10.1002/chem.201705986
Chemistry - A European Journal
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A time resolved 11B-NMR study of the reaction (see Figure 1)
indeed confirms the formation of the borate [B2pin2·Et]ˉ (δ = 4.8
ppm), EtBpin (δ = 34.5 ppm) and HOBpin (δ = 21.8 ppm) along
with the aminoborane product 4w (δ = 24.1 ppm).
Dixon, B. E. Looker, Synlett 2005, 2005, 1948-1950; f) B. Ghavimi, P.
Magnus, Org. Lett. 2014, 16, 1708-1711.
[4]
a) S. E. Denmark, M. Xie, J. Org. Chem. 2007, 72, 7050-7053; b) B. List,
P. Pojarliev, H. J. Martin, Org. Lett. 2001, 3, 2423-2425; c) A. Dornow, A.
Frese, Liebigs Ann. Chem. 1952, 578, 122-136; d) T. Stemmler, F. A.
Westerhaus, A.-E. Surkus, M.-M. Pohl, K. Junge, M. Beller, Green Chem.
2014, 16, 4535-4540; e) R. Nacario, S. Kotakonda, D. M. D. Fouchard,
L. M. V. Tillekeratne, R. A. Hudson, Org. Lett. 2005, 7, 471-474; f) K.
Busch, U. M. Groth, W. Kühnle, U. Schöllkopf, Tetrahedron 1992, 48,
5607-5618; g) P. Zhou, Z. Zehui, ChemSusChem 2017, 10, 1892; h) L.
Yu, Q. Zhang, S. S. Li, J. Huang, Y. M. Liu, H. Y. He, Y. Cao,
ChemSusChem 2015, 8, 3029. i) E. Pedrajas, I. Sorribes, K. Junge, M.
Beller, R. Llusar, Green Chem. 2017, 19, 3764.
The difference between functionalization of aliphatic and aromatic
nitro compounds was not only observed during the optimization
but also during the mechanistic investigations: The intensity of the
aminoborane signal is weak, despite the high yield of isolated
amine/amide. Furthermore, two new borate signals (δ = 5.7 / 6.9
ppm) were observed. Throughout the reaction the intensity of both
signals increases at the same rate as the aminoborane signal.
Upon hydrolysis the signal at δ = 5.7 ppm vanishes and the one
at 6.9 ppm remains. We propose an assignment of the signal at δ
= 5.7 ppm to a dimeric aminoborane 9. A dimer of this type was
not observed in the electrophilic amination of nitroarenes.
[5]
a) I. Sapountzis, P. Knochel, J. Am. Chem. Soc. 2002, 124, 9390-9391;
b) H. Gao, D. H. Ess, M. Yousufuddin, L. Kurti, J. Am. Chem. Soc. 2013,
135, 7086-7089; c) L. Wylie, P. Innocenti, D. K. Whelligan, S. Hoelder,
Org. Biomol. Chem. 2012, 10, 4441-4447; d) G. Bartoli, E. Marcantoni,
M. Petrini, J. Chem. Soc., Chem. Commun. 1993, 1373-1374; e) M.
Bosco, R. Dalpozzo, G. Bartoli, G. Palmieri, M. Petrini, J. Chem. Soc.,
Perkin Trans. 2 1991, 657-663; f) P. Knochel, V. Dhayalan, Synthesis
2015, 47, 3246-3256; g) Z. Huang, J. Lv, Y. Jia, ChemistrySelect 2016,
1, 5892-5894.
Comparison with literature data allowed for
a tentative
assignment of the signal at δ = 6.9 ppm to [Bpin2]¯ which might
form as a decomposition product[15] during the activation of B2pin2
(see SI for details). Control experiments with oxime 3 and
hydroxylamine 8 as potential mechanistic intermediates in
alternative pathways support the proposed mechanism (see SI for
details).
[6]
a) J. Gui, C.-M. Pan, Y. Jin, T. Qin, J. C. Lo, B. J. Lee, S. H. Spergel, M.
E. Mertzman, W. J. Pitts, T. E. La Cruz, M. A. Schmidt, N. Darvatkar, S.
R. Natarajan, P. S. Baran, Science 2015, 348, 886-891; b) C. W. Cheung,
X. Hu, Nat. Commun. 2016, 7, 12494; c) S. Tong, Z. Xu, M. Mamboury,
Q. Wang, J. Zhu, Angew. Chem. Int. Ed. 2015, 54, 11809-11812; d) M.
Villa, A. Jacobi von Wangelin, Angew. Chem. Int. Ed. 2015, 54, 11906-
11908; e) F. Zhao, B. Li, H. Huang, G.-J. Deng, RSC Adv. 2016, 6,
13010-13013; f) K. Zhu, M. P. Shaver, S. P. Thomas, Chem. Sci. 2016,
7, 3031-3035; g) K. Zhu, M. P. Shaver, S. P. Thomas, Chem. Asian. J.
2016, 11, 977-980.
All known approaches for a direct N-functionalization of nitro
compounds without the detour to the fully reduced amine proceed
via nitroso intermediates. Therefore, transformation of aliphatic
nitro groups remained severely limited, due to the rapid nitroso-
oxime tautomerization. This restriction was overcome by a
customization of our previous protocol for a partial reduction of
the nitro group to a nitrenoid as a more stable intermediate. This
nitrenoid is harnessed in-situ, as an aminating reagent for the
electrophilic amination with primary, secondary and tertiary
aliphatic nitro compounds. The protocol was realized via a readily
available and mild combination of B2pin2 and zinc organyls. Many
functional groups, such as halogens, esters or alcohols are well
tolerated, as demonstrated by an extensive scope. Furthermore,
a complementary robustness screen, indicates for the method’s
applicability to complex substrates, amino acids, heterocycles
and aliphatic alcohols. The mild reaction conditions and generality
of the protocol make it ideally suited for late stage transformations
of aliphatic nitro groups into functionalized amines.
