Heterocoupling of 2-naphthols enabled by a copper-N-heterocyclic carbene complex

Article abstract of DOI:10.1039/c3cc38675a

The reactivity of a Cu catalyst for oxidative coupling is modulated by a small molecule additive, diethyl malonate, that slows over-oxidation of 2-naphthols. Efficient heterocoupling between electron-rich and electron-poor 2-naphthols/2-naphthylamines affords C₁-symmetric BINOLs with yields ranging from 35-98%.

Full text of DOI:10.1039/c3cc38675a

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Heterocoupling of 2-naphthols enabled by a
copper–N-heterocyclic carbene complex†
Cite this: Chem. Commun., 2013,
49, 1835
`
´ ´
Michael Holtz-Mulholland, Mylene de Leseleuc and Shawn K. Collins*
Received 3rd December 2012,
Accepted 17th January 2013
DOI: 10.1039/c3cc38675a
www.rsc.org/chemcomm
The reactivity of a Cu catalyst for oxidative coupling is modulated by a
small molecule additive, diethyl malonate, that slows over-oxidation
of 2-naphthols. Efficient heterocoupling between electron-rich and
electron-poor 2-naphthols/2-naphthylamines affords C1-symmetric
BINOLs with yields ranging from 35–98%.
A wide variety of structurally diverse, biologically active biaryls are
formed in Nature via the oxidative coupling of phenols and
naphthols. In an effort to mimic the efficacy of Nature, biomimetic
oxidative couplings have been developed using a variety of different
metal complexes derived from Cu, V, Ru, Fe and Mn.1,2 Copper–
amine complexes have attracted the most attention of the transition
Scheme 1 Heterocoupling of electronically differentiated 2-naphthols.
metals, due to their similarity to copper-containing oxidases.3 Sub- and only a 32% yield of the desired product 3a was obtained
sequently, these copper–amine complexes have been applied to the (Scheme 1). When more exotic heterocouplings were attempted
preparation of axially chiral natural products and chiral polymers, employing 2-naphthylamines or phosphonate containing
but perhaps the most common utility is the synthesis of enantiopure substrates, the formation of a soup of overoxidation products
binaphthyl type ligands.4 The axially chiral biaryl motif is considered was observed and no trace of the desired phosphonate 4a or the
a privileged scaffold in asymmetric catalysis.5 A variety of complexes NOBIN-like amine 5a could be isolated. Consequently, we
have been developed for the synthesis of C2-symmetric ligand envisioned developing a more versatile and general procedure
scaffolds,5 but much less attention has been given to the preparation for oxidative heterocoupling.9 Herein we report on the efficient
of C1-symmetric ligand structures.2 The lack of interest is surprising oxidative heterocoupling of 2-naphthols that overcomes the
given the utility of the C1-symmetric structures in asymmetric aforementioned limitations.
catalysis, materials science and supramolecular chemistry.5
Based upon our interest in NHC–Cu catalysts with the general
The oxidative coupling of electronically dissimilar 2-naphthols structure (NHC)CuX,10 we investigated these complexes as catalysts
is typically challenging (Scheme 1).6,7 In general, the limitations for heterocoupling. The investigations began by studying the
include: (1) the formation of homocoupling products and hence coupling of the methyl ester 2a with an excess (2 eq.) of 2-naphthol
the need for an excess of the electron-rich 2-naphthol coupling 1a (Table 1). Our investigations employed a previously reported
partner or the use of slow-addition techniques,8 (2) formation of oxidant system (Oxones, AgNO3, THF).11 The first two Cu-based
overoxidation products which hamper purification. In select cases, catalysts surveyed (Cu(IPr)Br and Cu(SIMes)Br) gave good yields of
the use of harsh oxidants such as Oxones and catalysts with the heterocoupling product 3a (63–67%) (entries 1 and 2). However
limited solubility are necessary.2 To demonstrate the difficulty the formation of over-oxidation products was observed.12
of oxidative heterocoupling, the popular CuCl–TMEDA catalyst
In an effort to develop a milder, more environmentally
system11 was employed for the oxidative coupling of 1a and 2a friendly oxidant system, the reduction of the loading of silver
additive and replacement of Oxones by molecular oxygen was
investigated. Based upon the ease of synthesis, Cu(SIMes)Br
´
´
Departement de Chimie, Centre for Green Chemistry and Catalysis, Universite de
was chosen as a catalyst for further optimization of the oxidant
system.13 When Oxones was replaced by an atmosphere of O2
(1 atm) and the loading of AgNO3 was reduced, the yield
increased to 77% (entry 5). Despite the increases in yield, the
´
´
´
Montreal, CP 6128 Station Downtown, Montreal, Quebec, Canada H3C 3J7.
