Cobalt-mediated regio- and stereoselective assembly of dienamides by hydroaminative alkyne coupling of α,ω-diynes

Article abstract of DOI:10.1039/b716841a

In the presence of CpCo(C₂H₄)₂, α,ω-diynes undergo hydroaminative coupling with amides to furnish new dienamides with control of regio- and stereochemistry. The Royal Society of Chemistry.

Full text of DOI:10.1039/b716841a

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Cobalt-mediated regio- and stereoselective assembly of dienamides by
hydroaminative alkyne coupling of a,x-diynesw
Vincent Gandon,ab Corinne Aubert,b Max Malacriab and K. Peter C. Vollhardt*a
Received (in Cambridge, UK) 31st October 2007, Accepted 15th January 2008
First published as an Advance Article on the web 27th February 2008
DOI: 10.1039/b716841a
In the presence of CpCo(C2H4)2, a,x-diynes undergo hydro-
aminative coupling with amides to furnish new dienamides with
control of regio- and stereochemistry.
corresponding fused 2H-pyran.11 Gratifyingly, however, in
MeOH or (better) THF, complex 1 emerged, with the added
feature of complete Z stereoselectivity (Scheme 1). To probe
the potential regiochemistry of this transformation, 1-tri-
metylsilyl-1,7-octadiyne was exposed to identical conditions,
again providing only one product, 2, in which the imido group
has transferred exclusively to the substituted diene terminus.
The structures of 1 and 2 were readily assigned on the basis of
the characteristic shieldings of CpCo-complexed diene hydro-
gens,7,12 and by X-ray structural analyses of 213 and of ligands
3 and 4. The latter were obtained by oxidative demetallation of
1 and 2, respectively, using iron(III) nitrate.14w
The scope of this reaction with other amides was tested next.
Since the synthetic interest lay with the organic products, a
simple one pot procedure was executed, in which the initial
mixture was treated with solid Fe(NO3)3Á9H2O (1 equiv.) at
0 1C. The results are summarized in Table 1. With simple
amides, acetamide performed relatively poorly (entry 1), but
dienamides derived from 2-pyrrolidinone (entry 2) and
oxindole (entry 3) were isolated in 55% and 65% yield,
respectively. Similarly, with imides, diacetamide gave 8 in only
moderate yield (entry 4), but phthalimide (using the one pot
procedure) converted to 3 in 81% isolated yield (entry 5).
Dienamides are important Diels–Alder partners that have
been used for the preparation of polycyclic systems, including
natural products.1 Transition metal-mediated or -catalyzed
methods for the formation of these compounds are relatively
scarce. Thus, linear (E)-N-(1,3-butadienyl)amides have been
made by Ru-catalyzed co-oligomerization of N-vinylamides
with alkynes2 or Ti-mediated coupling of ynamides with
alkynes.3 In addition, N-(1,3-buta-2-dienyl)amides have been
synthesized via Ru-catalyzed enynamide metathesis4 or Pd-
catalyzed cross-coupling of N-vinylamides with vinyl triflates.5
Wakatsuki and Yamazaki observed that (Z5-cyclopenta-
dienyl)(triphenylphosphine)-2,3,4,5-tetraphenylcobaltacyclo-
pentadiene added thioacetanilide and two thiourea derivatives
to give the corresponding uncomplexed N-butadienamides,
although stereochemistry was not established rigorously.6
Recently, we reported that 2- and 4-pyridone react with
1,7-octadiyne and CpCo(C2H4)2 by alkyne coupling with
simultaneous N–H activation to yield 1-pyridonyl(Z4-1,3-
butadiene)cyclopentadienyl-cobalt complexes.7 These results
for Co suggested potential generality, prompting the title
studies.
To avoid competitive cobalt-catalyzed [2 + 2 + 2] oligo-
merization of the diyne,8 or [2 + 2 + 2] cooligomerization of
the diyne with ethene,9 we carried out simultaneous slow
additions of the alkyne (1 equiv.) and CpCo(C2H4)2
(1 equiv.)10 to a solution (or slurry) of the amine at room
temperature using a syringe pump. Simple amines (dimethyl-
amine, cyclopentylamine) proved inert to these conditions.
Turning to a more acidic substrate, attempted coupling of
phthalimide (5 equiv.) with 1,7-octadiyne (1 equiv.) in dry
degassed DMF or DMSO as solvents gave only complex
mixtures, while acetone compromised the diyne to give the
a Department of Chemistry, University of California at Berkeley, and
the Chemical Sciences Division, Lawrence Berkeley National
Laboratory, Berkeley, California 94720-1460, USA.
