular Formula: C14H14 1H
NMR (400 MHz, CDCl3) δ 7.68-7.62 (m, 1H), 7.53-7.33 (m, 2H), 7.27-7.13 (m, 1H), 2.40 (s, 3H), 2.22 (s,
1H). 13C NMR (101MHz, CDCl3) δ 142.6, 142.3, 141.3, 137.2, 134.0, 129.4, 128.9, 128.8, 128.0, 127.7,
127.3, 127.2, 126.6, 125.3, 20.8, 17.0. Spectral data match those reported in the literature. 9
2l) 3-(trifluoromethyl)-1,1'-biphenyl Purified by preparatory layer chromatography (PLC Silica gel 60
F254, 2mm) using pentane. Yield: 51% Molecular Formula: C13H9F3 1H NMR (300 MHz, CDCl3) δ 7.89
(s, 1H), 7.85-7.79 (m, 1H), 7.71-7.57 (m, 4H), 7.57-7.41 (m, 3H). 13C NMR (75MHz, CDCl3) δ. 142.1,
139.8, 131 (q, J = 31.8 Hz), 130.4, 129.3, 129.0, 128.1, 127.2, 124.2 (q, J = 272.1 Hz), 124.0 (m)
Spectral data match those reported in the literature10 .
2m) 4-(trifluoromethyl)-1,1'-biphenyl Purified by FCC using pentane. Yield: 88% (from 1-bromo-4-
(trifluoromethyl)benzene), 81% (from 1-chloro-4- (trifluoromethyl)benzene), 25% (1-fluoro-4-
(trifluoromethyl)benzene). Molecular Formula: C13H9F3 1H NMR (300 MHz, CDCl3) δ 7.70 (s, 4H), 7.64-
7.59 (m, 2H), 7.52-7.45 (m, 2H), 7.45-7.38 (m, 1H). 13C NMR (75MHz, CDCl3) δ 144.7, 139.8, 129.0,
128.2, 127.4, 127.3, 125.7, 125.6. Spectral data match those reported in the literature. 2
2n) 4-methoxy-1,1'-biphenyl Purified by FCC using pentane. Yield: 86% (From 4-bromoanisole), 66%
(from 4-chloroanisole). Molecular Formula: C13H12O 1H NMR (300 MHz, CDCl3) δ 7.65-7.50 (m, 4H),
7.52-7.40 (m, 2H), 7.39-7.29 (m, 1H), 7.07-6.93 (m, 2H), 3.87 (d, J = 1.7 Hz, 3H). 13C NMR (75MHz,
CDCl3) δ 159.2, 140.8, 133.8, 128.7, 128.2, 126.7, 126.7, 114.2, 55.3. Spectral data match those
reported in the literature. 2
7 K. U. Ingold, J. Am. Chem. Soc., 2002, 124, 6362-6366. 10
8 Z. Zhang, Angew. Chem. Int. Ed., 2015, 54, 4079-4082.
9 J. Dupont, Org. Lett., 2000, 2, 2881–2884. 10 W. Su, Angew. Chem. Int. Ed., 2015, 54, 2199 –2203. 12
2o) N,N-dimethyl-[1,1'-biphenyl]-3-amine Purified by FCC using Pentane/Toluene (75:25). Yield: 45%
Molecular Formula: C14H15N 1H NMR (300 MHz, CDCl3) δ 7.69-7.61 (m, 2H), 7.53-7.44 (m, 2H), 7.43-
7.33 (m, 2H), 7.00-6.92 (m, 2H), 6.82-6.72 (m, 1H), 3.07 (s, 6H). 13C NMR (75 MHz, CDCl3) δ 150.7,
142.2, 142.1, 129.3, 128.5, 127.3, 127.0, 116.0, 111.7, 111.6, 40.7. Spectral data match those
reported in the literature. 2
2p) 3-phenylbenzo[b]thiophene Purified by FCC using pentane. Yield: 65% Molecular Formula:
C14H10S 1H NMR (400 MHz, CDCl3) δ 7.96-7.89 (m, 2H), 7.63-7.57 (m, 2H), 7.53-7.46 (m, 2H), 7.46-7.36
