An annulative transfer hydrogenation strategy enables straightforward access to tetrahydro fused-pyrazine derivatives

Article abstract of DOI:10.1039/c6cc05329g

A ruthenium-catalysed annulative transfer hydrogenation strategy, enabling straightforward access to tetrahydro fused-pyrazine derivatives from N-heteroaryl diamines and vicinal diols, has been demonstrated for the first time. Such a synthesis proceeds with unprecedented synthetic effectiveness including high step- and atom efficiency, generation of water as the sole by-product, short reaction time and no need for external high pressure H₂ gas, offering an important basis for the transformation of vicinal diols, a class of bio-mass derived resources, into functionalized products.

Full text of DOI:10.1039/c6cc05329g

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DOI: 10.1039/C6CC05329G
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An annulative transfer hydrogenation strategy enables
straightforward access to tetrahydro fused-pyrazine derivatives
Biao Xiong,a Shu-Di Zhang,a Lu Chen,b Bin Li,b Huan-Feng Jianga and Min Zhang*a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
A ruthenium-catalysed annulative transfer hydrogenation strategy, double/triple bonds.16 (3) Reduction reactions. In which,
enabling straightforward access to tetrahydron fused-pyrazine alcohols were applied as alternative hydrogen sources to
derivatives from N-heteroaryl diamines and vicinal diols, has been reduce unsaturated chemical bonds with liberation of carbonyl
demonstrated for the first time. Such a synthesis proceeds with by-products.17 Despite these important advances, due to the
unprecedented synthetic effectiveness including high step and thermodynamic stability and kinetic inertness of heteroaryl
atom efficiency, generation of water as the sole by-product, short systems, the TH of heteroaromatics with alcohols under
reaction time and no need for external high pressure H2 gas, atmospheric pressure still remains challenging. If such a goal is
offering an important basis for the transformation of vicinal diols, realistic, the envisaged strategy, employing the in-situ formed
a class of bio-mass derived resource, into functionalized products.
carbonyls and hydrogen arising from alcohol dehydrogenation
for new ring construction and TH of heteroaryl ring,
respectively, would shed new light on step- and atom-
economic access to saturated fused-heterocycles that are
currently inaccessible or challenging to prepare with
conventional methods.
Transfer hydrogenation (TH) is a fundamental tool in
obtaining saturated products, which appeals to many synthetic
chemists because it does not need for flammable high
pressure H2 gas, offering more convenient and safer
production processes. During the past decade, a number of
hydrogen donors (i.e. NH3BH3,3 Hantzsch ester,4 HCO2H,5
NaCO2H,6 diboron reagents with water7 and NH2-NH2·H2O8)
have been extensively applied for various synthetic purposes.
In general, these protocols produce stoichiometric amount of
wastes, their applications to large-scale production are easily
restricted.
Upon a thorough literature investigation, it was found that
tetrahydropyrido[2,3-b]pyrazine moiety constitutes the core
structure of numerous functionalized molecules, which exhibit
diverse biological and therapeutic activities such as potent
agonist of the IP receptor, vasodilator, anti-proliferation, anti-
thrombosis and etc.18 However
，the preparation of such
compounds has to date presented a difficult goal. Generally, it
In recent years, the utilization of abundant and sustainable
alcohols for TH reactions has also been elegantly explored.
Representative examples mainly involve: (1) borrowing-
hydrogen reactions.9 Via hydrogenation of the in-situ formed
C-C and C-N double bonds with alcohols, a series of N-
alkylation and C-alkylation methodologies have been reported
by the leading groups of Beller,10 Williams,11 Kempe,12 Fujita,13
Bruneau14 and others15. (2) Transfer hydrogenative coupling
reactions. In this aspect, the Krische group has demonstrated
distinguished contributions on the coupling of alcohols and C-C
was achieved via the condensation of N-heteroaryl 1,2-
diamines
1 with 1,2-diketones 2’ followed by hydrogenation
with H2 (Scheme 1, approach-a), or through a multi-step
procedure (approach-b). Notably, the synthesis required high
pressure H2 gas, high catalyst loading, long reaction time or
complex operations. Therefore, there is
shortcuts to access these valuable compounds.
a demand for
Scheme 1 Conventional synthetic approaches.