E-mail: shawn.collins@umontreal.ca
† Electronic supplementary information (ESI) available: Experimental procedures
and characterisation data for all new compounds. See DOI: 10.1039/c3cc38675a
c
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Table 1 Optimization of the heterocoupling of 2-naphthols by Cu(NHC)X and
present, suggesting that DEM is needed to slow overoxidation of
the 2-naphthols rather than the resulting BINOL products.
Using the optimized reaction conditions, the synthesis of
C1-symmetric BINOLs was investigated (Table 2). Both electron-
rich and electron-poor 2-naphthols were studied (entries 2 and
3 respectively). The bromo-substituted BINOL derivative 3b was
isolated in excellent yield (95%) when using an excess of 7-bromo-
2-naphthol, and still afforded a good yield (58%) when both
starting materials were used in equimolar quantities. The
methoxy-BINOL 3c was formed efficiently via coupling even
when both naphthol starting materials were used in a 1 : 1 ratio
(75%). The oxidative coupling also proceeded smoothly when
substitution was included on the 2-naphthol ester, BINOLs 3d–f
were isolated in 46–98% yield depending on the ratio of
coupling partners materials used. The heterocoupling using
3-phenanthrol was problematic and low yields of 3g were obtained
(35–49%). Finally, the ester moiety could be substituted for
other groups: (1) a nitro-containing BINOL 3h was isolated in
discovery of small molecule additives
Entry 1a (# eq.) Catalyst
Additive (mol%); oxidanta Yieldb (%)
1
2
3
4
5
6
2
2
1
2
2
1
Cu(IPr)Br
None; oxone
63c
67c
8c
Cu(SIMes)Br None; oxone
Cu(SIMes)Br None; oxone
Cu(SIMes)Br None; O2
Cu(SIMes)Br DEM (50); O2
Cu(SIMes)Br DEM (10); O2
77c
98
79
a
c
b
Oxone = 1.1 eq., O2 = 1 atm. Isolated yields after chromatography.
AgNO3 = 100 mol%. DEM = diethyl malonate.
formation of highly coloured byproducts was still observed, indicat-
ing overoxidation was still occurring. Recently, Kozlowski, Stahl
and co-workers reported that small molecule over-oxidation pro-
ducts formed in the oxidative homocoupling of ester 2a could in
fact be acting as a ligand for the copper catalyst, controlling its
reactivity.14 Given the structural similarity of the proposed over-
oxidation products with common 1,3-dicarbonyl compounds, we
investigated adding diethyl malonate (DEM) to the reaction mixture
to modulate the reactivity of the copper–NHC catalyst (Table 1,
entries 5 and 6).15 When DEM (50 mol%) was added to the
oxidative coupling of 1a and 2a, the isolated yield increased from
77% to nearly quantitative (98%). Upon further optimization it was
found that by adding only 10 mol% of DEM, the heterocoupling of
a 1 : 1 mixture of 1a and 2a could proceed in 79% yield without the
need for any slow addition techniques.16 Other 1,3-dicarbonyl
compounds were equally or less effective than DEM.17
In an effort to discern the role played by DEM, the isolated
yield of the product ester 3a was examined with respect to the
quantity of DEM added (Fig. 1). The yield of the coupling product
remained relatively high regardless of whether 10 or 100 mol% of
DEM was used. The small amount of DEM needed implies that it
may be acting as a ligand and reactivity modulator for the Cu
catalyst.18 Secondly, we investigated whether the DEM could be
slowing over-oxidation of the ester 3a. Thus 3a was resubmitted
to the coupling conditions with various amounts of DEM and
was re-isolated after the designated reaction time. The amount of
re-isolated 3a remained constant regardless of whether DEM is
Table 2 Synthesis of C1-symmetric BINOLs via oxidative coupling
Product
Entry
(X eq.)
Yielda (%)
2
1
2
1
2
1
98b
79c
95b
58b
86b
75b
86b
72b
82
1
2
3a
3b
3
3c
2
1
1.5
1
2
3d
3e
46
98
4
3f
1
60
1
1.3
35b
49
5
3g
6
7
3h
3i
1
71b
62
1.3
8
4a
4b
4c
1
1
1
77c
50
62
9
10
11
5a
1
1.3
47
67
a
b
c
Fig. 1 Effect of DEM on the yield and stability of 3a under the optimized
Isolated yields following chromatography. DEM = 50 mol%. Some
reaction conditions.
compounds were prepared on 1 mmol scale: 3a = 77%, 4a = 66%.
c
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(d) L. Que, Jr. and W. B. Tolman, Angew. Chem., Int. Ed., 2002, 41,
1114–1137.