(m, 4H). 13C NMR (101MHz, CDCl3) δ 140.7, 138.1, 137.9, 136.0, 128.7, 127.5, 124.4, 124.3, 123.4,
122.9, 122.9. Spectral data match those reported in the literature. 12
2q) 1-(2,6-dimethoxyphenyl)naphthalene Purified by FCC using pentane. Yield: 45% Molecular
Formula: C18H16O2 1H NMR (400 MHz, CDCl3) δ 7.90 (m, 2H), 7.58 (dd, J = 8.2, 7.0 Hz, 1H), 7.55-7.34
(m, 5H), 6.75 (d, J = 8.2 Hz, 2H), 3.66 (s, 6H). 13C NMR (101MHz, CDCl3) δ 158.4, 133.5, 132.7, 132.6,
129.1, 128.2, 128.0, 127.4, 126.0, 125.5, 125.4, 125.34, 117.6, 104.1, 55.9. Spectral data match those
reported in the literature. 13
2r) 2,4',6-trimethoxy-1,1'-biphenyl Purified by FCC using pentane. Yield: 30% Molecular Formula:
C15H16O3 1H NMR (300 MHz, CDCl3) δ 7.42-7.15 (m, 3H), 7.12-6.87 (m, 2H), 6.68 (d, J = 8.3 Hz, 2H),
3.87 (s, 3H), 3.77 (s, 6H). 13C NMR (75MHz, CDCl3) δ 158.3, 157.8, 131.9, 128.3, 126.1, 119.1, 113.2,
104.2, 55.9, 55.1. Spectral data match those reported in the literature. 14
11 M. Nakamura, J. Am. Chem. Soc., 2007, 129, 9844-9845. 12 S. Oi, Org. Lett., 2012, 14, 6186-6189. 14 13 B. L. Feringa, Angew. Chem. Int. Ed., 2013, 52, 13329-13333. 14 A. Wagner, Org. Lett., 2007, 9, 1781-1783. 15
2s) 1-(2-(methoxymethoxy)phenyl)naphthalene Purified by FCC using pentane. Yield: 72% Molecular
Formula: C18H16O2 1H NMR (400 MHz, CDCl3) δ 7.90-7.75 (m, 2H), 7.59 (d, J = 8.3 Hz, 1H), 7.50 (t, J =
7.5 Hz, 1H), 7.44 (t, J = 7.5 Hz, 1H), 7.41-7.32 (m, 3H), 7.28 (d, J = 8.3 Hz, 1H), 7.23 (d, J = 6.6 Hz, 1H),
7.11 (t, J = 7.5 Hz, 1H), 4.97 (d, J = 6.8 Hz, 1H), 4.93 (d, J = 6.8 Hz, 1H), 3.18 (s, 3H). 13C NMR (101MHz,
CDCl3) δ 154.8, 137.0, 133.3, 132.1, 131.9, 130.6, 129.0, 128.0, 127.6, 127.2, 126.4, 125.6, 125.5,
125.3, 121.9, 115.1, 94.6, 55.9. Spectral data match those reported in the literature. 2
2t) 2,4',6-trimethoxy-1,1'-biphenyl Purified by FCC using pentane. Yield: 30% Molecular Formula:
C15H16O3 1H NMR (400 MHz, CDCl3) δ 7.56-7.44 (m, 2H), 7.34 (dd, J = 7.6, 1.8 Hz, 1H), 7.32-7.25 (m,
1H), 7.24- 7.20 (m, 1H), 7.15-7.04 (m, 1H), 7.01-6.92 (m, 2H), 5.14 (s, 2H), 3.87 (s, 3H), 3.42 (s, 3H). 13C NMR (101MHz, CDCl3) δ 158.7, 154.2, 131.5, 131.0, 130.8, 130.6, 128.2, 122.3, 115.7, 113.5, 95.1,
56.1, 55.3. Spectral data match those reported in the literature. 15
2u) 2-(4-methoxyphenyl)furan Purified by FCC using pentane. Yield: 73% Molecular Formula:
C11H10O2 1H NMR (400 MHz, CDCl3) δ 7.61 (d, J = 8.2 Hz, 2H), 7.43 (s, 1H), 6.93 (d, J = 8.2 Hz, 1H), 6.56-