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Table 1 Screening of optimal reaction conditions a
The above-described information led us to envisage an
annulative transfer hydrogenation protocol. In which, the
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DOI: 10.1039/C6CC05329G
reaction
initiates
with
transition
metal-catalyzed
dehydrogenation of vicinal diols
condensation with one amino group of N-heteroaryl diamines
2
and subsequent
3aa
,
Entry
Catalyst/mol% Ligand
Base
Yield%b
1
, resulting in two possible imines A-12 or A-12’ and active
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Cat 1/3
Cat 2/3
Cat 3/1
Cat 4/3
Cat 5/3
Cat 6/3
-
L1
L1
L1
L1
L1
L1
L1
L2
L3
L4
L5
L6
L7
L1
L1
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
base
24
31
96
17
35
trace
-
83
[MH2] species19. Then the dehydrogenation of A-12 or A-12’
followed by a condensation gives the annulation adduct B-12
(
path a). Alternatively, a direct dehydrogenation of
ketones followed by condensation with diamines also affords
B-12 path b). Finally, the transfer hydrogenation of B-12 with
[MH2] would afford tetrahydropyridine-fused pyrazine or
pyridine-fused tetrahydropyrazine 3’ Noteworthy, in
2 to di-
1
(
3
.
Cat 3/1
Cat 3/1
Cat 3/1
Cat 3/1
Cat 3/1
Cat 3/1
Cat 3/1
Cat 3/1
comparison with the known procedures (Scheme 1), such a
protocol would not only offer simple operations, but also
produce the products with minimum waste generation.
81
75
90
81
trace
(21, 36, 49)c
(44, 46, 23)d
t-BuOK
a Unless otherwise stated, the reaction was performed with 1a (0.5 mmol), 2a
(0.6 mmol), Cat (3 mol%), ligand (3 mol%), base (50 mol%) in t-amyl alcohol
b
c
(1.2 mL) at 130 oC for 5 h under N2. GC yield of 3aa. Yields are with respect
d
to use of K2CO3, Cs2CO3 and CsOH·H2O as the bases, respectively. Yields are
with respect to use of DMSO, DMF, toluene as the solvents, respectively.
Scheme 2 Envisaged new synthetic strategy.
Scheme 3 Catalysts and ligands tested.
To examine our tentative idea, we performed the reaction
of pyridine-2,3-diamine 1a with butane-2,3-diol 2a in t-amyl
o
alcohol at 130 C for 5 h under N2 protection. In consideration
of the economic attractiveness of ruthenium catalysis, six
catalyst precursors were initially tested by using Xantphos
(Scheme 3, L1) and t-BuOK as the ligand and base, respectively
(Table 1, entries 1-6). Gratifyingly, Ru3(CO)12 gave a tetrahydro
pyridine-fused pyrazine 3aa in almost quantitative yield (96%).
However, the reaction failed to yield any desired product
under catalyst-free conditions (entry 7), indicating that the
presence of ruthenium catalysts plays a crucial role in
Scheme 4 Synthesis of fused-pyrazines. a Isolated yield b Reaction time
With the optimal reaction conditions established, we then
examined the generality of the synthetic protocol. First, the
reactions of pyridine-2,3-diamines (1a, 1b and 1c) with three
symmetrical vicinal diols 2 (2a, 2b and 2c) were tested. As shown in
Scheme 4, all the reactions proceeded smoothly and furnished the
products in moderate to excellent yields upon isolation (3aa-3cc),
and the transfer hydrogenation occurred exclusively on the
sterically less-hindered pyridyl ring, indicating that the steric factor
affording the product. Then, other 6 ligands (Scheme 3, L2-L7)
showed to be either less effective or totally ineffective for the
transformation as compared to Xantphos (Table 1, entries 8-
13). Finally, we checked several other inorganic bases and
solvents (entries 14 and 15), but they are inferior to t-BuOK
and t-amyl alcohol, respectively. Thus, the optimal conditions
are as described in entry 3 of table 1.
