Elaboration of a novel effective approach to enantiopure functionalised 2,2′-dialkyl-1,1′-binaphthyls by stereoconservative cross-couplings at positions 2 and 2′

Article abstract of DOI:10.1016/j.tetlet.2004.05.016

The yield and the stereochemical outcome of methylations of 1,1 ^′-binaphthyl-2,2^′-dielectrophiles (ditriflate and diiodide) clearly depend on the reactivity of the organometallics used. It was found that only the Negishi reaction of

Full text of DOI:10.1016/j.tetlet.2004.05.016

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 5279–5282
Elaboration of a novel effective approach to enantiopure
functionalised 2,20-dialkyl-1,10-binaphthyls by stereoconservative
q
cross-couplings at positions 2 and 20
*
ꢀ
Peter Kasak and Martin Putala
Department of Organic Chemistry, Faculty of Natural Sciences, Comenius University in Bratislava,
Mlynskꢀa dolina, 842 15 Bratislava, Slovak Republic
Received 14 January 2004; revised 26 April 2004; accepted 5 May 2004
Abstract—The yield and the stereochemical outcome of methylations of 1,10-binaphthyl-2,20-dielectrophiles (ditriflate and diiodide)
clearly depend on the reactivity of the organometallics used. It was found that only the Negishi reaction of a diiodide allows direct
effective synthesis of non-racemic functionalised C2-symmetric 2,20-dialkyl-1,10-binaphthyls.
Ó 2004 Elsevier Ltd. All rights reserved.
The unique stereochemical properties of axially chiral
2,20-substituted 1,10-binaphthyl derivatives are the rea-
son for the enhanced interest in their synthesis and
applications. As a result of this interest they have
become one of the most important groups of artificial
chiral-pool compounds. Many applications of 1,10-
binaphthyl derivatives have been found especially C2-
symmetric examples having heteroatom based groups in
positions 2 and 20 (N, P, As, O, S). Only a limited
number of applications of 1,10-binaphthyl derivatives
bearing carbon groups at positions 2 and 20 have been
reported1–7 and these derivatives almost exclusively have
C(sp3)-monocarbon groups at the above-mentioned
positions. However, their reported applications in ste-
reoselective synthesis (as chiral catalysts,1;2 ligands,3;4
reagents,5 additives6 and auxiliaries7) are promising. A
reason for their limited application is that their synthesis
in nonracemic form has not been properly investigated.
Their synthesis is most often based on the preparation of
the enantiopure 2,20-dimethyl derivative 1a or 1,10-
binaphthyl-2,20-dicarboxylic acid as key intermediates
followed by functionalisation. Enantiopure 1,10-
binaphthyl-2,20-dicarbonitrile8 or 2,20-bis(4-alkyloxazo-
lin-2-yl) derivatives6;9 can be used as alternative inter-
mediates.
Non-racemic 2,20-dimethyl-1,10-binaphthyl (1a) has been
prepared by stereoselective Grignard coupling from
1-bromo-2-methylnaphthalene.10 The former was also
obtained by a stereoselective Suzuki coupling.11 Cur-
rently, 1a is prepared exclusively by effective stereo-
conservative nickel catalysed methylation of easily
accessible enantiopure 2,20-ditriflate 2a with methyl-
magnesium halides, a method, which has been reported
independently by several research groups.1;3;12
The direct introduction of functionalised alkyl groups
would be of interest for the efficient synthesis of func-
tionalised derivatives. However, Grignard reagents are
intolerant of many functional groups under cross-cou-
pling reaction conditions (at the boiling point of the
solvent used), so functionalisation is only possible after
the cross-coupling reaction. Therefore we performed a
systematic study on the methylations of 1,10-binaphthyl-
2,20-dielectrophiles 2 (the ditriflate 2a and the diiodide
2b) via cross-coupling reactions with a variety of orga-
nometallic reagents. These reactions are also interesting
from a stereochemical point of view because they take
place at positions 2 and 20, where nonbonding interac-
tions between substituents play a crucial role in the
configurational stability of the 1,10-binaphthyl deriva-
tives and hence there is a risk of racemisation during the
Keywords: Aryl triflate; Aryl iodide; Binaphthyl; Cross-coupling;
Kumada; Negishi; Stereoconservative.