6.48 (m, 1H), 6.45 (m, 1H), 3.84 (s, 3H). 13C NMR (101MHz, CDCl3) δ 159.0, 154.0, 141.4, 125.2, 124.0,
114.1, 111.5, 103.4, 55.3. Spectral data match those reported in the literature. 16
2v) 2-(anthracen-2-yl)furan Purified by FCC using pentane. Yield: 65% Molecular Formula: C18H12O 1H
NMR (400 MHz, CDCl3) δ 8.43 (s, 1H), 8.38 (s, 1H), 8.31 (s, 1H), 8.00 (m, 3H), 7.75 (d, J = 8.8 Hz, 1H),
7.56 (s, 1H), 7.52-7.38 (m, 2H), 6.81 (d, J = 3.2 Hz, 1H), 6.60-6.50 (m, 1H). 13C NMR (101MHz, CDCl3) δ
154.1, 142.5, 132.2, 131.8, 131.6, 130.8, 128.7, 128.2, 128.1, 127.4, 126.5, 126.2, 125.6, 125.4, 122.3,
121.8, 111.9, 106.0. Spectral data match those reported in the literature. 17
15 B. L. Feringa, Org. Lett., 2015, 17, 62-65. 16 16 B. L. Feringa, Chem. Eur. J., 2014, 20, 13078-13083. 17 C.-M. Che, Org. Lett., 2006, 8, 325-328. 17
2w) 2-(naphthalen-2-yl)furan Purified by FCC using pentane. Yield: 43% Molecular Formula: C14H10O 1H NMR (300 MHz, CDCl3) δ 8.17 (s, 1H), 8.00-7.69 (m, 4H), 7.58-7.37 (m, 3H), 6.79 (d, J = 3.4 Hz, 1H),
6.54 (dd, J = 3.4, 1.8 Hz, 1H). 13C NMR (75MHz, CDCl3) δ 154.1, 142.3, 133.6, 132.7, 128.4, 128.2,
128.2, 127.8, 126.5, 125.9, 122.3, 122.1, 111.8, 105.6. Spectral data match those reported in the
literature. 16
2x) 1-(4-methoxyphenyl)naphthalene Purified by FCC using pentane. Yield: 70% Molecular Formula:
C17H14O 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 8.4 Hz, 1H), 7.94 (d, J = 8.2 Hz, 1H), 7.88 (d, J = 8.2 Hz,
1H), 7.58-7.54 (m, 1H), 7.52 (dd, J = 8.4, 1.6 Hz, 1H), 7.50-7.43 (m, 4H), 7.07 (d, J = 8.6 Hz, 2H), 3.92 (s,
3H). 13C NMR (101MHz, CDCl3) δ 159.0, 139.9, 133.9, 133.2, 131.9, 131.1, 128.3, 127.4, 126.9, 126.1,
125.9, 125.7, 125.4, 113.8, 55.4. Spectral data match those reported in the literature. 18
2y) 2-(naphthalen-1-yl)thiophene Purified by FCC using pentane. Yield: 79% (From 1-
chloronaphtalene), 89% (From 1-bromonapththalene) Molecular Formula: C14H10S 1H NMR (400 MHz,
CDCl3) δ 8.35-8.25 (m, 1H), 7.98-7.93 (m, 1H), 7.91 (dt, J = 8.2, 1.2 Hz, 1H), 7.64 (dd, J = 7.1, 1.2 Hz,
1H), 7.60-7.51 (m, 3H), 7.48 (dd, J = 5.1, 1.2 Hz, 1H), 7.31 (dd, J = 3.5, 1.2 Hz, 1H), 7.24 (dd, J = 5.1, 3.5
Hz, 1H). 13C NMR (101MHz, CDCl3) δ 141.8, 133.8, 132.4, 131.9, 128.4, 128.3, 128.2, 127.4, 127.2,
126.4, 126.0, 125.7, 125.6, 125.2. Spectral data match those reported in the literature. 16
2z) 2-(4-methoxyphenyl)naphthalene Purified by FCC using pentane/dichloromethane (90:10-85:15).