2 | J. Name., 2012, 00, 1-3
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plays a crucial role in determining the reduction selectivity. To Scheme 2, and the reduction of such a coupliVniegw aArdticdleuOctnlinies
DOI: 10.1039/C6CC05329G
further prove this conclusion, we performed the reactions of believed to be a rate-determining step.
ethylene glycol 2d with three pyridine-2,3-diamines (1a, 1c and 1d).
The reaction of 1a gave two region-isomers in near 3 : 2 ratio (3ad,
3ad’), whereas 1c afforded the isomers in a ratio of 12 : 88 (3cd,
3cd’). As expected, imidazol substituted diamine 1d yielded a single
product 3dd’ in 41% yield, and the transfer hydrogenation occurred
only on the newly formed pyrazine ring.
Subsequently, we turned our attention to the utilization of
diamines with different substitution patterns in combination
with various vicinal diols (Scheme 5). First, the reactions of two
unsymmetrical diols (2e
isomers (3ae and 3ae’’
,
2f) with 1a gave two couples of regio-
,
3af and 3af’’), and the 3-amino group
of diamine 1a is prone to couple with the sterically less-
hindered -OH site of vicinal diols. Similar to the results
described in Scheme 4, the hydrogen was selectively
transfered to the sterically more accessible pyridyl ring.
Interestingly, glycerol 2g could serve as the equivalent of
propane-1,2-diol to react with 1a, giving the regioisomers 3ag
and 3ag’’ in a ratio of 3 : 1. Then, pyrazine-2,3-diamine 1e, also
underwent smooth annulative transfer hydrogenation
reactions with different diols, affording the desried products in
Figure 1 Representative time course of the reaction of 1a with 2a to
product 3aa under the standard reaction conditions
Finally, we were interested in applying our synthetic
protocol for rapid synthesis of compound 5a, a highly selective
IP receptor agonists used for the treatment of pulmonary
fibrosis.[17] As shown in Scheme 6, tetrahydropyrido[2,3-
b]pyrazine 3ac could be efficiently prepared in 71% yield with
our synthetic protocol. Then, the N-alkylated ester 4a was
synthesized from 3ac and ethyl 6-oxohexanoate by using
moderate to high yields (3eb, 3ec and 3ed). Moreover,
pyridine-3,4-diamine 1f could serve as an effective coupling
partner to react with diol 2a, affording a single product 3fa by
reducing the pyridyl ring, whereas the reaction of 1f and 2d
selectively hydrogenate the newly formed pyrazine ring (3fd’).
(AcO)3BHNa as
a reductant. Ultimately, the ester was
converted into carboxylic acid by refluxing 4a in mixed solvents
in the presence of excess LiOH.
Scheme 6 The utility of the new synthetic protocol.
Conclusions
In summary, we have presented a new ruthenium-catalyzed
annulative transfer hydrogenation strategy, enabling
Scheme 5 Synthesis of various fused-pyrazines. a Isolated yield b Time
To gain insight into the reaction information, a time- straightforward access to a wide range of tetrahydro fused-
concentration profile of the model reaction under standard pyrazine derivatives from N-heteroaryl diamines and vicinal
conditions was depicted in Figure 1. Diamine 1a with diol 2a diols. Such a synthesis proceeds with unprecedented synthetic
was converted into 3aa in a maximum yield (99%) within 5 h. effectiveness including high step- and atom-economic
The growth rate of 3aa and the decreasing rate of 1a were efficiency, generation of water as the sole by-product, no need
very fast within the first 2 h and then became slow. During the for external high pressure H2 gas and short reaction time,
whole reaction, a coupling adduct 2,3-dimethylpyrido[2,3- offering an important basis for the transformation of vicinal
b]pyrazine B-1a2a was formed rapidly in the first half hour and diols, a class of bio-mass derived resource, into functionalized
then was consumed slowly in the remaining 4.5 hours, products. The application of the method was demonstrated by
indicating B-1a2a serves as a key reaction intermediate, which rapid synthesis of a bioactive molecule.
is good in agreement with the reaction pathways proposed in
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Chem. Commun., 2010, 46, 1541-1543; (f) A. J. VAie.wWAratictlseoOnn,linJe.
