10.1002/chem.201800011
Chemistry - A European Journal
Ph
Angew. Chem. 2016, 128, 58–106; Angew. Chem. Int. Ed. 2016, 55,
58–102.
ClMgN(o-tolyl)2
O
2f: ClMgNAr2
Ph
2
(3 equiv)
[7]
Aryl–nitrogen bond forming products are known to be obtained from
aryl halides with no aid of transition metal catalysis. Through SNAr
mechanism, see a) R. Cano, D. J. Ramón, M. Yus, J. Org. Chem. 2011,
76, 654–660; b) D. Dehe, I. Munstein, A. Reis, W. R. Thiel, J. Org.
Chem. 2011, 76, 1151–1154; c) A. Kaga, H. Hayashi, H. Hakamata,
M. Oi, M. Uchiyama, R. Takita, S. Chiba, Angew. Chem. 2017, 129,
11969–11973; Angew. Chem. Int. Ed. 2017, 56, 11807–11811.
Through aryne intermediates, see: d) J. L. Bolliger, C. M. Frech,
Tetrahedron 2009, 65, 1180–1187; e) Y. Fang, Y. Zheng, Z. Wang,
Eur. J. Org. Chem. 2012, 1495–1498.
2-Me-THF is reported to be much less susceptible to the ring-opening
attack by benzylmagnesium chloride than THF. S. H. Christensen, T.
Holm, R. Madsen, Tetrahedron 2014, 70, 4942–4946.
We used a THF solution of ethylmagnesium chloride that was
purchased from Aldrich Co. On changing the solvent from THF to 2-
Me-THF, we changed the alkyl moiety of the alkylmagnesium
chloride from ethyl to butyl as butyl chloride is much more convenient
as a starting material of the Grignard reagent than ethyl chloride,
which has a low boiling point (12.3 °C).
N(o-tolyl)2
3kf: Ar1–NAr2 (60% yield)
2
H+
+
Ph
Ph
mesitylene
185 °C
72 h
HO
O
Ph
Ph
N(o-tolyl)2
4 (3% yield)
I
1k: Ar1–I
5 (3% yield)
I
2f
1k
H+
Ar1–NAr2
2
• –
Ph
Ph
• +
]
[ClMgNAr2
–O
2
I
Ph
[8]
[9]
1k
[Ar1–NAr2
NAr2
VI
2
[Ar1–I]• –
• –
]
2
III
– H+
I
II
MgClI
2f
Ph
•
Ph
•
Ph
IV
V
Scheme 2. A proof of the involvement of anion radical intermediates.
[10] A similar difference between alkali metal and alkaline earth metal is
observed also in the electron-catalyzed cross-coupling reaction of aryl
halides with organometallic reagents. As we mentioned in the
introductory section, no free aryl radicals are involved in the reaction
of arylmagnesium bromides. In contrast, the products derived from
aryl radical intermediates were observed in the reaction of aryllitiums.
For example, the reaction of phenyllithium, prepared from
bromobenzene (1.5 equiv) and tert-butyllithium (3.0 equiv), with 4-
iodoanisole (1l) in the presence of THF (6 equiv) in toluene at 110 °C
for 24 h gave 4-methoxybiphenyl only in 3% yield with a full
conversion of 1l, where anisole (60%) and 1,2-diphenylethane (39%)
were the main products. These are likely to be produced through a
hydrogen abstraction of 4-methoxyphenyl radical from toluene and
radical–radical homocoupling of the resulting benzyl radical. For the
detail of the reaction of phenyllithium with 1l, see Supporting
Information.
In conclusion, we have developed the electron-catalyzed
coupling reaction of magnesium diarylamides with aryl iodides to
give triarylamines, proceeding through single electron transfer
mechanism with no aid of transition metal catalysis.
Received: ((will be filled in by the editorial staff))
Published online on ((will be filled in by the editorial staff))
Keywords: triarylamines · anion radicals · C–N coupling · single-
electron-transfer
[1]
[2]
For recent reviews of the transition metal-catalyzed amination of aryl
halides, see: a) P. Ruiz-Castillo, S. L. Buchwald, Chem. Rev. 2016,
116, 12564–12649; b) I. P. Beletskaya, A. V. Cheprakov,
Organometallics 2012, 31, 7753–7808.
For the transition metal-catalyzed coupling reactions of aryl halides
with magnesium diarylamides, see: a) C. Chen, L.-M. Yang, Org. Lett.
2005, 7, 2209–2211; b) T. Hatakeyama, R. Imayoshi, Y. Yoshimoto, S.
K. Ghorai, M. Jin, H. Takaya, K. Norisuye, Y. Sohrin, M. Nakamura,
J. Am. Chem. Soc. 2012, 134, 20262–20265; c) X.-L. Li, W. Wu, X.-H.
Fan, L.-M. Yang, Org. Biomol. Chem. 2014, 12, 1232–1236.
[11] The possibility that the reaction proceeds through aryne intermediates
is excluded by the regiospecific production of triarylamines from all
the aryl iodides used here.
