Acid-catalyzed [3,3] sigmatropic rearrangement of N-Cbz-diaryl hydrazide for the synthesis of mono-N-Cbz-1,1′-biaryl-2,2′-diamine

Article abstract of DOI:10.1002/ejoc.201001461

N-Cbz-Diaryl hydrazides undergo acid-catalyzed [3,3] sigmatropic rearrangement to afford N-Cbz-1,1′-biaryl-2,2′-diamines. The resultant products can be versatile synthetic platforms for a wide variety of C₂- and/or nonsymmetric axially chiral ligands and organocatalysts. N-Cbz-Diaryl hydrazides bearing either a neutral or electron-donating group underwent highly efficient acid-catalyzed [3,3] sigmatropic rearrangement to afford N-Cbz-1,1′-biaryl-2,2′-diamines. The resultant products allow elaboration of various new C₂- and/or nonsymmetric axially chiral ligands or organocatalysts.

Full text of DOI:10.1002/ejoc.201001461

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201001461
Acid-Catalyzed [3,3] Sigmatropic Rearrangement of N-Cbz-Diaryl Hydrazide
for the Synthesis of Mono-N-Cbz-1,1Ј-biaryl-2,2Ј-diamine
Sung-Eun Suh,[a] In-Keol Park,[a] Byeong-Yun Lim,[a] and Cheon-Gyu Cho*[a]
Keywords: Sigmatropic rearrangement / Hydrazides / Cross-coupling / Biaryls / Amines
N-Cbz-Diaryl hydrazides undergo acid-catalyzed [3,3] sig-
matropic rearrangement to afford N-Cbz-1,1Ј-biaryl-2,2Ј-di-
amines. The resultant products can be versatile synthetic
platforms for a wide variety of C2- and/or nonsymmetric axi-
ally chiral ligands and organocatalysts.
2,2Ј-diamino-1,1Ј-biaryl 4 (Scheme 2, Equation 1). More-
over, starting diaryl hydrazide 3 is readily accessed from
aryl hydrazide 1 through a Pd0- or CuI-catalyzed coupling
reaction with aryl halide 2.[7] Also disclosed was that aryl
hydrazide 5 can undergo a Fischer indolization reaction to
give N-Cbz-indole 7 with the N-carbamate group remaining
intact (Cbz in this case; Scheme 2, Equation 2).[8] We have
envisaged that the combination of these two results
(Scheme 2, Equations 1 and 2) would allow the synthesis of
1,1Ј-biaryl-2,2Ј-diamines 9 with one N-Cbz protecting
group. They would be valuable synthetic intermediates that
could provide not only C2-symmetric but also nonsymmet-
ric axially chiral scaffolds bearing one or two amino groups
(Scheme 2, Equation 3).[9]
Introduction
Axially chiral biaryls are important structural motifs as
versatile auxiliaries for various asymmetric synthetic trans-
formations.[1] Their biaryl cores are primarily prepared
through the CuII, FeIII, MnIII, or VIV/O2-mediated oxidat-
ive couplings of the corresponding aryl alcohols.[2] The re-
sultant 1,1Ј-biaryl-2,2Ј-diols then serve as platforms for
other biaryl ligands that include the famous 2,2Ј-bis(di-
phenylphosphanyl)-1,1Ј-binaphthyl (BINAP). Nitrogen an-
alogues, for example, 1,1Ј-binaphthyl-2,2Ј-diamine (BI-
NAM), have not been much explored until recently as chiral
ligands and chiral organocatalysts.[3] However, the lack of
general synthetic methods hampers their exploitation up to
their full potential. Unlike the BINOL system, an oxidative
coupling approach is not effective and gives only limited
success (Scheme 1, path A).[4] An acid-catalyzed rearrange-
ment reaction of diaryl hydrazine may provide a quick solu-
tion (Scheme 1, path B).[5] Unfortunately, the poor accessi-
bility of the starting diaryl hydrazines imposes severe limita-
tions.[6]
Scheme 1. Synthetic approaches to BINAM.
