Ligand-controlled regiodivergent nickel-catalyzed annulation of pyridones

Article abstract of DOI:10.1002/anie.201409669

The 1,6-annulated 2-pyridone motif is found in many biologically active compounds and its close relation to the indolizidine and quinolizidine alkaloid core makes it an attractive building block. A nickel-catalyzed C-H functionalization of 2-pyridones and subsequent cyclization affords 1,6-annulated 2-pyridones by selective intramolecular olefin hydroarylation. The switch between the exo- and endocyclization modes is controlled by two complementary sets of ligands. Irrespective of the ring size, the regioselectivity during the cyclization is under full catalyst control. Simple cyclooctadiene promotes an exo-selective cyclization, whereas a bulky N-heterocyclic carbene ligand results in an endoselective mode. The method was further applied in the synthesis of the lupin alkaloid cytisine.

Full text of DOI:10.1002/anie.201409669

Angewandte
Chemie
DOI: 10.1002/anie.201409669
À
C H Activation
Hot Paper
Ligand-Controlled Regiodivergent Nickel-Catalyzed Annulation of
Pyridones**
Pavel A. Donets and Nicolai Cramer*
Abstract: The 1,6-annulated 2-pyridone motif is found in
many biologically active compounds and its close relation to
the indolizidine and quinolizidine alkaloid core makes it an
À
attractive building block. A nickel-catalyzed C H functional-
ization of 2-pyridones and subsequent cyclization affords 1,6-
annulated 2-pyridones by selective intramolecular olefin
hydroarylation. The switch between the exo- and endo-
cyclization modes is controlled by two complementary sets of
ligands. Irrespective of the ring size, the regioselectivity during
the cyclization is under full catalyst control. Simple cyclo-
octadiene promotes an exo-selective cyclization, whereas
a bulky N-heterocyclic carbene ligand results in an endo-
selective mode. The method was further applied in the synthesis
of the lupin alkaloid cytisine.
T
he 2-pyridone structural motif is common[1] in natural
products and pharmacologically potent compounds display-
ing a diversity of properties such as anti-tumor,[2a] antimicro-
bial,[2b] anti-inflammatory,[2c] cardiotonic,[2d] and antiviral[2e]
activity. An important subclass of 2-pyridone derivatives,
including several biologically active natural products,[3] con-
tains a 1,6-carboannulated 2-pyridone ring (Figure 1). Besides
their high significance for medicinal chemistry, annulated 2-
pyridones can serve as valuable intermediates for the syn-
thesis of bioactive indolizidine and quinolizidine alkaloids.[4]
Camptothecine-like annulation patterns of an aromatic
ring linked to the pyridone core are accessible by intra-
molecular Heck reactions.[5] In contrast, annulations with
saturated cycles have been accomplished by radical cycliza-
tion methods[6] or nucleophilic 1,6-addition[7] followed by
rearomatization. However, both methods require additional
steps for a separate installation of the reacting functional
group (an iodide or an amide correspondingly) for the
initiation of the cyclization. Moreover, they lack flexibility
since the ring size of the appended cycle strictly depends on
the position of the functional group in the side-chain of the
substrate. A powerful C6-selective method for alkenylation[8a]
Figure 1. Bioactive 1,6-annulated 2-pyridone natural products.
hydroarylation,[9] employing cooperative nickel(0)/Lewis
acid catalysis,[10] has been developed by Nakao, Hiyama,
and co-workers. The two reported examples of an intra-
molecular alkylation afforded mostly the exo-cyclization
products and showed ring-size-dependent differences in
selectivity (Scheme 1). Principally, both ends of the double
bond could react, thus resulting in the formation of either exo-
or endo-cyclization products. Whereas often one pathway is
preferred,[11] control and switch of the cyclization modes is
desirable, but often very challenging.[12] For instance, hydro-
and alkylation[8b] of pyridones by C H activation/olefin
À
[*] Dr. P. A. Donets, Prof. Dr. N. Cramer
Laboratory of Asymmetric Catalysis and Synthesis
EPFL SB ISIC LCSA
BCH 4305, 1015 Lausanne (Switzerland)
E-mail: Nicolai.cramer@epfl.ch
Homepage: http://isic.epfl.ch/lcsa
[**] This work is supported by the European Research Council under the
European Community’s Seventh Framework Program (FP7 2007–
2013)/ERC Grant agreement no. 257891 and the Swiss National
Science Foundation (no. 155967).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201409669.