M. J. Williams, Science, 2010, 329, 635-636.
Acknowledgements
12 (a) S. Roesler, M. Ertl, T. Irrgang, R. DKOemI: 1p0e.1,0A39n/gCe6wCC. 0C5h3e29mG.
Int. Ed., 2015, 54, 15046-15050; (b) T. Hille, T. Irrgang, R.
Kempe, Chem. Eur. J., 2014, 20, 5569-5572;(c) S. Ruch, T.
Irrgang, R. Kempe, Chem. Eur. J., 2014, 20, 13279-13285; (d)
We thank National Natural Science Foundation of China (21472052),
Science Foundation for Distinguished Young Scholars of Guangdong
Province (2014A030306018 + 2015PT018), 1000 Youth Talents Plan,
open fund of State Key Laboratory of Pulp and Paper Engineering of
SCUT (201475), and the Foundation of Department of Education of
Guangdong Province (2014KQNCX156) for financial support.
S. Michlik, T. Hille, R. Kempe, Adv. Synth. Catal., 2012, 354
,
,
847-862; (e) S. Michlik, R. Kempe, Chem. Eur. J., 2010, 16
13193-13198; (e) B. Blank, R. Kempe, J. Am. Chem. Soc.,
2010, 132, 924-925.
13 (a) R. Kawahara, K.-i. Fujita, R. Yamaguchi, J. Am. Chem. Soc.,
2010, 132, 15108-15111; (b) R. Kawahara, K.-i. Fujita, R.
Yamaguchi, Adv. Synth. Catal., 2011, 353, 1161-1168; (c) M.
Zhu, K.-i. Fujita, R. Yamaguchi, Org. Lett., 2010, 12, 1336.
14 (a) N. Kaloglu, I. Ozdemir, N. Gurbuz, M. Achard, C. Bruneau,
Catal. Commun., 2016, 74, 33-38; (b)Z. Sahin, N. Gurbuz, I.
Ozdemir, O. Sahin, O. Buyukgungor, M. Achard, C. Bruneau,
Organometallics, 2015, 34, 2296-2304.
Notes and references
1
(a) J. Goldemberg, Science, 2007, 315, 808-810; (b) S. Michlik
and R. Kempe, Nat. Chem., 2013, , 140-144 (c) J. T.
Kozlowski, R. J. Davis, Acs Catal., 2013, , 1588-1600; (d) C.
Angelici, B. M. Weckhuysen, P. C. A. Bruijnincx,
ChemSusChem, 2013, , 1595-1614.
5
;
3
6
2
3
T. P. Vispute, H. Zhang, A. Sanna, R. Xiao, G. W. Huber,
Science, 2010, 330, 1222-1227.
15 selected examples, see: (a) N. J. Oldenhuis, V. M. Dong, Z.
Guan, J. Am. Chem. Soc., 2014, 136, 12548-12551; (b) S. K.
Murphy, V. M. Dong, J. Am. Chem. Soc., 2013, 135, 5553-
5556; (c) D. Wang, K. Zhao, C. Xu, H. Miao and Y. Ding, Acs
(a) K. A. Erickson, J. P. W. Stelmach, N. T. Mucha, R.
Waterman, Organometallics, 2015, 34, 4693-4699; (b) J. K.
Pagano, J. P. W. Stelmach, R. Waterman, Dalton Trans.,
2015, 44, 12074-12077.
Catalysis, 2014, 4, 3910-3918; (d) S. Demir, F. Coskun and I.
Ozdemir, J. Organomet. Chem., 2014, 755, 134-140; (e) L. J.