q Supplementary data associated with this article can be found, in the
online version, at doi:10.1016/j.tetlet.2004.05.016
* Corresponding author. Tel.: +421-2-60296-323; fax: +421-2-60296-
690; e-mail: putala@fns.uniba.sk
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.05.016

5280
P. Kasꢀak, M. Putala / Tetrahedron Letters 45 (2004) 5279–5282
reaction.13 1,10-Binaphthyl-2,20-dielectrophiles 2 should
be considered as moderately electron rich but highly
strained substrates (seeing that there is a bulky
1-naphthyl substituent adjacent to the site of the cross-
coupling reaction).
X
X
R-M
[Pd] or [Ni]
R
R
R
H
+
2
1
3
For methylations of binaphthyl dielectrophiles with
various organometallic reagents we examined a variety
of catalysts (Pd and Ni complexes with PPh3, P(2-
furyl)3, P(o-tolyl)3, dppe, dppp, dppf ligands), solvents
(Et2O, THF, dioxane, DME, NMP, toluene) and addi-
tives (K2CO3, K3PO4 and CsF for the Suzuki coupling,
LiCl for Stille coupling) analogous to the conditions for
effective methylations of aryl triflates and aryl iodides
described in literature. The best results under optimised
conditions are presented (Table 1, Scheme 1).
a: R = Me
b: R = Bn
c: R = Et
a: X = OTf
b: X = I
d: R = [CH2]2CO2Me
e: R = [CH2]2CN
Scheme 1. Alkylations of 1,10-binaphthyl-2,20-dielectrophiles 2.
binaphthyl derivatives were obtained from the Stille
reaction. The stereochemical result of the reaction was
found to be dramatically dependent on the reactivity of
the organometallic reagent used. Only two extreme
results were observed: either complete conservation (in
the case of Mg, Al and Zn; Table 1, entries 9–12) or
almost complete loss (racemisation in the case of B and
Sn; Table 1, entries 13–15) of configuration from the
substrate (diiodide 2b). Similar stereochemical results
were also observed in our study on the synthesis of 1,10-
binaphthyl-2,20-diyl bridged ferrocene by cross-coupling
reactions from the diiodide 2b.14 The different stereo-
chemical results are most probably caused by differences
in mechanistic pathways, which have been reported
elsewhere.14
Firstly, we examined methylations of the more easily
accessible ditriflate 2a. The reactivity of the organome-
tallic reagent was found to be crucial for the efficiency of
the reaction. The desired product 1a was obtained in
high yields only in the case of the most reactive
reagents––methylmagnesium halides and trimethyl-
aluminium (Table 1, entries 1–4). A good yield of 1a was
also obtained from the Negishi reaction, however, the
methylzinc reagent had tobe used in higher excess
(Table 1, entries 5 and 6), otherwise, the monomethyl-
ated derivative 3a was found to be the main product. In
all these cases, 1a was isolated in enantiopure form––
with complete conservation of configuration––from the
ditriflate 2a. The use of less reactive organometallics (B,
Sn) did not result in the formation of a detectable
amount of the desired product 1a.