71% when equimolar quantities of starting materials were employed
(entry 6), and (2) a bromo-substituted BINOL 3i was isolated in 62%
when a slight excess of 2-naphthol was used.
4 (a) X. Li, J. Yang and M. C. Kozlowski, Org. Lett., 2001, 3, 1137–1140;
(b) M. Smrcina, J. Polakova, S. Vyskocil and P. Kocovsky, J. Org. Chem.,
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M. C. Kozlowski, J. Org. Chem., 2003, 68, 5500–5511. For examples of
polymer synthesis see: ( f ) X. Xie, P. W. Phuan and M. C. Kozlowski,
Angew. Chem., Int. Ed., 2003, 42, 2168–2170. For examples in natural
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6 A. Grandbois, M.-E. Mayer, M. Bedard, S. K. Collins and T. Michel,
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Y. Sugiyama and P. Yan, Tetrahedron Lett., 2007, 48, 8595–8598.
8 For an example of the state of the art in heterocoupling see:
H. Egami, K. Matsumoto, T. Oguma, T. Kunisu and T. Katsuki,
J. Am. Chem. Soc., 2010, 132, 13633–13635.
9 Electronics are key factors for successful heterocoupling, see:
(a) M. Smrcina, S. Vyskocil, B. Maca, M. Polasek, T. A. Claxton,
A. P. Abbott and P. Kocovsky, J. Org. Chem., 1994, 59, 2156–2163;
(b) K. Ding, Q. Xu, Y. Wang, J. Liu, Z. Yu, B. Du, Y. Wu, H. Koshima
and T. Matsuura, Chem. Commun., 1997, 693–694.
10 For reviews see: (a) S. Diez-Gonzalez and S. P. Nolan, Aldrichimica
Acta, 2008, 41, 43–51; (b) S. Gaillard, C. S. J. Cazin and S. P. Nolan,
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The investigation of the substrate scope continued by examining
the heterocoupling of 2-naphthols containing a phosphonate at the
3-position (Table 2). BINOL products containing phosphonates in
the 3 and/or 30-positions have found use in asymmetric catalysis,19
but the synthesis of these ligands via oxidative coupling is limited
to a single report involving homocoupling.3b The heterocoupling
of a phosphonate with an equimolar quantity of 2-naphthol
afforded the desired heterocoupling product 4a in 77% yield.
The heterocoupling afforded similar yields of the C1-symmetric
products when employing more electron-poor 2-naphthols (50%
of 4b) or electron-rich 2-naphthols (62% of 4c) (entries 9 and 10).
The extension of the substrate scope of the oxidative protocol
was expanded to include NOBIN derived ligands, which have
attracted increased attention in asymmetric catalysis.20 As a
consequence the number of methods for NOBIN synthesis has
expanded.21 The preliminary results involved the heterocoupling
of 2-naphthylamine with ester 2a using the optimized protocol
(entry 11). When using a slight excess of the 2-naphthylamine,
the desired NOBIN 5a was isolated in 67% yield.
In summary, a mild, efficient, catalytic heterocoupling of
2-naphthols has been developed using the mono-NHC Cu catalyst
Cu(SIMes)Br and an environmentally benign oxidant (O2). Of note
is the use of DEM as a small molecule additive that appears to
slow the formation of over-oxidation by-products, eliminating the
need for large excesses of one coupling partner. The protocol
afforded good yields of C1-symmetric BINOLs and the NOBIN 5a
(35–98%) and the first reported heterocoupling of phosphonate-
containing BINOLs 4a–c.
11 The references in which Cu(II) and Ag(I) were used in combination
see ref. 4a, 4b and M. Noji, M. Nakajima and K. Koga, Tetrahedron
Lett., 1994, 35, 7983–7984.
12 Highly coloured by-products are visible by TLC analysis.
13 S. Diez-Gonzalez, A. Correa, L. Cavallo and S. P. Nolan, Chem.–Eur. J.,
2006, 12, 7558–7564.
14 J. B. Hewgley, S. S. Stahl and M. C. Kozlowski, J. Am. Chem. Soc.,
2008, 130, 12232–12233.
15 The addition of naphthol additives to other catalytic oxidative
processes has been reported: T. Kunisu, T. Oguma and T. Katsuki,
J. Am. Chem. Soc., 2011, 133, 12937–12939.
This work was financially supported by the Natural Sciences
16 Quantities of starting materials and unreacted DEM can be recovered
after the reaction. AgNO3 is believed to abstract a halogen from
Cu(NHC)X (no reaction is observed without the Ag additive).
17 See ESI† for details.
´
and Engineering Research Council of Canada (NSERC), Universite
de Montreal and the Centre for Green Chemistry and Catalysis.
18 For an example of a Cu-catalyzed process modulated by malonates
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ˇ´
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`
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c
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