Scheme 1. Intramolecular 2-pyridone hydroarylation. cod=1,5-cyclo-
octadiene.
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metalations proceed generally in a Markovnikov fashion[13]
and preferentially place the metal at the least substituted
carbon atom. Thus, besides the ring size formed, the
regioselectivity of the cyclization should be expected to
depend strongly on the olefin substitution pattern. Ideally,
suitable steering ligands would be able to override both of
these intrinsic substrate controls and allow predictable
switching between endo- and exo-cyclization modes
(Scheme 1). Intrigued by the perspective of an efficient and
versatile access to 1,6-annulated 2-pyridones suitable for
concise assembly of pyridone natural products, we decided to
investigate the nickel(0)-catalyzed intramolecular hydroary-
lation in greater detail. Herein, we report our findings using
different ligand sets to fully control and to effect selectively
either exo or endo cyclization during the olefin hydrometa-
lation step.
good yield, thus surpassing the efficiency of the reaction with
a phosphine (entry 5). Other aluminum-based Lewis acids
like AlEt3 or MAD[15] were inefficient as cocatalysts (entries 6
and 7). Although [Ni(cod)2] is an efficient cyclization catalyst,
phosphine/nickel(0) complexes also deliver competent cata-
lytic species, as [(Cy3P)2Ni(C2H4)][16] displayed similar reac-
tivity to that of the [Ni(cod)2]/phosphine combinations
(entry 8). Importantly, the selectivity mode of the cyclization
completely switched when using an N-heterocyclic carbene
(NHC) ligand (IMes) under otherwise identical reaction
conditions (entry 9). The preformed complex [IMes2Ni][17]
performed similarly to the in situ [Ni(cod)2]/IMes combina-
tion, thus indicating little contribution of cod ligand to the
catalytic activity in this case (entry 10). The bulkier IPr ligand
afforded a higher overall reaction yield albeit with a margin-
ally lower selectivity (entry 11). Both parameters could be
improved in the presence of MAD (entry 12). Interestingly,
the usage of saturated analogue SIPr led to a significant
erosion of the selectivity and drop in the yield (entry 13).
With the two sets of reaction conditions for a powerful
switch between endo/exo cyclization modes, the scope of the
cyclization was evaluated (Table 2). Notably, exclusive for-
mation of either product 2 or 3 could be attained for all the
substrates 1 independent of their structure. For some instan-
ces, slight fine-tuning of the reaction conditions was required
to enhance the selectivity. The deuterated 6-D-pyridone 1b
underwent complete deuterium transfer to the methyl group
of 2b in the exo-cyclization mode and to the methylene group
of 3b in the endo-cyclization mode. These findings strongly
We initiated our studies with the cyclization of the
pyridone 1a bearing an unbiased 1,2-disubstituted double
bond (Table 1). Monodentate phosphine ligands provided
Table 1: Optimization of the regiodivergent cyclization.[a]
Entry
Ligand[b]
Lewis acid
Yield [%][c]
2a/3a[c]
1
2
3
4
5
6
(iPr)3P
(tBu)3P
Cy3P
(Cy2PCH2)2
–
–
AlMe3
AlMe3
AlMe3
AlMe3
AlMe3
AlEt3
70
68
70
0
83 (80)
0
>95:5
>95:5
>95:5
–
>95:5
–
À
support the C6 H nickel(0) insertion/hydroarylation mecha-
nism suggested by Nakao, Hiyama, and co-workers.[8] More-
over, the absence of any deuterium scrambling indicates an
irreversible hydroarylation step. The exo cyclization of 1c,
bearing an existing stereogenic center in the tether, provided
the more stable trans-product 2c with a 4:1 selectivity. Most
substrates bearing 1,2-disubstitited double bonds were effi-