The Negishi reaction of the diiodide 2b with alkylzinc
halides, the method with the highest potential for the
synthesis of homochiral functionalised 2,20-dialkylated
1,10-binaphthyls 1, was tested on a few examples (Table
2). It was found that the yields of the desired products 1
were slightly lower if the alkyl groups, which were
introduced contained hydrogen on the b-carbon atom
(Table 2, entries 2, 4 and 5). As a result of b-hydrogen
elimination, small amounts of monoalkylated, hydro-
In the case of the more reactive diiodide 2b (already
commercially available), the desired product 1a was
isolated from each type of cross-coupling reaction and
in excellent yields from the more reactive organometal-
lics. Alsotraces of partially stannylated and butylated
Table 1. Methylations of 1,10-binaphthyl-2,20-dielectrophiles 215
Entry
2
Equiv. of Me–Ma
Cat. (5 mol %)a
Solvent
Yield of 1ab (%)
Ee of 1ac (%)
13;12
21
3
(R)-2ad
(S)-2ad
(S)-2a
(S)-2a
(S)-2a
(S)-2a
(S)-2a
(S)-2a
(R)-2b
(R)-2b
(R)-2b
(R)-2b
(R)-2b
(R)-2b
(R)-2b
2 Me–MgBr
2 Me–MgI
2 Me–MgI
2 Me–AlMe2
2 Me–ZnI
NiCl2dppp
NiCl2(PPh3)2
NiCl2dppe
PdCl2dppf
Pd(PPh3)4
Pd(PPh3)4
[Pd]
Et2O
Et2O
Et2O
99
89
89
85
20
62
0
>98
>98
>98
>98
>98
>98
––
4
PhMe
THF
THF
5
6
3 Me–ZnI
2 (MeBO)3
e
7
Various
Various
Et2O
8
2 Me–SnR3(Me, Bu)f
2 Me–MgI
[Ni] or [Pd]
NiCl2dppe
PdCl2dppf
Pd(PPh3)4
NiCl2dppe
Pd(PPh3)4
Pd[P(2-furyl)3]4
Pd[P(2-furyl)3]4
0
––
9
90
87
92
93
65
70
56
>98
>98
>98
>98
5
10
11
12
13
14
15
2 Me–AlMe2
2 Me–ZnI
2 Me–ZnI
PhMe
THF
THF
e
2 (MeBO)3
2 Me–SnMe3
Dioxane–THF
THF
THF
f
0
f
2 Me–SnBu3
0
a With respect toAr–I or Ar–OTf.
b Isolated yield.
c Determined by HPLC on (+)-poly(triphenylmethyl) methacrylate/silica.
d Including 3,30-diarylated 2a.
e +3 equiv K2CO3 (with respect toAr–I or Ar–OTf).
f +3 equiv LiCl (with respect toAr–I or Ar–OTf).

P. Kasꢀak, M. Putala / Tetrahedron Letters 45 (2004) 5279–5282
Table 2. Alkylations of 1,10-binaphthyl-2,20-dielectrophiles 215
5281
Entry
2
Equiv of R–Ma
Cat. (5 mol %)a
Solvent
Yield of 1b (%)
Ee of 1 (%)
Yield of 3b (%)
1
2
3
4
5
(S)-2b
(S)-2b
(S)-2a
(R)-2b
(R)-2b
2 Bn–ZnBr
2 Et–ZnEt
Pd(dba)2, dppf (1:1)d
Pd(PPh3)4
THF
THF
THFe
THFe
THFe
1b, 85
1c, 60
1d, 0
>98c
n.d.f
––
>98c
>96g
3b, traces
3c, 20
3d, 0
3 MeO2CCH2CH2–ZnI
2 MeO2CCH2CH2–ZnI
2 NCCH2CH2–ZnI
[Ni] or [Pd]
Pd(PPh3)4
Pd(PPh3)4
1d, 68
1e, 62
3d, 12
3e, 21
a With respect toAr–I or Ar–OTf.
b Isolated yield.
c Determined with HPLC on (+)-poly(triphenylmethyl) methacrylate/silica (1b) or Chiralcel Daicel OD-RH column (1d).
d +3 equiv Bu4NI (with respect toAr–I).
e THF contains 0.2 mL of DMA and 1 mL of benzene originating from the synthesis of the zinc reagent. Reaction was performed at 40 °C.
f Not determined.
g Determined by comparison of the specific rotations of the diacid 1f (R ¼ CH2CH2CO2H) obtained by hydrolysis of 1d and 1e.
(f) Ooi, T.; Sugimoto, H.; Doda, K.; Maruoka, K.
Tetrahedron Lett. 2001, 42, 9245–9248; (g) Ooi, T.;
Takahashi, M.; Doda, K.; Maruoka, K. J. Am. Chem.
Soc. 2002, 124, 7640–7641; (h) Ooi, T.; Doda, K.;
Maruoka, K. J. Am. Chem. Soc. 2003, 125, 2054–2055;
(i) Ooi, T.; Miki, T.; Taniguchi, M.; Shiraishi, M.;
Takeuchi, M.; Maruoka, K. Angew. Chem., Int. Ed.
2003, 42, 3796–3798; (j) Maruoka, K.; Ooi, T. Chem.