Yield: 80% Molecular Formula: C17H14O 1H NMR (300 MHz, CDCl3) δ 8.04 (d, J = 2.0 Hz, 1H), 7.99-7.83
(m, 3H), 7.76 (dd, J = 8.5, 1.9 Hz, 1H), 7.73-7.66 (m, 2H), 7.61-7.38 (m, 2H), 7.15-6.88 (m, 2H), 3.90 (s,
3H). 13C NMR (75MHz, CDCl3) δ 159.4, 138.3, 133.9, 133.7, 132.4, 128.5, 128.5, 128.2, 127.7, 126.3,
125.8, 125.5, 125.1, 114.4, 55.5. Spectral data match those reported in the literature. 19
18 L. X. Shao, J. Organomet. Chem., 2011, 696, 3741-3744. 18 19 B. Jiang, Org. Lett., 2015, 17, 1942-1945. 19
3a) 1-ethylnaphthalene Purified by FCC using pentane. Yield: 66% (from 1-fluoronaphthalene), 65%
(isolated as a 88 to 12 mixture with 2-isopropylnaphthalene when starting from 1-
chloronaphthalene, >85% GCMS, 9 to 1 mixture with 2- chloronaphthalene) Molecular Formula:
C12H12 1H NMR (300 MHz, CDCl3) δ 8.12 (q, J = 8.3 Hz, 1H), 7.92 (d, J = 7.1 Hz, 1H), 7.77 (d, J = 8.3 Hz,
1H), 7.62-7.44 (m, 3H), 7.41 (d, J = 7.1 Hz, 1H), 3.18 (d, J = 7.9 Hz, 2H), 1.45 (t, J = 7.8 Hz, 3H). 13C NMR
(75MHz, CDCl3) δ 140.2, 133.8, 131.8, 128.7, 126.4, 125.8, 125.6, 125.4, 124.8, 123.7, 25.9, 15.0.
Spectral data match those reported in the literature. 20
3b) 1-butylnaphthalene Purified by FCC using pentane. Yield: 76% (from 1-fluoronaphthtalene), 78%
(from 1- chloronaphthalene [>85% GCMS, 9 to 1 mixture with 2-chloronaphthalene], 87 to 13
mixture with 2-isopropylnaphthalene) Molecular Formula: C14H16 1H NMR (300 MHz, CDCl3) δ 8.12-
8.06 (m, 1H), 7.88 (dd,J = 8.1, 1.6 Hz, 1H,), 7.74 (d, J = 8.1 Hz, 1H), 7.57-7.47 (m, 2H), 7.43 (dd, J = 8.1,
7.0 Hz, 1H), 7.36 (dd, J = 7.0, 1.3 Hz, 1H), 3.25-2.87 (m, 2H), 1.86- 1.67 (m, 2H), 1.50 (h, J = 7.4 Hz, 2H),
1.01 (t, J = 7.4 Hz, 3H). 13C NMR (75MHz, CDCl3) δ 139.0, 133.9, 131.9, 128.7, 126.4, 125.9, 125.6,
125.5, 125.4, 123.9, 33.0, 32.85, 22.9, 14.1. Spectral data match those reported in the literature. 21
3c) 1-hexylnaphthalene Purified by FCC using pentane. Starting from commercially available 1-
chloronaphthalene (>85% GCMS, 9 to 1 mixture with 2-chloronaphthalene) Yield: 87% (9 to 1 mixture
with 2-hexylnaphthalene) Molecular Formula: C16H20 1H NMR (300 MHz, CDCl3) δ 8.11 (dd, J = 8.3, 1.5
Hz, 0.82H), 7.91 (dd, J = 7.8, 1.8 Hz, 0.9H), 7.88-7.80 (m, 0.34H), 7.76 (d, J = 8.1 Hz, 0.77H), 7.67 (s,
0.10H), 7.60-7.49 (m, 1.78H), 7.49-7.42 (m, 1H), 7.38 (dd, J = 6.9, 1.2 Hz, 0.9H), 3.20-3.04 (m, 2H),
2.90-2.71 (m, 0.27H), 1.88-1.70 (m, 2H), 1.57-1.46 (m, 2H), 1.44-1.30 (m, 4H), 1.07-0.89 (m, 3H). 13C
NMR (75MHz, CDCl3) δ 139.0, 133.9, 131.9, 128.7, 127.9, 127.7, 127.6, 127.4, 127.4, 126.4, 126.3,
125.8, 125.8, 125.6, 125.5, 125.3, 124.9, 123.9, 36.1, 33.1, 31.8, 31.4, 30.8, 29.5, 29.0, 22.7, 14.1.