E-mail: kpcv@berkeley.edu; Fax: ++1 510 643 5208;
Tel: ++1 510 642 0286
b Laboratoire de Chimie Organique UMR 7611, Institut de Chimie
Mole´culaire FR2769, Universite´ Pierre et Marie Curie, Tour 44-54,
Paris, 4 place Jussieu 75252, France
w Electronic supplementary information (ESI) available: Experimental
details, spectral data of new compounds, computations. CCDC
reference numbers 664316 (3), 664315 (4), 664317 (10a), 664319
(14a), 664318 (21a) and 664320 (23a). For crystallographic data in
CIF or other electronic format see DOI: 10.1039/b716841a
Scheme 1 Synthesis of complexes 1–4 [1H NMR (CDCl3) d (ppm)]
and ORTEP views of 3 and 4 (30% probability ellipsoids).
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Table
1,7-octadiyne and amides
1
N-(Z)-(2-Methylenecyclohexylidene)methanamines from
Table 2 Hydroaminative coupling of substituted a,o-diynes
Entry
1
Substrate
Product
Yield (%)
24
Acetamide
2
3
4
5
6
2-Pyrrolidinone
Oxindole
55
65
32
81
69
Entry Substrate
Phthalimide
Yield (a : b : c, %)a
1
2
3
4
5
6
7
n = 1, R1 = H, R2 = SiMe3
10a : 10b : 10c = 72 : 0 : 0
11a,b : 11c = 64 : 0
4a : 4b : 4c = 66 : 0 : 0
12a : 12b : 12c = 70 : 0 : 0
13a,b : 13c = 48 : 0
14a : 14b : 14c = 62 : 18 : 0b
n = 1, R1 = R2 = SiMe3
n = 2, R1 = H, R2 = SiMe3
n = 2, R1 = H, R2 = Ph
n = 2, R1 = R2 = Ph
Diacetamide
Phthalimide
2-Oxazolidinone
n = 2, R1 = Ph, R2 = SiMe3
n = 2, R1 = H, R2 = CMe2OH 15a : 15b : 15c = 70 : 0 : 0
8
9
10
11
12
13
n = 2, R1 = R2 = CMe2OH
n = 2, R1 = H, R2 = CO2Me
n = 2, R1 = R2 = CO2Me
n = 2, R1 = H, R2 = BPinc
n = 2, R1 = R2 = BPin
16a,b : 16c = 58 : 0
Complex mixture
17a,b : 17c = 0 : 70
18a : 18b : 18c = 22 : 13 : 0
19a,b : 19c = 0 : 60
[2 + 2 + 2] Oligomers
n = 3, R1 = H, R2 = SiMe3
Oxindole
n = 2, R1 = H, R2 = SiMe3
n = 2, R1 = H, R2 = Ph
14
15
20a : 20b : 20c = 14 : 65 : 0
21a : 21b : 21c = 78d : 0 : 0
Finally, the carbamate 2-oxazolidinone transformed to 9 in
69% yield (entry 6).15 All of these compounds were obtained
as single diastereomers and their stereochemical assignment
was based on the X-ray structural analyses of 2–4, above, as
well as 10a, 12a and 14a (vide infra). Further corroboration
derived from the presence of 1H NMR NOE enhancements of
the proton signals of the amidyl bearing terminal diene posi-
tion with the neighboring cyclohexyl CH2, and the absence of
any such effects on the signals of the other alkenyl hydrogens.
Using phthalimide and oxindole as the amide partners, the
effect of varying the structure of the diyne on this process was
examined (Table 2). Interestingly, the parent 1,6-hepta- and
1,8-nonadiynes underwent [2 + 2 + 2] oligomerization
exclusively. On the other hand, while monosilylation of the
latter did not improve on this outcome (entry 13), 1-trimethyl-
silyl-1,6-heptadiyne allowed the formation of dienamide 10a
as a single isomer in 72% yield (entry 1). Its structure was
ascertained by X-ray analysis (see ESIw). Similarly, 1,7-bis-
(trimethylsilyl)-1,6-heptadiyne resulted in 11a in 64% yield
(entry 2). Further experiments focused on the 1,7-octadiyne
framework (entries 3–12). Thus, 4 emerged from the one pot
procedure in yields comparable to the stepwise sequence (entry
3). Switching from mono-SiMe3 to Ph maintained regioselec-
tivity (entry 4), and 1,8-diphenylocta-1,7-diyne converted to
13a (entry 5), albeit in lower yield. To compare the relative
directing power of these substituents, entry 6 was executed. A
mixture containing mainly 14a ensued, from which crystals
suitable for X-ray diffraction precipitated, revealing the
attachment of the heterocycle to the silylated carbon
(see ESIw). The method proved compatible with alcohols
a
Stereo- and regiochemical assignments are based on X-ray structural analyses,
b
NOE experiments and comparison of NMR chemical shifts. Not separated.