Rev. 2003, 103, 3013–3028, and references cited therein;
(k) Ooi, T.; Kameda, M.; Maruoka, K. J. Am. Chem. Soc.
2003, 125, 5139–5151; (l) Ooi, T.; Doda, K.; Maruoka, K.
J. Am. Chem. Soc. 2003, 125, 9022–9023.
dehalogenated products 3 were obtained from the
reaction mixture in these cases. Nevertheless, the desired
products 1 were obtained in reasonable yields and very
efficiently with respect tothe number of required reac-
tion steps and moreover, in enantiopure form.
A control experiment with ditriflate 2a (Table 2, entry 3)
showed that alkylation with a more complex alkylzinc
halide does not give, in contrast to the methylation
under analogous conditions, even traces of the dialkyl-
ated product 1d.
3. Xiao, D.; Zhang, Z.; Zhang, X. Org. Lett. 1999, 1, 1679–
1682.
In conclusion, our study on the methylation of 1,10-
binaphthyl-2,20-dielectrophiles 2 showed that the Negi-
shi cross-coupling reaction of the more reactive diiodide
2b is the most convenient synthetic approach for the
effective direct synthesis of enantiopure 1,10-binaphthyl
derivatives bearing functionalised alkyl groups at posi-
tions 2 and 20. Monoalkylated hydro-dehalogenated
products 3 were isolated, besides the desired dialkylated
ones 1, if the alkyl groups introduced contained
hydrogen on the b-carbon atom. Our study on the
synthesis and applications of functionalised 2,20-dialkyl-
ated 1,10-binaphthyls is currently in progress.
4. (a) Tamao, K.; Yamamoto, H.; Matsumoto, H.; Miyake,
N.; Hayashi, T.; Kumada, M. Tetrahedron Lett. 1977, 18,
1389–1392; (b) Colletti, S. L.; Halterman, R. L. Tetra-
hedron Lett. 1992, 33, 1005–1008; (c) Halterman, R. L.;
Ramsey, T. H. Organometallics 1993, 12, 2879–2880; (d)
Halterman, R. L.; Ramsey, T. M.; Chen, Z. J. Org. Chem.
1994, 59, 2642–2644; (e) Shi, M.; Itoh, N.; Masaki, Y. J.
Chem. Res. (S) 1996, 352–363; (f) Uozomi, Y.; Kyota, H.;
Kishi, E.; Kityama, K.; Hayashi, T. Tetrahedron: Asym-
metry 1996, 7, 1603–1606; (g) Bourghida, M.; Widhalm,
M. Tetrahedron: Asymmetry 1998, 9, 1073–1083; (h)
Widhalm, M.; Mereiter, K.; Bourghida, M. Tetrahedron:
Asymmetry 1998, 9, 2983–2986; (i) Gleich, D.; Herrmann,
W. A. Organometallics 1999, 18, 4354–4361; (j) Lu, G.; Li,
X.; Zhou, Z.; Chan, W. L.; Chan, A. S. C. Tetrahedron:
Asymmetry 2001, 12, 2147–2152.
5. (a) Rychnovsky, S. D.; McLernon, T. L.; Rajapakse, H.
J. Org. Chem. 1996, 61, 1194–1195; (b) Nanni, D.; Curran,
D. P. Tetrahedron: Asymmetry 1996, 7, 2417–2422; (c)
Procter, D. J.; Rayner, C. M. Synth. Commun. 2000, 30,
2975–2987; (d) Dai, W.-M.; Wu, A.; Wu, H. Tetrahedron:
Asymmetry 2002, 13, 2187–2191.
6. Meyers, A. I.; Nguyen, T.; Stoianova, D.; Sreebama, N.;
Woody, R. W.; Koslowski, A.; Fleischhauer, J. Chirality
1997, 9, 431–434.
Acknowledgements
The authors are thankful to Professor Albrecht Mann-
schreck for HPLC analysis. This work was supported by
the Slovak Grant Agency for Science (grant No. 1/0091/
03) and Comenius University (grants No. UK/53/2001
and UK/149/2002).
7. (a) Colletti, S. L.; Halterman, R. L. Organometallics 1992,
11, 980–983; (b) Harris, J. M.; McDonald, R.; Vederas, J.