Spectral data match those reported in the literature. 22
20 Z.-J. Shi, J. Am. Chem. Soc., 2008, 130, 3268-3269. 20
21 B. L. Feringa, Nature Chemistry, 2013, 5, 667-672. 22 1-hexylnaphthalene: Z.-J. Shi, Chem. Commun., 2013, 49, 7794-7796
3d) 1-isopropylnaphthalene Purified by FCC using pentane. Starting from commercially available 1-
chloronaphthalene (>85% GCMS, 9 to 1 mixture with 2-chloronaphtalene) Yield: 63% (85 to 15
mixture with 2-isopropylnaphthalene) Molecular Formula: C13H14 1H NMR (300 MHz, CDCl3) δ 8.17 (d,
J = 8.4 Hz, 0.85H), 7.92-7.86 (m, 1H), 7.86-7.79 (m, 0.3H), 7.77- 7.71 (m, 0.85H), 7.59-7.41 (m, 4H),
3.80 (hept, J = 6.7 Hz, 0.85H), 3.21-3.00 (m, 0.15H), 1.45 (d, J = 6.9 Hz, 5.1H), 1.39 (d, J = 6.9 Hz, 0.9H). 13C NMR (75MHz, CDCl3) δ 144.6, 133.9, 131.3, 128.9, 127.9, 127.8, 127.6, 126.3, 125.8, 125.8, 125.7,
125.6, 125.6, 125.2, 125.0, 124.1, 123.3, 121.7, 28.5, 23.9, 23.5. Spectral data match those reported
in the literature. 23
3e) 2-Ethylanthracene Purified by FCC using pentane. Isolated as a 90:10 mixture with anthracene.
Yield: 67% (74% as a 90:10 mixture with anthracene) Molecular Formula: C16H14 1H NMR (300 MHz,
CDCl3) δ 8.41 (s, 1H), 8.37 (s, 1H), 8.07-7.99 (m, 2H), 7.97 (d, J = 8.7 Hz, 1H), 7.79 (s, 1H), 7.52-7.44 (m,
2H), 7.38 (dd, J = 8.7, 1.6 Hz, 1H), 2.89 (q, J = 7.6 Hz, 2H), 1.41 (t, J = 7.6 Hz, 3H). 13C NMR (75MHz,
CDCl3) δ 141.1, 132.0, 131.8, 131.2, 130.5, 128.2, 128.1, 128.0, 127.3, 125.9, 125.4, 125.2, 124.9,
124.9, 29.2, 15.1. Spectral data match those reported in the literature. 24
3f) 2-hexylanthracene Purified by FCC using pentane. Isolated as an 90:10 mixture with anthracene.
Yield: 39% (43% as an 90:10 mixture with anthracene) Molecular Formula: C20H22 1H NMR (300 MHz,
CDCl3) δ 8.40 (s, 1H), 8.36 (s, 1H), 8.08-7.98 (m, 2H), 7.96 (d, J = 8.7 Hz, 1H), 7.77 (s, 1H), 7.53-7.42 (m,
2H), 7.36 (dd, J = 8.7, 1.7 Hz, 1H), 2.83 (t, J = 7.7 Hz, 2H), 1.86-1.67 (m, 2H), 1.51-1.25 (m, 6H), 1.00-
0.82 (m, 3H). 13C NMR (75MHz, CDCl3) δ 139.8, 132.0, 131.8, 131.2, 130.5, 128.1, 128.0, 128.0, 127.5,
125.9, 125.7, 125.3, 125.2, 124.9, 36.3, 31.8, 31.0, 29.1, 22.6, 14.1. HRMS: Calculated for C20H23O
[M+H]+ 263.1794; found 236.1792.
23 For both 1 & 2-isopropylnaphthalene see: B. L. Feringa, Chem. Sci., 2014, 5, 1361-1367. 24 Y. Pan, Tetrahedron, 2007, 63, 5071-5075 22
3g) 1-ethylanthracene Purified by FCC using pentane. Contains trace amounts anthracene. Yield: 94%
Molecular Formula: C16H14 1H NMR (300 MHz, CDCl3) δ 8.62 (s, 1H), 8.44 (s, 1H), 8.13-7.95 (m, 2H),
7.88 (d, J = 8.4 Hz, 1H), 7.52- 7.31 (m, 4H), 3.27 (q, J = 7.5 Hz, 2H), 1.49 (t, J = 7.5 Hz, 3H). 13C NMR
(75MHz, CDCl3) δ 140.1, 132.2, 131.5, 131.3, 130.5, 128.5, 127.9, 126.9, 126.7, 125.3, 125.2, 125.2,
123.7, 122.4, 26.0, 14.7. HRMS: Calculated for C16H15 [M+H]+ 207.1168; found 207.0801.