d
Pin = 2,3-dimethylbutane-2,3-dioxy. Z : E = 70 : 30.
c
(entries 7 and 8), but not with esters (entries 9 and 10). With
dimethyl deca-2,8-diynedioate (entry 10), the isolation of 17c
indicates competitive ethene interception of the intermediate
cobaltacyclopentadiene (vide infra). Switching from carbonic
to boronic esters appears promising at least for monoboro-
nates (entry 11), furnishing the novel borylated dienamides
18a and 18b, although so far inefficiently and without much
selectivity. Diboronates failed, transforming to 19c only (entry
12). An indication of the energetic closeness of the regiochem-
ical alternatives of hydroamination is provided by entry 14.
Here, oxindole, unlike phthalimide (entry 3), couples effi-
ciently with 1-trimethylsilyl-1,7-octadiyne to deliver the amide
Scheme 2 Cp transfer reactions to 22 and 24, respectively. Yields are
based on CpCo(C2H4).
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Notes and references
1 For selected examples, see: (a) E. Paredes, R. Brasca, M. Kneete-
man and P. M. E. Macini, Tetrahedron, 2007, 63, 3790; (b) J. P.
Murphy, M. Nieuwenhuyzen, K. Reynolds, P. K. S. Sarma and P.
Scheme 3 Mechanism of hydroaminative coupling.
J. Stevenson, Tetrahedron Lett., 1995, 36, 9533; (c) K. Neuschutz,
¨
J.-M. Simone, T. Thyrann and R. Neier, Helv. Chim. Acta, 2000,
83, 2712; (d) Y. Huang, T. Iwana and V. H. Rawal, Org. Lett.,
2002, 4, 1163; (e) C. A. Zezza and M. B. Smith, J. Org. Chem.,
1988, 53, 1161; (f) H. McAlonan, J. P. Murphy, M. Nieuwenhuy-
zen, K. Reynolds, P. K. S. Sarma, P. J. Stevenson and N.
Thompson, J. Chem. Soc., Perkin Trans. 1, 2002, 69.
2 H. Tsujita, Y. Ura, S. Matsuki, K. Wada, T.-a. Mitsudo and T.
Kondo, Angew. Chem., Int. Ed., 2007, 46, 5160.
group predominantly to the non-silylated side, as in 20b.
However, regiochemistry is restored when using 1-phenyloc-
ta-1,7-diyne (entry 15). This is the only case in which the
expected product (Z)-21a (structurally ascertained by X-ray
diffraction, see ESIw) has suffered (presumably acid-cata-
lyzed)7 partial isomerization into the E isomer.
3 R. Tanaka, S. Hirano, H. Urabe and F. Sato, Org. Lett., 2003, 5,
67.
Finally, very surprising involvement of the normally inert
Cp ligand8 was observed on attempted conversion of 22 and
24, respectively, with phthalimide. In the case of 22, a cyclo-
pentadienyl ligand was trapped by [2 + 2 + 2] cocyclization
to give complex 23a,16 the structure of which was confirmed by
X-ray analysis (ESI,w Scheme 2). Complex 23b arising from
ethene insertion was also isolated from the product mixture. On
the other hand, a redox reaction appears to prevail with diyne
24, the N-cyclopentadienylated 25 (mixture of double bond
isomers) formally derived by oxidative coupling of its compo-
nents, being complemented by the reductively coupled 26.
It seems likely that the mechanism of this reaction follows
that previously described using DFT computations for the
N–H activation of pyridones.17 We have expanded on these
calculations with cyclopentylamine, 2-pyrrolidinone and suc-
cinimide (see ESIw for details). To summarize (Scheme 3), a
cobaltacyclopentadiene is first formed by oxidative coupling of
the two triple bonds. It reacts with the amide to give the
corresponding N-coordinated 18-electron complex A. Proton
transfer from nitrogen to carbon occurs to give a dienylcobalt
species B, a step that has a prohibitively high barrier for
alkanamines. This intermediate rearranges subsequently into
an N-coordinated cobaltacyclopentene C. The latter reduc-
tively valence tautomerizes selectively in the opposite direction
of the amido group to give D, which accounts for the stereo-
selectivity. The regiochemistry (with the exception of that in
20b) appears to be controlled by initial proton transfer to the
least substituted (or hindered) position in the cobaltacyclo-
pentadiene.
4 M. Mori, H. Wakamatsu, N. Saito, Y. Sato, R. Narita, Y. Sato
and R. Fujita, Tetrahedron, 2006, 62, 3872.