[12] There is some possibility that SET from a magnesium amide to an aryl
iodide takes place in an indirect manner, e.g., through an aryne
intermediate, generated upon deprotonation from the aryl iodide by
the magnesium amide, and the successive generation of an efficient
single electron donor as reported by Tuttle, Murphy and coworkers: J.
P. Barham, G. Coulthard, K. J. Emery, E. Doni, F. Cumine, G. Nocera,
M. P. John, L. E. A. Berlouis, T. McGuire, T. Tuttle, J. A. Murphy, J.
Am. Chem. Soc. 2016, 138, 7402–7410. For more discussion on
whether SET from a base to an aryl halide takes place directly or
indirectly, see the above and references cited therein.
[13] Anion radicals of alkyl aryl ethers are known to be converted into the
corresponding phenolate and the alkyl radical. a) U. Azzena, T.
Denurra, G. Melloni, J. Org. Chem. 1992, 57, 1444–1448; b) U.
Azzena, F. Dessanti, G. Melloni, L. Pisano, ARKIVOC 2002, (v), 181–
188. The fragmentation of this type is also studied in the
photostimulated SRN1 reaction of RS– (R = alkyl) with Ar–X, where
the anion radical [RSAr] • – decompose to R• and –SAr. c) R. A. Rossi,
S. M. Palacios, J. Org. Chem. 1981, 46, 5300–5304.
[3]
For reviews of SRN1 reaction, see: a) J. F. Bunnett, Acc. Chem. Res.
1978, 11, 413–420; b) R. A. Rossi, A. B. Pierini, A. B. Peñéñory,
Chem. Rev. 2003, 103, 71–167.
[4]
[5]
J. K. Kim, J. F. Bunnett, J. Am. Chem. Soc. 1970, 92, 7464–7466.
For the coupling of aryl Grignard reagents: a) E. Shirakawa, Y.
Hayashi, K. Itoh, R. Watabe, N. Uchiyama, W. Konagaya, S. Masui, T.
Hayashi, Angew. Chem. 2012, 124, 222–225; Angew. Chem. Int. Ed.
2012, 51, 218–221; b) E. Shirakawa, K. Okura, N. Uchiyama, T.
Murakami, T. Hayashi, Chem. Lett. 2014, 43, 922–924. For a
mechanistic study on the coupling of aryl Grignard reagents: c) N.
Uchiyama, E. Shirakawa, T. Hayashi, Chem. Commun. 2013, 49, 364–
366. For the coupling of arylzinc reagents: d) H. Minami, X. Wang, C.
Wang, M. Uchiyama, Eur. J. Org. Chem. 2013, 7891–7894; e) E.
Shirakawa, F. Tamakuni, E. Kusano, N. Uchiyama, W. Konagaya, R.
Watabe, T. Hayashi, Angew. Chem. 2014, 126, 531–535; Angew.
Chem. Int. Ed. 2014, 53, 521–525. For the coupling of arylaluminum
reagents: f) H. Minami, T. Saito, C. Wang, M. Uchiyama, Angew.
Chem. 2015, 127, 4748–4751; Angew. Chem. Int. Ed. 2015, 54, 4665–
4668. For the coupling of alkylzinc reagents: g) K. Okura, E.
Shirakawa, Eur. J. Org. Chem. 2016, 3043–3046. For the coupling of
tetraarylstannanes: h) Q. He, L. Wang, Y. Liang, Z. Zhang, S. F.
Wnuk, J. Org. Chem. 2016, 81, 9422–9427. For the coupling of
alkynylzinc reagents: i) K. Okura, H. Kawashima, F. Tamakuni, N.
Nishida, E. Shirakawa, Chem. Commun. 2016, 52, 14019–14022.
[14] The cyclization rate of 6,6-diphenyl-5-hexenoxy radical at 20 ºC is
estimated as kc = 5.0 × 107 s-1. C. Ha, J. H. Horner, M. Newcomb, T. R.
Varick, J. Org. Chem. 1993, 58, 1194–1198.
[15] The involvement of anion radical intermediates was supported also by
the following experiment. The reaction of 1,4-diiodobenzene (1h)
with magnesium diphenylamide (6 equiv) in mesitylene at 200 °C in a
short reaction period (4 h instead of 72 h as in entry 13 of Table 2)
gave the bisaminated product (3ha) and the monoaminated product
(3’ha) in 31% and 26% yields, respectively, with 64% conversion of
1h. Predominated production of 3ha even in the presence of a
considerable amount of the remaining 1h is rationally understood as
follows. An anion radical of 3’ha, generated upon the C–N bond
formation in the propagation step, undergoes another C–N bond
formation to be converted to an anion radical of 3ha leading to 3ha,
[6] For stimulating reviews on "electron catalysis", see: a) A. Studer, D. P.
Curran, Nat. Chem. 2014, 6, 765–773; b) A. Studer, D. P. Curran,
3
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