We have previously shown that diaryl hydrazide 3 is an
effective surrogate of diaryl hydrazine, effecting the acid-
catalyzed [3,3] sigmatropic rearrangement reaction to afford
[a] Department of Chemistry and Research Institute for Natural
Sciences, Hanyang University,
Seoul 133-791, South Korea
Fax: +82-2-2299-0762
E-mail: ccho@hanyang.ac.kr
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001461.
Scheme 2. Previous work on aryl hydrazides.
Eur. J. Org. Chem. 2011, 455–457
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
455

S.-E. Suh, I.-K. Park, B.-Y. Lim, C.-G. Cho
SHORT COMMUNICATION
Table 2. [3,3] Sigmatropic rearrangement of various diaryl hydraz-
ides.
Results and Discussion
Toward this goal, dinaphthalenyl hydrazide 8a was pre-
pared and studied for the [3,3] sigmatropic rearrangement
reaction under various acidic conditions (Table 1). In these
experiments, the reactions were carried out in a dilute acid
solution (a premixed 0.4 m acid solution in the correspond-
ing solvent). When heated in EtOH containing a strong
acid, the reaction was complete within a minute, affording
N-Cbz-BINAM 9a together with carbazole byproduct
10a[5b,7e] in essentially quantitative total yield (Table 1, En-
tries 1–3). The reactions with TFA or a weak acid took a
longer time (Table 1, Entries 4, 5, and 7). In the absence of
acid, less than 10% conversion was observed even after
heating at reflux overnight (Table 1, Entry 6). The reaction
can be carried out at ambient temperature (Table 1, En-
tries 8 and 9).
Table 1. [3,3] Sigmatropic rearrangement of 8a.
ous other C1-symmetric BINAM-type ligands and/or or-
ganocatalysts.
In order to address the possible effect of the N-Cbz posi-
tion, diaryl hydrazides 11a–11c containing a Cbz group at
the other nitrogen atom (i.e., 11a–11c; Table 3) were also
prepared. However, they gave similar results to their coun-
terparts (i.e., 8b, 8d, and 8k; Table 2).
Table 3. [3,3] Sigmatropic rearrangement of 11.
[a] Major component is BINAM (not 9a).
With this initial success in hand, we proceeded to probe
the scope and limitations of the reaction (Table 2).
As demonstrated, electron rich and neutral aryl hydraz-
ides 8b–8h and 8l rapidly underwent rearrangement reac-
tions to afford the corresponding N-Cbz-1,1Ј-biaryl-2,2Ј-di-
amines in good yield (Table 2, Entries 1–7 and 11). In these
cases, sulfuric acid gave better results than HCl. However,
those bearing an electron-withdrawing group at either the
para or meta position rearranged at a much slower rate with
poorer product yields (Table 2, Entries 9–11).[10] The diaryl
hydrazides with a meta substituent furnished a mixture of
two regioisomers (Table 2, Entries 4 and 11; 3:1 ratio in
both cases). Unlike bisnaphthalenyl hydrazides 8a and 8m,
no carbazole byproducts were noticed from the reactions of
the hydrazides bearing one naphthalene unit. Notable is
that 6-bromo-N-Cbz-binaphthyl diamine 9m was obtained
[a] A mixture of two regioisomers.
Conclusions
In summary, diaryl hydrazides bearing an acid-stable N-
from hydrazide 8m. It can be readily manipulated into vari- Cbz group effected the acid-catalyzed [3,3] sigmatropic re-
456
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 455–457

Synthesis of Mono-N-Cbz-1,1Ј-biaryl-2,2Ј-diamine
5500; c) S.-W. Hon, C.-H. Li, J.-H. Kuo, N. B. Barhate, Y.-H.
Liu, Y. Wang, C.-T. Chen, Org. Lett. 2001, 3, 869; d) M. Naka-
jima, I. Miyoshi, K. Kanayama, S. Hashimoto, M. Noji, K.
Koga, J. Org. Chem. 1999, 64, 2264; e) K. Ding, Q. Xu, Y.