[7]
[8]
[9]
a) C. D. Weis, G. R. Newkome, Synthesis 1995, 1995, 1053-1065; b) C.
Czekelius, E. M. Carreira, Angew. Chem. Int. Ed. 2005, 44, 612-615; c)
K. Kuciński, G. Hreczycho, Eur. J. Org. Chem. 2016, 2016, 4577-4585;
d) J. A. Long, N. J. Harris, K. Lammertsma, J. Org. Chem. 2001, 66,
6762-6767.
a) J. Zhou, F. Zhou, F.-M. Liao, J.-S. Yu, Synthesis 2014, 46, 2983-3003;
b) E. Jarvo, T. Barker, Synthesis 2011, 2011, 3954-3964; c) C. Gosmini,
M. Corpet, Synthesis 2014, 46, 2258-2271; d) X. Dong, Q. Liu, Y. Dong,
H. Liu, Chem. Eur. J. 2017, 23, 2481-2511; e) A. M. Berman, J. S.
Johnson, J. Am. Chem. Soc. 2004, 126, 5680-5681.
K. Oshima, T. Ohmura, M. Suginome, J. Am. Chem. Soc. 2012, 134,
3699-3702.
[10] The direct treatment of aminoboranes with acetyl chloride gave mixed
results. This is presumably due to a dimerization of the aminoborane (see
SI for details). Therefore a hydrolytic work-up was followed by treatment
of the crude reaction mixture with AcCl.
[11] A. E. Jensen, P. Knochel, J. Org. Chem. 2002, 67, 79-85.
[12] a) K. D. Collins, F. Glorius, Nat. Chem. 2013, 5, 597-601; b) A. A. Toutov,
W. B. Liu, K. N. Betz, B. M. Stoltz, R. H. Grubbs, Nat. Protoc. 2015, 10,
1897-1903.
Keywords: aminoboranes • nitro functionalization • electrophilic
amination • nitrenoid • nucleophilic boron
[13] a) P. Starkov, T. F. Jamison, I. Marek, Chem. Eur. J. 2015, 21, 5278-
5300; b) C. Zhu, G. Li, D. H. Ess, J. R. Falck, L. Kürti, J. Am. Chem. Soc.
2012, 134, 18253-18256; c) S. N. Mlynarski, A. S. Karns, J. P. Morken,
J. Am. Chem. Soc. 2012, 134, 16449-16451; d) G. Boche, J. C. W.
Lohrenz, Chem. Rev. 2001, 101, 697-756.
[1]
a) T. E. Müller, K. C. Hultzsch, M. Yus, F. Foubelo, M. Tada, Chem. Rev.
2008, 108, 3795-3892; b) J. F. Hartwig, Acc. Chem. Res. 2008, 41, 1534-
1544; c) S. Gomez, J. A. Peters, T. Maschmeyer, Adv. Synth. Catal. 2002,
344, 1037-1057; d) S. H. Cho, J. Y. Kim, J. Kwak, S. Chang, Chem. Soc.
Rev. 2011, 40, 5068-5083.
[14] a) J. L. Stymiest, V. Bagutski, R. M. French, V. K. Aggarwal, Nature 2008,
456, 778-782; b) Phanstiel, Q. X. Wang, D. H. Powell, M. P. Ospina, B.
A. Leeson, J. Org. Chem. 1999, 64, 803-806; c) G. A. Molander, J.
Raushel, N. M. Ellis, J. Org. Chem. 2010, 75, 4304-4306; d) A. Casarini,
P. Dembech, D. Lazzari, E. Marini, G. Reginato, A. Ricci, G. Seconi, J.
Org. Chem. 1993, 58, 5620-5623; e) H. C. Brown, W. R. Heydkamp, E.
Breuer, W. S. Murphy, J. Am. Chem. Soc. 1964, 86, 3565-3566.
[15] C. Kleeberg, A. G. Crawford, A. S. Batsanov, P. Hodgkinson, D. C.
Apperley, M. S. Cheung, Z. Lin, T. B. Marder, J. Org. Chem. 2012, 77,
785-789.
[2]
[3]
a) M. Orlandi, D. Brenna, R. Harms, S. Jost, M. Benaglia, Org. Process
Res. Dev. 2016; b) K. Soai, A. Ookawa, J. Org. Chem. 1986, 51, 4000-
4005; c) J. F. Knifton, J. Org. Chem. 1975, 40, 519-520; d) M. Baron, E.
Métay, M. Lemaire, F. Popowycz, Green Chem. 2013, 15, 1006.
a) R. Ballini; E. Marcantoni; M. Petrini, in Amino Group Chemistry, Wiley-
VCH: Weinheim 2008; pp 93-148; b) S. B. Markofsky, in Ullmann's
Encyclopedia of Industrial Chemistry, Wiley-VCH: Weinheim 2011, pp
291; c) R. S. Fornicola, E. Oblinger, J. Montgomery, J. Org. Chem. 1998,
63, 3528-3529; d) D. J. Buchanan, D. J. Dixon, M. S. Scott, D. I. Lainé,
Tetrahedron: Asymmetry 2004, 15, 195-197; e) D. J. Buchanan, D. J.
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