Allen and R. H. Crabtree, Green Chem., 2010, 12, 1362-1364;
(f) A. Nova, D. Balcells, N. D. Schley, G. E. Dobereiner, R. H.
Crabtree and O. Eisenstein, Organometallics, 2010, 29, 6548-
4
5
(a) J. K. Pagano, J. P. W. Stelmach, R. Waterman, Dalton
Trans., 2015, 44, 12074-12077; (b) C. R. Shugrue, S. J. Miller,
Angew. Chem. Int. Ed., 2015, 54, 11173-11176.
(a) K. Yuan, F. Jiang, Z. Sahli, M. Achard, T. Roisnel, C.
Bruneau, Angew. Chem. Int. Ed., 2012, 51, 8876-8880; (b) B.
Sundararaju, M. Achard, G. V. M. Sharma, C. Bruneau, J. Am.
6558; (c) J. Norinder and A. Boerner, Chemcatchem, 2011,
3,
1407-1409; (g) N. Andrushko, V. Andrushko, P. Roose, K.
Moonen and A. Boerner, Chemcatchem, 2010, 2, 640-643;
Chem. Soc., 2011, 133
Sundararaju, M. Achard, C. Bruneau, Green Chem., 2013, 15
775-779; (d) B. Sundararaju, Z. Tang, M. Achard, G. V. M.
Sharma, L. Toupet, C. Bruneau, Adv. Synth. Catal., 2010, 352
3141-3146; (e) R. V. Jagadeesh, K. Natte, H. Junge, M. Beller,
Acs Catal., 2015, , 1526-1529 (f) G. Wienhoefer, I. Sorribes,
, 10340-10343; (c) Z. Sahli, B.
(h) L. L. R. Lorentz-Petersen, L. U. Nordstrøm and
,
R. Madsen, Eur. J. Org. Chem., 2012, 34, 6752-6759; (i) R. N.
Monrad and R. Madsen, Org. Biomol. Chem., 2011,
615.
16 Selected very recent contributions of Krische group
9
, 610-
,
：
(a) I.
5
;
Shin, M. J. Krische, in Site-Selective Catalysis, ed. T.
Kawabata, 2016, vol. 372, pp. 85-101; (b) J. Feng, Z. A.
Kasun,M. J. Krische, J. Am. Chem. Soc., 2016, 138, 5467-5478;
A. Boddien, F. Westerhaus, K. Junge, H. Junge, R. Llusar, M.
Beller, J. Am. Chem. Soc., 2011, 133, 12875-12879.
6
7
(a) Z. Chen, H. Zeng, S. A. Girard, F. Wang, N. Chen, C.-J. Li,
Angew. Chem. Int. Ed., 2015, 54, 14487-14491; (b) Z. Chen,
(c) V. J. Garza and M. J. Krische, J. Am. Chem. Soc., 2016, 138
3655-3658; (d) T. Liang, W. Zhang, M. J. Krische, J. Am. Chem.
Soc., 2015, 137 16024-16027; (e) K. D. Nguyen, D.
Herkommer, M. J. Krische, J. Am. Chem. Soc., 2016, 138
,
H. Zeng, H. Gong, H. Wang, C.-J. Li, Chem. Sci., 2015, 6, 4174-
,
4178.
,
A. G. Campana, R. E. Estevez, N. Fuentes, R. Robles, J. M.
5238-5241; (f) F. Perez, A. R. Waldeck, M. J. Krische, Angew.
Chem. Int. Ed., 2016, 55, 5049-5052; (g) A. Saxena, F. Perez,
M. J. Krische, Angew. Chem. Int. Ed., 2016, 55, 1493-1497.
17 Selected examples on reduction of ketones, nitriles, Nitro-
and azobenzenes as well as alkenes, see: (a) W. Zuo, A. J.
Lough, Y. F. Li, R. H. Morris, Science, 2013, 342, 1080-1083;
(b) R. J. Wakeham, J. A. Morris, J. M. J. Williams,
Cuerva, E. Bunuel, D. Cardenas, J. E. Oltra, Org. Lett., 2007, 9,
2195-2198.