Wang, J. Liu, Z. Yu, B. Du, Y. Wu, H. Koshima, T. Matsuura,
Chem. Commun. 1997, 693.
arrangement reaction to afford mono-N-Cbz-1,1Ј-biaryl-
2,2Ј-diamines. The resultant products allow elaboration of
a wide variety of C2- and nonsymmetric axially chiral li-
gands and organocatalysts.
[3] a) G.-N. Ma, S.-H. Cao, M. Shi, Tetrahedron: Asymmetry 2009,
20, 1086; b) T. Kano, Y. Tanaka, K. Osawa, T. Yurino, K.
Maruoka, Chem. Commun. 2009, 1956; c) S. Guizzetti, M. Be-
naglia, G. Celentano, Eur. J. Org. Chem. 2009, 3683; d) Y.-Q.
Jiang, Y.-L. Shi, M. Shi, J. Am. Chem. Soc. 2008, 130, 7202; e)
T. Kano, Y. Tanaka, K. Osawa, T. Yurino, K. Maruoka, J. Org.
Chem. 2008, 73, 7387; f) T. Zhang, S. Liu, M. Shi, M. Zhao,
Synthesis 2008, 17, 2819; g) Y. Zhao, Y. Wang, H. Sun, L. Li,
H. Zhang, Chem. Commun. 2007, 3186; h) H. Huang, T.
Okuno, K. Tsuda, M. Yoshimura, M. Kitamura, J. Am. Chem.
Soc. 2006, 128, 8719; i) A. Sakakura, K. Suzuki, K. Ishihara,
Adv. Synth. Catal. 2006, 348, 2457; j) J. Wang, H. Li, W. Duan,
L. Zu, W. Wang, Org. Lett. 2005, 7, 4713.
Experimental Section
Representative Procedure for the Preparation of N-Cbz-diaryl Hy-
drazides 8a–8m: A sealed tube was charged with 2-bromonaphthal-
ene (0.41 g, 2.0 mmol), benzyl 1-phenylhydrazinecarboxylate (5a;
0.58 g, 2.4 mmol), Pd(OAc)2 (0.02 g, 0.1 mmol), P(tBu)3·HBF4
(0.03 g, 0.1 mmol), Cs2CO3 (0.91 g, 2.8 mmol), and DMF (2 mL)
at room temperature. The reaction mixture was degassed, charged
with Ar, and heated to 100 °C. After 5 h, the reaction mixture was
concentrated and purified by column chromatography (hexane/
ethyl acetate = 8:1) to afford 8a (0.48 g, 65% yield) as a solid.
ˇ
[4]
S. Vyskocˇil, M. Smrcˇina, M. Lorenc, I. Tisˇlerová, R. D.
Representative Procedure for the Preparation of N-Cbz-1,1Ј-biaryl-
2,2Ј-diamines 9a–9m: To a sealed tube charged with 8a (50 mg,
0.14 mmol) in EtOH (1 mL) was added a drop of conc. H2SO4
(≈30 mg) at room temperature. After 5 min at 80 °C, the reaction
mixture was cooled to room temperature, concentrated, and puri-
fied by column chromatography (hexane/ethyl acetate = 8:1) to af-
ford 9a (36 mg, 73%) as an oil.
Brooks, J. J. Kulagowski, V. Langer, L. J. Farrugia, P. Ko-
cˇovský, J. Org. Chem. 2001, 66, 1359.
a) H. J. Shine, L. Kupczyk-Subotkowska, W. Subotkowski, J.
Am. Chem. Soc. 1985, 107, 6674; b) H. J. Shine, E. Gruszecka,
W. Subotkowski, M. Brownawell, J. San Filippo Jr., J. Am.
Chem. Soc. 1985, 107, 3218.
[5]
[6]
The first Pd-catalyzed coupling reaction of hydrazine (en route
to aryl hydrazine) has been recently reported. R. J. Lundgren,
M. Stradiotto, Angew. Chem. Int. Ed. 2010, 49, 2.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures and characterization data of all new
[7] a) W.-J. Lee, H.-Y. Kim, C.-G. Cho, Org. Lett. 2007, 9, 3185;
b) H.-Y. Kim, W.-J. Lee, H.-M. Kang, C.-G. Cho, Bull. Korean
Chem. Soc. 2007, 28, 1821; c) H.-M. Kang, H.-Y. Kim, J.-W.