5 K. S. A. Vallin, Q. Zhang, M. Larhed, D. P. Curran and A.
Hallberg, J. Org. Chem., 2003, 68, 6639.
6 Y. Wakatsuki and H. Yamazaki, J. Organomet. Chem., 1978, 149,
385.
7 C. Aubert, P. Betschmann, M. J. Eichberg, V. Gandon, T. J.
Heckrodt, J. Lehmann, M. Malacria, B. Masjost, E. Paredes, K. P.
C. Vollhardt and G. D. Whitener, Chem.–Eur. J., 2007, 13, 7443.
8 For general reviews of transition-metal mediated [2 + 2 + 2]
cycloadditions, see: (a) N. Agenet, O. Buisine, F. Slowinski, V.
Gandon, C. Aubert and M. Malacria, Organic Reactions, ed. T. V.
RajanBabu, John Wiley and Sons, Hoboken, 2007, vol. 68, p. 1; (b)
P. R. Chopade and J. Louie, Adv. Synth. Catal., 2006, 348, 2307;
(c) V. Gandon, C. Aubert and M. Malacria, Chem. Commun.,
2006, 2209; (d) for an early review of CpCo mediated [2+2+2]
cycloadditions, see: K. P. C. Vollhardt, Angew. Chem., Int. Ed.
Engl., 1984, 23, 539.
9 For recent examples of ethene insertions, see: (a) A. Geny, D.
´
Lebœuf, G. Rouquie, K. P. C. Vollhardt, M. Malacria, V. Gandon
and C. Aubert, Chem.–Eur. J., 2007, 13, 5408; (b) V. Gandon, D.
Lebœuf, S. Amslinger, K. P. C. Vollhardt, M. Malacria and C.
Aubert, Angew. Chem., Int. Ed., 2005, 44, 7114.
10 For the preparation of this complex, see: (a) K. Jonas, E. Deffense
and D. Habermann, Angew. Chem., Int. Ed. Engl., 1983, 22, 716;
K. Jonas, E. Deffense and D. Habermann, Angew. Chem., Suppl.,
1983, 1005; (b) J. K. Cammack, S. Jalisatgi, A. J. Matzger, A.
Negron and K. P. C. Vollhardt, J. Org. Chem., 1996, 61, 4798.
´
11 (a) D. F. Harvey, B. M. Johnson, C. S. Ung and K. P. C.
Vollhardt, Synlett, 1989, 15; (b) R. Gleiter and V. Schehlmann,
Tetrahedron Lett., 1989, 30, 2893.
12 For some illustrative examples, see: (a) B. Eaton, J. A. King, Jr and
K. P. C. Vollhardt, J. Am. Chem. Soc., 1989, 108, 1359; (b) J. A.
King, Jr and K. P. C. Vollhardt, J. Organomet. Chem., 1993, 460,
91.
13 The X-ray structural determination of 2, while proving stereo-
chemistry (see ESIw), is marred by substantial disorder and its
details are therefore not included here.
14 For the seemingly only example of an N-(E)-(2-methylenecyclo-
hexylidene)methanamine, see M. Lee, I. Ikeda, T. Kawabe, S. Mori
and K. Kanematsu, J. Org. Chem., 1996, 61, 3406.
15 Complex mixtures were obtained from trifluoroacetamide, 2-hy-
droxybenzothiazole, urea and thiourea.
16 See: T. Takahashi, Z. Song, K. Sato, Y. Kuzuba, K. Nakajima and
K.-I. Kanno, J. Am. Chem. Soc., 2007, 129, 11678.
17 C. Aubert, V. Gandon, A. Geny, T. J. Heckrodt, M. Malacria, E.
Paredes and K. P. C. Vollhardt, Chem.–Eur. J., 2007, 13, 7466.
18 Monoalkynes, such as diphenyl-, phenyl- and trimethylsilylacety-
lene led to [2 + 2 + 2] cycloadducts only. There is no catalytic
turnover of Co, even at elevated temperatures. Several other metal
systems based on Rh, Ir and Ru were ineffective.
In summary, we have discovered a simple route to diena-
mides that combines the coupling of a,o-diynes with hydro-
amination. This methodology allows the rapid chemo-, regio-
and stereoselective construction of amidated 1,2-dimethylene-
cycloalkanes. While limited to diynes and non-catalytic,18 it
gives rise to novel structures and establishes the feasibility of
the strategy. We are now evaluating the products as Diels–
Alder partners for the construction of complex molecules.
This work was supported by the NSF (CHE 0451241),
France-Berkeley Fund, CNRS, MRES and IUF. We used
extensively the computing facilities of CRIHAN, Plan Inter-
regional du Bassin Parisien (project 2006-013) and of the
´
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