8
9
C. Jiang, Z. Shang , X. Liang, Acs Catal., 2015, 5, 4814-4818.
(a) G. E. Dobereiner and R. H. Crabtree, Chem. Rev., 2010,
110, 681-703; G. Guillena, D. J. Ramón, M. Yus, Chem. Rev.
2010, 110, 1611–1641.
10 (a) S. Elangovan, J.-B. Sortais, M. Beller, C. Darcel, Angew.
Chem. Int. Ed., 2015, 54, 14483-14486; (b) M. Pena-Lopez, H.
Neumann, M. Beller, Chem. Commun., 2015, 51, 13082-
13085; (c) S. Baehn, S. Imm, L. Neubert, M. Zhang, H.
ChemCatChem, 2015,
7, 4039-4041; (c) S. Werkmeister, C.
Bornschein, K. Junge, M. Beller, Chem. Eur. J., 2013, 19
,
4437-4440; (d) R. V. Jagadeesh, G. Wienhoefer, F. A.
Westerhaus, A.-E. Surkus, H. Junge, K. Junge, M. Beller,
Chem. Eur. J., 2011, 17, 14375-14379.
Neumann, M. Beller, Chemcatchem, 2011, 3, 1853-1864; (d)
S. Imm, S. Baehn, M. Zhang, L. Neubert, H. Neumann, F.
Klasovsky, J. Pfeffer, T. Haas, M. Beller, Angew. Chem. Int. Ed.,
2011, 50, 7599-7603; (e) M. Zhang, S. Imm, S. Baehn, H.
Neumann, M. Beller, Angew. Chem. Int. Ed., 2011, 50, 11197-
11201; (f) S. Imm, S. Baehn, L. Neubert, H. Neumann, M.
Beller, Angew. Chem. Int. Ed., 2010, 49, 8126-8129.
18 (a) C. Leblanc, S. C. McKeown, A. Perlberg, N. Tufilli,
WO2013/ 105066 A1, 2013; (b) C. Leblanc, S. C. McKeown, S.
J. Charlton, G. Bhalay, M. P. Healy, WO2013/ 105061 A1,
2013; (c) S. J. Charlton, C. Leblanc, S. C. McKeown,
WO2013/105065 A1, 2013; (d) S. J. Charlton, C. Leblanc, S. C.
McKeown, WO2013/105063 A1, 2013; (e) S. J. Charlton, C.
Leblanc, S. C. McKeown, WO2012/7539 A1, 2012.
19 (a) Z. Tan, H. Jiang, M. Zhang, Org. Lett., 2016, 18, 3174-
3177; (b) Z. D. Tan, H. F. Jiang, M. Zhang, Chem. Commun.,
2016, 52, 9359-9362; (c) F. Xie, M. Zhang, H. Jiang, M. Chen,
W. Lv, A. Zheng, X. Jian, Green Chem., 2015, 17, 279-284; (d)
B. Xiong, Y. Li, W. Lv, Z. D. Tan, H. F. Jiang, M. Zhang, Org.
Lett., 2015, 17, 4054-4057; (e) M. Chen, M. Zhang, B. Xiong,
Z. Tan, W. Lv, H. Jiang, Org. Lett., 2014, 16, 6028-6031.
11 (a) W. M. J. Ma, T. D. James, J. M. J. Williams, Org. Lett.,
2013, 15, 4850-4853;(b) A. J. A. Watson, A. C. Maxwell, J. M.
J. Williams, Org. Biomol. Chem., 2012, 10, 240-243; (c) T. D.
Nixon, M. K. Whittlesey, J. M. J. Williams, Tetrahedron Lett.,
2011, 52, 6652-6654;(d) A. J. A. Watson, A. C. Maxwell, J. M.
J. Williams, J. Org. Chem., 2011, 76, 2328-2331; (e) O. Saidi,
A. J. Blacker, M. M. Farah, S. P. Marsden, J. M. J. Williams,
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