Jung, C.-G. Cho, J. Org. Chem. 2007, 72, 679; d) H.-M. Kang,
Y.-K. Lim, I.-J. Shin, H.-Y. Kim, C.-G. Cho, Org. Lett. 2006,
8, 2047; e) Y.-K. Lim, J.-W. Jung, H. Lee, C.-G. Cho, J. Org.
Chem. 2004, 69, 5778; f) Y.-K. Lim, S. Choi, K. B. Park, C.-G.
Cho, J. Org. Chem. 2004, 69, 2603; g) K.-S. Lee, K.-Y. Kim, J.-
T. Shin, C.-G. Cho, Tetrahedron Lett. 2004, 45, 117; h) Y.-K.
Lim, S.-J. Pang, S.-U. Paek, H. Lee, C.-G. Cho, Bull. Korean
Chem. Soc. 2003, 24, 543; i) Y.-K. Lim, K.-S. Lee, C.-G. Cho,
Org. Lett. 2003, 5, 979; j) G.-S. Lee, Y.-K. Lim, C.-G. Cho,
Tetrahedron Lett. 2002, 43, 7463.
[8] a) I.-K. Park, S.-E. Suh, B.-Y. Lim, C.-G. Cho, Org. Lett. 2009,
11, 5454; b) Y.-K. Lim, C.-G. Cho, Tetrahedron Lett. 2004, 45,
1857.
[9] M. Yoshimura, T. Muraoka, H. Nakatsuka, H. Huang, M. Ki-
tamura, J. Org. Chem. 2010, 75, 4315.
[10] The Fischer indolization reactions of electron-deficient aryl hy-
drazines are often less efficient than those of electron-rich aryl
hydrazines: a) M. Jeanty, J. Blu, F. Suzenet, G. Guillaumet,
Org. Lett. 2009, 11, 5142; b) D. L. Hughes, Org. Prep. Proc.
Int. 1993, 25, 607; c) H. Ishii, Acc. Chem. Res. 1981, 14, 275.
Received: October 28, 2010
compounds including copies of their H and 13C NMR spectra.
1
Acknowledgments
Financial support was provided by grants from the National Re-
search Foundation (KRF-2008-313-C00467 and 2009-0080752). S.-
E. S., I.-K. P., and B.-Y. L. thank the BK21 Program. I.-K. P. is
thankful for a Seoul Fellowship.
[1] For recent reviews on biaryls, see: a) M. C. Kozlowski, B. J.
Morgan, E. C. Linton, Chem. Soc. Rev. 2009, 38, 3193; b) O.
Baudoin, Eur. J. Org. Chem. 2005, 4223; c) J. M. Brunel, Chem.
Rev. 2005, 105, 857; d) H. Shimizu, I. Nagasaki, T. Saito, Tetra-
ˇ
hedron 2005, 61, 5405; e) P. Kocovský, S. Vyskocil, M. Smrcina,
ˇ
ˇ
ˇ
Chem. Rev. 2003, 103, 3213; f) R. Noyori, Angew. Chem. Int.
Ed. 2002, 41, 2008; g) M. Shibasaki, M. Kanai, K. Funabashi,
Chem. Commun. 2002, 1989; h) I. Ojima, Catalytic Asymmetric
Synthesis, 2nd ed., Wiley, New York, 2000; i) T. Hayashi, Acc.
Chem. Res. 2000, 33, 354; j) L. Pu, Chem. Rev. 1998, 98, 2405.
[2] a) G. Hu, D. Holmes, B. F. Gendhar, W. D. Wulff, J. Am.
Chem. Soc. 2009, 131, 14355; b) X. Li, J. B. Hewgley, C. A.
Mulrooney, J. Yang, M. C. Kozlowski, J. Org. Chem. 2003, 68,
Published Online: December 13, 2010
Eur. J. Org. Chem. 2011, 455–457
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
457