ciently transformed through both cyclization modes, thus
affording the corresponding pyridones 2d–f and 3d–f. Inter-
estingly, trans-1d showed a higher reactivity than the corre-
sponding cis-1d (entries 3 and 4), despite the presumed
higher affinity of the latter to the metal center.[18] The
pyridone 1 f underwent smooth cyclizations in both modes to
give the cis-fused tricycle 2 f as well as the bridged tricycle 3 f
(entry 6). The related N-Boc-containing substrate 1g worked
efficiently in the exo mode, but failed to give the endo-
cyclization product, probably because of the bulk of the N-
Boc moiety (entry 7). The substrate 1h, containing a 1,1-
dialkyl-substituted olefin, smoothly delivered the endo-prod-
uct 3h. In this case, the exo cyclization was not possible, and is
likely to be the result of the congested nickelacycle with the
metal at the tertiary carbon atom.[19] Along the same lines,
trialkyl-substituted olefins (1i and 1j) are competent as long
as it does not involve a nickel/tertiary carbon organometallic
intermediate (entries 8 and 9). In contrast, the formation of
quaternary carbon centers is possible with aryl-substituted
olefins (entries 11–14), thus indicating a stabilization via a h3-
benzylic-nickel intermediate.[8,20] The endo cyclization of 1n
produced the trans-product 3n in moderate diastereoselec-
tivity (entry 14). The minor cis isomer is probably formed
7
–
MAD
0
–
8
9
10
11
12
13
(Cy3P)2Ni(C2H4)
AlMe3
AlMe3
AlMe3
AlMe3
MAD
68
70
63
77 (70)
81 (74)
55
>95:5
>5:95
>5:95
6:94
>5:95
15:85
IMes
IMes2Ni
IPr
IPr
SIPr
AlMe3
[a] 0.10 mmol of 1a, 10 mol% [Ni(cod)2], 40 mol% LA, toluene (0.4 mL),
808C for 24 h. [b] 25 mol% monodentate phosphine, 15 mol% bidentate
phosphine or NHC, 10 mol% nickel complex. [c] Determined by 1H NMR
spectroscopy using 1,3,5-trimethoxybenzene as an internal standard.
Yield of isolated product given within parentheses. LA=Lewis acid,
MAD=see Ref. [15].
excellent exo selectivity in the reaction of 1a (entries 1–3)
with [Ni(cod)2] as a metal source and AlMe3 as Lewis acid.[8]
Surprisingly, the yield of 2a was almost independent of the
phosphine structure. Moreover, the bidentate ligand
[(Cy2PCH2)2] completely inhibited the reaction (entry 4).
This observation prompted us to investigate whether [Ni-
(cod)2] might be solely responsible for the reactivity. The
Lewis acid present in the reaction might potentially bind the
free phosphine resulting from dissociation[14] of the initially
formed nickel(0) complex, thus shifting the equilibrium to
[Ni(cod)2]. Indeed, omitting the phosphine ligand in the
reaction exclusively delivered the exo product 2a with very
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Table 2: Scope of regioselective cyclization.[a]
Table 2: (Continued)
Entry
Substrate 1
2[b]
3[b]
14
Entry
1
Substrate 1
2[b]
3[b]
15
n.r.[e]
16
17
2
3
4
n.r.[e]
[a] Conditions A: 0.10 mmol of 1, 10 mol% [Ni(cod)2], 40 mol% AlMe3,
toluene (0.4 mL), 808C for 24 h; Conditions B: 0.10 mmol of 1, 10 mol%
[Ni(cod)2], 15 mol% IPr, 40 mol% AlMe3, toluene (0.4 mL), 808C for
24 h. [b] Yield of isolated product. [c] MAD instead of AlMe3. [d] IMes
instead of IPr. [e] No conversion. [f] 1008C. Boc=tert-butoxycarbonyl,
PMP=para-methoxyphenyl.
because of the concomitant double bond isomerization of 1n
[21,22]
À
promoted by the Ni H species.
The medium-sized rings
5
6
3m,o could be selectively obtained by endo cyclization
(entries 13 and 15). Besides pyridones, the uracil 1p is
a competent substrate (entry 16). The benzopyridone 1q
gave endo-cyclization product 3q in excellent yield, however
failed in the exo mode as a result of rapid catalyst degradation
(entry 16).