3h) 1-butylanthracene Purified by FCC using pentane. Isolated as a 95:5 mixture with anthracene 23
Yield: 80% (84% as an 95:15 mixture with anthracene) Molecular Formula: C18H18 1H NMR (300 MHz,
CDCl3) δ 8.62 (s, 1H), 8.44 (s, 1H), 8.13-7.95 (m, 2H), 7.89 (d, J = 8.4 Hz, 1H), 7.53, 7.45 (m, 2H), 7.44-
7.30 (m, 2H), 3.23 (t, 2H), 2.04-1.78 (m, 2H), 1.64-1.41 (m, 2H), 1.04 (t, J = 7.3 Hz, 3H). 13C NMR
(75MHz, CDCl3) δ 138.9, 132.3, 131.5, 131.3, 130.7, 128.6, 127.9, 127.0, 126.8, 125.4, 125.3, 125.2,
124.8, 122.6, 33.1, 32.7, 23.0, 14.1. HRMS: Calculated for C18H19 [M+H]+ 235.1481; found 235.1478.
3i) 1-hexylanthracene Purified by FCC using pentane. Yield: 85% Molecular Formula: C20H22 1H NMR
(300 MHz, CDCl3) δ 8.62 (s, 1H), 8.44 (s, 1H), 8.12-7.94 (m, 2H), 7.89 (d, J = 8.4 Hz, 1H), 7.54- 7.44 (m,
2H), 7.44-7.36 (m, 1H), 7.36-7.29 (m, 1H), 3.22 (t, J = 9 Hz, 2H), 1.99-1.78 (m, 2H), 1.63-1.23 (m, 6H),
0.94 (t, J = 6.9 Hz, 3H). 13C NMR (75MHz, CDCl3) δ 138.8, 132.2, 131.5, 131.2, 130.6, 128.5, 127.9,
126.9, 126.7, 125.3, 125.2, 125.1, 124.7, 122.5, 33.3, 31.8, 30.4, 29.6, 22.7, 14.1. HRMS: Calculated
for C20H23 [M+H]+ 236.1794; found 236.1791.
3j) 1-isopropylanthracene Purified by FCC using pentane. Isolated as an 69:41 mixture with
anthracene Yield: 55% (79% as an 69:41 mixture with anthracene) Molecular Formula: C17H16 1H NMR
(300 MHz, CDCl3) δ 8.70 (s, 1H), 8.45 (s, 1H), 8.14-7.95 (m, 2H), 7.88 (d, J = 8.0 Hz, 1H), 7.59- 7.34 (m,
4H), 3.94 (hept, J = 6.9 Hz, 1H), 1.50 (d, J = 6.8 Hz, 6H). 24 13C NMR (75MHz, CDCl3) δ 144.54, 132.33,
131.49, 131.11, 130.03, 128.62, 127.79, 127.03, 126.58, 125.32, 125.20, 125.16, 122.05, 120.84,
28.77, 23.53. HRMS: Calculated for C16H17O [M+H]+ 221.1325; found 221.0956.
3k) 1-cyclopropylanthracene Purified by FCC using pentane. Yield: 66% Molecular Formula: C17H14 1H
NMR (300 MHz, CDCl3) δ 8.99 (s, 1H), 8.45 (s, 1H), 8.14- 8.08 (m, 1H), 8.06-7.99 (m, 1H), 7.89 (d, J =
8.5 Hz, 1H), 7.55-7.46 (m, 2H), 7.39 (dd, J = 8.5, 6.8 Hz, 1H), 7.32-7.21 (m, 1H), 2.62-2.36 (m, 1H),
1.20-1.13 (m, 2H), 0.89-0.81 (m, 2H). 13C NMR (75MHz, CDCl3) δ 139.3, 132.1, 132.1, 131.7, 131.5,
128.8, 128.1, 127.0, 126.9, 125.5, 125.4, 125.2, 123.2, 123.0, 13.7, 6.5.