C. J. Chem. Soc., Perkin Trans. 1 1996, 2669–2674; (c)
Gaucher, A.; Bintein, F.; Wakselman, M.; Mazaleyrat,
J.-P. Tetrahedron Lett. 1998, 39, 575–578.
References and notes
1. Ooi, T.; Kameda, M.; Maruoka, K. J. Am. Chem. Soc.
1999, 121, 6519–6520.
ꢀ
2. (a) Johannsen, M.; Jørgensen, K. A.; Helmchen, G. J. Am.
Chem. Soc. 1998, 120, 7637–7638; (b) Olah, G. A.; Rasul,
G.; Prakash, G. K. S. J. Am. Chem. Soc. 1999, 121, 9615–
9617; (c) Iwasaki, F.; Maki, T.; Nakashima, W.; Ono-
mura, O.; Matsumura, Y. Org. Lett. 1999, 1, 969–972; (d)
Iwasaki, F.; Maki, T.; Onomura, O.; Nakashima, W.;
Matsumura, Y. J. Org. Chem. 2000, 65, 996–1002; (e) Ooi,
T.; Doda, K.; Maruoka, K. Org. Lett. 2001, 3, 1273–1276;
8. Kasak, P.; Putala, M. Collect. Czech. Chem. Commun.
2000, 65, 729–740.
9. For example see: Nelson, T. D.; Meyers, A. I. J. Org.
Chem. 1994, 59, 2655–2658.
10. Hayashi, T.; Hayashizaki, K.; Kiyoi, T.; Ito, Y. J. Am.
Chem. Soc. 1988, 110, 8153–8156.
ꢀ
11. Cammidge, A. N.; Crepy, K. V. L. Chem. Commun. 2000,
1723–1724.

5282
P. Kasꢀak, M. Putala / Tetrahedron Letters 45 (2004) 5279–5282
12. (a) Gingras, M.; Dubois, F. Tetrahedron Lett. 1999, 40,
1309–1312; (b) Clyne, D. S.; Jin, J.; Genest, E.; Gallucci,
J. C.; RajanBabu, T. V. Org. Lett. 2000, 2, 1125–1128.
13. Putala, M. Enantiomer 1999, 4, 243–262, and references
cited therein.
7.51 (d, 3J ¼ 8:5 Hz, 2H, Ar-H), 7.40 (ddd, J ¼ 1:1, 7.0
8.0 Hz, 2H, Ar-H), 7.21 (ddd, J ¼ 1:3, 7.0, 8.5 Hz, 2H, Ar-
H), 7.03 (d, 3J ¼ 8:5 Hz, 2H, Ar-H), 2.41–2.25 (m, 4H,
CH2), 1.02 (dd, 6H, CH3). 13C NMR (CDCl3, d): 135.78,
134.65, 133.49, 132.31, 128.26, 127.78, 127.11, 126.30,
ꢀ
ꢀꢁ
14. Kasak, P.; Miklas, M.; Putala, M. J. Organomet. Chem.
2001, 637–639, 318–326.
126.02, 125.42, 29.85, 15.56.
24
D
(R)-1d: White oil. ½aꢀ )9.8 (c 0.83, CHCl3). 1H NMR
15. General procedure: A solution of 2 mmol (if not given
otherwise) of organometallic reagent in about 2 mL of
solvent was added dropwise to a solution of 285 mg
(0.5 mmol) 2a or 253 mg (0.5 mmol) 2b, 0.05 mmol of
catalyst and additive in 5 mL of dried solvent and the
reaction mixture was heated to reflux (if not given
otherwise) overnight under a nitrogen atmosphere. After
cooling to 0 °C, the reaction mixture was poured into a
10% aqueous cooled solution of HCl. The organic layer
was washed twice with water and brine, dried over
anhydrous MgSO4 and the solvent was removed in vacuo.
The product was isolated by flash chromatography on
silica, using hexane or hexane–dichloromethane from 9:1
up to4:1 as eluents.