To showcase the viability of the developed cyclization for
the synthesis of naturally occurring compounds, we turned
our attention to the lupin alkaloid cytisine occurring in many
leguminosae (Scheme 2).[23] (À)-Cytisine was identified as
a potent and selective partial agonist for the a4b2 neuronal
nicotinic acetylcholine receptor.[24] While smoothly reacting
in the exo mode, the Boc-protected substrate 1g previously
failed for the endo-cyclization mode (Table 2, entry 7).
Pleasingly, switching the Boc group for a benzoyl group (1r)
enabled successful endo cyclization (Scheme 2). Higher
7
8
n.r.[e]
n.r.[e]
n.r.[e]
9
10
11
12
n.r.[f]
Scheme 2. Application of the endo-cyclization mode for the synthesis
of the lupin alkaloid (Æ)-cytisine. brsm=based on recovered starting
material, Bz=benzoyl.
13
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Lo Presti, R. Boggia, A. Feltrin, G. Menozzi, P. Dorigo, L. Mosti,
Farmaco 1999, 54, 465 – 474; e) P. S. Dragovich et al., J. Med.
Chem. 2002, 45, 1607 – 1623;f) X. Fan, D. Feng, Y. Qu, X. Zhang,
J. Wang, P. M. Loiseau, G. Andrei, R. Snoeck, E. De Clercq,
Bioorg. Med. Chem. Lett. 2010, 20, 809 – 813.
amounts of Lewis acid were necessary to drive the cyclization
to a better conversion, thus giving 3r in acceptable yield.
Acidic cleavage of the benzoyl group proceeded smoothly,
thus affording (Æ)-cytisine in high yield.
We next explored the possibility to conduct the endo-
cyclization mode[25] in enantioselective fashion using a chiral
N-heterocyclic carbene[26] as a steering ligand. For instance,
reaction of 1h and 1i in the presence of [Ni(cod)2], AlMe3,
and a chiral N-heterocyclic carbene (L*) based on the
isoquinoline framework developed by Hong et al.[27] delivered
the corresponding enantioenriched pyridones (À)-3h and
(À)-3i in 78.5:21.5 e.r. (Scheme 3).
[3] Camptothecin: M. E. Wall, M. C. Wani, C. E. Cook, K. H.
Palmer, J. Am. Chem. Soc. 1966, 88, 3888 – 3890; Leuconicines:
C.-Y. Gan, Y.-Y. Low, T. Etoh, M. Hayashi, K. Komiyama, T.-S.
Kam, J. Nat. Prod. 2009, 72, 2098 – 2103; Sophoramine: H. Hu, S.
Wang, C. Zhang, L. Wang, L. Ding, J. Zhang, Q. Wu, Bioorg.
Med. Chem. Lett. 2010, 20, 7537 – 7539; Thermopsine: S.
Ohmiya, H. Otomasu, J. Haginiwa, I. Murakoshi, Phytochemis-
try 1984, 23, 2665 – 2668.
[4] a) J. P. Michael, Nat. Prod. Rep. 2007, 24, 191 – 222; b) J. P.
Michael, Nat. Prod. Rep. 2008, 25, 139 – 165.
[5] a) S. Yu, Q.-Q. Huang, Y. Luo, W. Lu, J. Org. Chem. 2012, 77,
713 – 717; b) V. A. Bacherikov, T.-J. Tsai, J.-Y. Chang, T.-C.
Chou, R.-Z. Lee, T.-L. Su, Eur. J. Org. Chem. 2006, 4490 – 4499;
c) O. Lavergne, D. Demarquay, C. Bailly, C. Lanco, A. Rolland,
M. Huchet, H. Coulomb, N. Muller, N. Baroggi, J. Camara, C.
Le Breton, E. Manginot, J.-B. Cazaux, D. C. H. Bigg, J. Med.
Chem. 2000, 43, 2285 – 2289.
[6] a) M. Menes-Arzate, R. Martꢀnez, R. Cruz-Almanza, J. M.
Muchowski, Y. M. Osornio, L. D. Miranda, J. Org. Chem. 2004,
69, 4001 – 4004; b) Y. M. Osornio, L. D. Miranda, R. Cruz-
Almanzaa, J. M. Muchowski, Tetrahedron Lett. 2004, 45, 2855 –
2858.
Scheme 3. Preliminary results towards a catalytic asymmetric version
of the endo cyclization with a chiral NHC ligand.
[7] a) T. Gallagher, I. Derrick, P. M. Durkin, C. A. Haseler, C.
Hirschhꢁuser, P. Magrone, J. Org. Chem. 2010, 75, 3766 – 3774;
b) P. Durkin, P. Magrone, S. Matthews, C. Dallanoce, T.
Gallagher, Synlett 2010, 2789 – 2791; c) D. Gray, T. Gallagher,
Angew. Chem. Int. Ed. 2006, 45, 2419 – 2423; Angew. Chem.
2006, 118, 2479 – 2483.
[8] a) Y. Nakao, H. Idei, K. S. Kanyiva, T. Hiyama, J. Am. Chem.
Soc. 2009, 131, 15996 – 15997; b) R. Tamura, Y. Yamada, Y.
Nakao, T. Hiyama, Angew. Chem. Int. Ed. 2012, 51, 5679 – 5682;
Angew. Chem. 2012, 124, 5777 – 5780.
In summary, we report a regiodivergent and highly
selective synthesis of 1,6-annulated 2-pyridones by intra-
molecular nickel(0)-catalyzed cyclization. The regioselectiv-
ity of the cyclization is fully controlled by the ligand and
virtually independent of the ring size and olefin substitution
pattern. Reaction in the presence of cyclooctadiene exclu-
sively delivers exo-cyclization products, whereas bulky NHC
ligands selectively promote the endo-cyclization mode. Nota-
bly, the method enables facile construction of quaternary
carbon centers, medium-sized rings, and bicyclo[3.3.1]nonane
skeletons. Relatively labile functional groups such as an
acetonide and a Boc group are well tolerated. Moreover, the
utility of transformation was exemplified by a concise syn-
thesis of lupin alkaloid (Æ)-cytisine. Further work is directed
towards the development of a more efficient asymmetric
process and its application to the synthesis of 2-pyridone
natural products.
À
[9] For C H functionalizations of pyridones, also see: a) T. Itahara,
F. Ouseto, Synthesis 1984, 488 – 489; b) Y. Chen, F. Wang, A. Jia,
X. Li, Chem. Sci. 2012, 3, 3231 – 3236; c) A. Nakatani, K. Hirano,
T. Satoh, M. Miura, Chem. Eur. J. 2013, 19, 7691 – 7695; d) A.
Nakatani, K. Hirano, T. Satoh, M. Miura, J. Org. Chem. 2014, 79,
1377 – 1385; e) E. E. Anagnostaki, A. D. Fotiadou, V. Demer-
tzidou, A. L. Zografos, Chem. Commun. 2014, 50, 6879 – 6882;
f) R. Odani, K. Hirano, T. Satoh, M. Miura, Angew. Chem. Int.
Ed. 2014, 53, 10784 – 10788; Angew. Chem. 2014, 126, 10960 –
10964.
[10] For reviews on Lewis acid/transition-metal cooperative catalysis,
see: a) C. Wang, Z. Xi, Chem. Soc. Rev. 2007, 36, 1395 – 1406;
b) A. Yada, S. Ebata, H. Idei, D. Zhang, Y. Nakao, T. Hiyama,
Bull. Chem. Soc. Jpn. 2010, 83, 1170 – 1184; c) P. Li, H.
Yamamoto, Top. Organomet. Chem. 2011, 37, 161 – 183.
[11] a) C. D. Johnson, Acc. Chem. Res. 1993, 26, 476 – 482; b) K.
Gilmore, I. V. Alabugin, Chem. Rev. 2011, 111, 6513 – 6556.
[12] J. Mahatthananchai, A. M. Dumas, J. W. Bode, Angew. Chem.
Int. Ed. 2012, 51, 10954 – 10990; Angew. Chem. 2012, 124, 11114 –
11152.
[13] U. M. Dzhemilev, A. G. Ibragimov in Modern Reduction Meth-
ods (Eds.: P. G. Andersson, I. J. Munslow), Wiley-VCH, Wein-
heim, 2008; pp. 447 – 489.