(CDCl3, d): 7.93 (d, 3J ¼ 8:5 Hz, 2H, Ar-H), 7.89 (d,
3J ¼ 8:1 Hz, 2H, Ar-H), 7.53 (d, J ¼ 8:5 Hz, 2H, Ar-H),
3
7.41 (ddd, J ¼ 1:2, 7.6, 8.3 Hz, 2H, Ar-H), 7.20 (ddd,
3
J ¼ 1:3, 7.3, 8.2 Hz, 2H, Ar-H), 6.98 (d, J ¼ 8:4 Hz, 2H,
Ar-H), 3.52 (s, 6H, OCH3), 2.25–2.80 (m, 8H, CH2). 13C
NMR (CDCl3, d): 173.41, 136.88, 134.66, 133.32, 132.62,
128.54, 128.18, 127.18, 126.50, 126.33, 125.66, 51.68,
34.71, 29.08. IR (CHCl3, cmꢁ1): 1705, 1230, 1005.
24
D
(R)-1e: Yellowish solid. Mp 83–86 °C. ½aꢀ )51.4 (c 1.01,
1
CHCl3). H NMR (CDCl3, d): 8.02 (d, 3J ¼ 8:6 Hz, 2H,
Ar-H), 7.88 (d, 3J ¼ 8:2 Hz, 2H, Ar-H), 7.51 (d,
3J ¼ 8:6 Hz, 2H, Ar-H), 7.40 (ddd, J ¼ 1:1, 7.0, 8.5 Hz,
2H, Ar-H), 7.19 (ddd, J ¼ 1:2, 6.9, 8.3 Hz, 2H, Ar-H), 6.96
(d, 3J ¼ 8:6 Hz, 2H, Ar-H), 2.80–2.60 (m, 4H, CH2) 2.33–
2.23 (m, 4H, CH2). 13C NMR (CDCl3, d): 134.39, 134.11,
132.92, 132.82, 129.17, 128.35, 127.01, 126.78, 126.25,
1
1b: White crystalline solid. H NMR (CDCl3, d): 7.86 (d,
3J ¼ 8:7 Hz, 4H, Ar-H), 7.38 (d, J ¼ 8:3 Hz, 2H, Ar-H),
3
7.35 (dd, J ¼ 2:1, 8.6 Hz, 2H, Ar-H) 7.17 (ddd, J ¼ 1:9,
5.6, 6.3 Hz, 2H, Ar-H), 7.15–7.08 (m, 8H, Ar-H), 6.82 (m,
4H, Ar-H), 3.62 (d, 2J ¼ 15:3 Hz, 2H, CH2), 3.45 (d,
2J ¼ 15:3 Hz, 2H, CH2). 13C NMR (CDCl3, d): 140.37,
137.84, 134.78, 133.01, 132.32, 129.30, 128.10, 127.88,
125.81, 118.97, 29.56, 17.75. IR (CHCl3, cmꢁ1): 2225.
24
D
(R)-1f: White solid. Mp 240–245 °C. ½aꢀ +38.5 (c 0.35,
1
CHCl3). H NMR (CDCl3, d): 7.92 (d, 3J ¼ 8:4 Hz, 2H,
Ar-H), 7.87 (d, 3J ¼ 8:0 Hz, 2H, Ar-H), 7.52 (d,
3J ¼ 8:4 Hz, 2H, Ar-H), 7.39 (ddd, J ¼ 1:2, 6.9, 8.3 Hz,
2H, Ar-H), 7.18 (ddd, J ¼ 1:4, 6.9, 8.2 Hz, 2H, Ar-H), 6.95
126.24, 126.15, 125.80, 125.35, 38.57. (S)-1b: Mp 172–
173 °C. ½aꢀ
19:5
D
3
+14.4 (c 1.0, CHCl3). (RS)-1b: Mp 114–
(d, J ¼ 8:4 Hz, 2H, Ar-H), 2.40–2.80 (m, 8H, CH2). 13C
116 °C.
NMR (CDCl3, d): 178.08, 134.83, 133.60, 131.83, 131.36,
127.34, 127.04, 125.38, 124.68, 124.64, 124.40, 32.17,
26.91.
1c: Colourless oil. 1H NMR (CDCl3, d): 7.88 (d,
3J ¼ 8:2 Hz, 2H, Ar-H), 7.87 (d, J ¼ 8:3 Hz, 2H, Ar-H),
3