[14] Ligand dissociations in iPr3P/Ni systems: a) R. Beck, S. A.
Johnson, Organometallics 2012, 31, 3599 – 3609; b) R. Beck, M.
Shoshani, J. Krasinkiewicz, J. A. Hatnean, S. A. Johnson, Dalton
Trans. 2013, 42, 1461 – 1475.
Received: October 1, 2014
Published online: November 6, 2014
À
Keywords: C H activation · cyclization · heterocycles ·
N-heterocyclic carbenes · nickel
.
[1] M. Torres, S. Gil, M. Parra, Curr. Org. Chem. 2005, 9, 1757 – 1779.
[2] a) Q. Li, A. Claiborne, T. Li, L. Hasvold, V. S. Stoll, S.
Muchmore, C. G. Jakob, W. Gu, J. Cohen, C. Hutchins, D.
Frost, S. H. Rosenberg, H. L. Sham, Bioorg. Med. Chem. Lett.
2004, 14, 5367 – 5370; M. T. Cocco, C. Congiu, V. Onnis, Eur. J.
Med. Chem. 2000, 35, 545 – 552; b) H. M. Hassanin, S. M. El-
Edfawy, Heterocycles 2012, 85, 2421 – 2436; c) A. G. E. Amr,
M. M. Abdulla, Bioorg. Med. Chem. 2006, 14, 4341 – 4352; d) E.
[15] Methylaluminum bis(2,6-di-tert-butyl 4-methylphenoxide): K.
Maruoka, T. Itoh, H. Yamamoto, J. Am. Chem. Soc. 1985, 107,
4573 – 4576.
636
www.angewandte.org
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Angewandte
Chemie
[16] P. W. Jolly, K. Jonas, Inorg. Synth. 1974, 15, 29 – 31.
[17] A. J. Arduengo III, S. F. Gamper, J. C. Calabrese, F. Davidson, J.
Am. Chem. Soc. 1994, 116, 4391 – 4394.
[18] a) C. A. Tolman, Organometallics 1983, 2, 614 – 621; b) C. A.
Tolman, J. Am. Chem. Soc. 1974, 96, 2780 – 2789.
[19] The only example of a similar metallacycle resulting from
hydrometalation has been implied in intramolecular cobalt-
catalyzed olefin hydroarylation: Z. Ding, N. Yoshikai, Angew.
Chem. Int. Ed. 2013, 52, 8574 – 8578; Angew. Chem. 2013, 125,
8736 – 8740.
Maurer, G. Raabe, Angew. Chem. Int. Ed. 2001, 40, 177 – 179;
Angew. Chem. 2001, 113, 176 – 178.
[22] Reaction in the presence of AlMe3 resulted in lower conversion
(55%) of 1n and concomitant formation of (Z)-1n (6%).
[23] N. J. Leonard in The Alkaloids, Vol. 3 (Eds.: R. H. F. Manske,
H. L. Holmes), Academic Press, New York, 1953, pp. 119 – 199.
[24] A. A. Jensen, B. Frølund, T. Liljefors, P. Krogsgaard-Larsen, J.
Med. Chem. 2005, 48, 4705 – 4745.
[25] Preliminary attempts to effect an enantioselective exo cycliza-
tion by chiral diene ligands failed.
[20] Y. Nakao, N. Kashihara, K. S. Kanyiva, T. Hiyama, Angew.
Chem. Int. Ed. 2010, 49, 4451 – 4454; Angew. Chem. 2010, 122,
4553 – 4556.
[26] For recent reviews, see: a) M. N. Hopkinson, C. Richter, M.
Schedler, F. Glorius, Nature 2014, 510, 485 – 496; b) F. Wang, L.-J.
Liu, W. Wang, S. Li, M. Shi, Coord. Chem. Rev. 2012, 256, 804 –
853.
[27] D. Hirsch-Weil, K. A. Abboud, S. Hong, Chem. Commun. 2010,
46, 7525 – 7527.
À
[21] For olefin isomerization promoted by Ni H species, see: a) H. J.
Lim, C. R. Smith, T. V. RajanBabu, J. Org. Chem. 2009, 74,
4565 – 4572; b) H. Frauenrath, D. Brethauer, S. Reim, M.
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