Double C-H activation during functionalization of phenyl(methyl)ketene on iridium(I) using alkynes. Synthesis of 1,4-dien-3-ones

Article abstract of DOI:10.1021/ja048489+

Under the influence of an Ir(I) metal fragment, the methyl group of phenyl(methyl)ketene undergoes two C-H activations in reacting with internal alkynes, giving metallacycles 3 in 86-94% yield. Treatment of 3 with CO liberates 1,4-dien-3-ones 5 in 81-93% yield, along with CO complex 4. A possible mechanism for the very selective double C-H activation-alkyne coupling is discussed. Copyright

Full text of DOI:10.1021/ja048489+

Published on Web 07/02/2004
Double C-H Activation during Functionalization of Phenyl(methyl)ketene on
Iridium(I) Using Alkynes. Synthesis of 1,4-Dien-3-ones
Douglas B. Grotjahn,* Justin M. Hoerter, and John L. Hubbard
Department of Chemistry, San Diego State UniVersity, 5500 Campanile DriVe, San Diego, California 92182-1030,
and Department of Chemistry and Biochemistry, Utah State UniVersity, Logan, Utah 84322-0300
Received March 16, 2004; E-mail: grotjahn@chemistry.sdsu.edu
Scheme 1
Multiple C-H activation at a single carbon atom is rare,
especially on one metal center.1,2 In some cases, strongly binding
polydentate ligands are required to observe double or triple C-H
activations on a single metal.1i,j Although such multiple-activation
processes on mononuclear species lead to fascinating isomerizations
or rearrangements, in particular the formation of carbene complexes
from sp3-carbons in alkanes, there does not appear to be any use
of such activation in coupling processes,1 with concomitant C-C
bond formation.3 Organic side products occasionally isolated from
stoichiometric reactions of Fischer carbene complexes suggest that
Table 1. Syntheses of Metallacycles 3 and Dienones 5a
single C-H activation of carbene or ketene complexes and alkyne
insertion is possible.4a Here we report an efficient tandem process
yield of 3 from 2
NMR isolated
yield of 5 from 3
involving two C-H activations at the same carbon, unusual in itself
and, as far as we are aware, unique for ketene ligands or
intermediates.5
1
2
R
R
NMR
isolated
a
b
b′
c
CH3
Et
CH3
Et
Ph
CH3
CH3
CH3
Et
Et
CH3
Ph
94
49
40
96
-
78
92
78
71b
87b
66b
Phenyl(methyl)ketene complex 1 was prepared for this work in
83% yield by allowing P(i-Pr)3 and [ClIr(cyclooctene)2]2 to react
in benzene for 2 h, followed by careful addition of the ketene as a
solution.6,7 The structure of the complex, in particular its C,O-
coordination8 and the proximity of the ketene methyl substituent
to the metal fragment, are indicated by diagnostic NMR and IR
data.9 In a similar way, 2-butyne complex 2a4c was made, and its
structure is reported here.7,10 Solutions of 1 or 2a in dry and oxygen-
free C6D6 were observed to be stable at ambient temperature, though
1 showed some thermal reactivity.11 However, when phenyl-
(methyl)ketene (2.5 equiv) was added to a solution of 2a, consump-
tion of both 2a and the ketene commenced immediately. The ketene
reacted faster, perhaps because of competing polymerization. After
18 h, formation of a new Ir hydride complex 3a was complete (94%
yield by NMR, 78% after isolation). Similar results using less of
the ketene were obtained by heating ketene complex 1 and 2-butyne
at 60 °C for 18 h. In the product 3a, an Ir hydride was implicated
81
93
82
c
d
72b,c
81b
60b
d′ + d′′ c
45 + 41
a See Supporting Information for details. b Combined yield of two
stereoisomers. Full chromatographic separation not achieved. c d′′ )
diastereomer of d′ with opposite (Z) exocyclic alkene configuration. Only
small amounts of 3d were detected during the course of the reaction. See
text.
1
by a triplet in the H NMR spectrum at -22.42 ppm (1 H, J )
16.0 Hz, Ir-H coupled to two equivalent P nuclei), whereas the
conversion of 2-butyne into a 2-butenyl moiety was suggested by
resonances ascribed to a vinyl H (5.82 ppm, qq, J ) 7.0, 1.4 Hz,
1 H) and two methyl groups (1.60 ppm, d, J ) 7.0 Hz, 3 H; 1.84
ppm, narrow multiplet, 3 H). However, one resonance that was
difficult to explain was a downfield singlet at 10.70 ppm (1 H).
An X-ray diffraction study12 pointed the way to structure 3a
(Figure 1). Key features include (a) cis-coordination of hydride and
vinyl ligands, (b) geometry of the 2-butenyl substituent consistent
with insertion of 2-butyne into an Ir-H bond at some stage of the
reaction (vide infra), and (c) an unusually short Ir-C bond length.
The latter point shows that the core metallacycle of 3a can be
regarded as a metallafuran, with a significant contribution from
resonance form 3′.13 Contribution from 3′ helps explain the unusual
downfield NMR shift of both the carbon bound to Ir (δ 197.7 ppm,
assigned with aid of 2D NMR7) and its attached proton (vide
supra).
Figure 1. Molecular structure of 3a. Key bond lengths (Å) and angles (°):
Ir-O 2.193(5), C(23)-O 1.282(10), C(23)-C(22) 1.439(11), C(21)-C(22)
1.364(14), Ir-C(21) 1.955(8), P(1)-Ir-P(2) 161.6(1), Cl-Ir-O 92.6(1),
O-Ir-C(21) 76.4(3). The hydride position is assumed to be trans to oxygen.
Table 1 shows that analogues of 3 are obtained in over 86%
yield by heating 1 with a variety of internal alkynes.14 The
unsymmetrical alkyne 2-pentyne is incorporated with modest
regioselectivity, but 1-phenyl-1-propyne gave essentially one re-
giochemistry. The structures of 3 were assigned in analogy to that
of 3a, almost all proton and carbon resonances being assigned
through extensive use of gCOSY, HMQC, and gHMBC data.7
9
8866
J. AM. CHEM. SOC. 2004, 126, 8866-8867
10.1021/ja048489+ CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
CIF). This material is available free of charge via the Internet at
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Surprisingly, in the case of reactions of 1-phenyl-1-propyne or its
complex 2d, these data and careful use of NOE experiments
revealed that only traces (7% at most) of metallacycle isomer 3d
were formed. Instead, the two major products (3d′ and 3d′′, total
86% yield) shared the same regiochemistry but a different exocyclic
alkene configuration.16
References
(1) (a) Arndtsen, B. A.; Bergman, R. G. J. Organomet. Chem. 1995, 504,
143-146. (b) Kee, T. P.; Gibson, V. C.; Clegg, W. J. Organomet. Chem.
1987, 325, C14-C18. (c) Gutie´rrez-Puebla, E.; Monge, AÄ .; Carmen
Nicasio, M. C.; Pe´rez, P. J.; Poveda, M. L.; Carmona, E. Chem. Eur. J.
1998, 4, 2225-2236. (d) Slugovc, C.; Mereiter, K.; Trofimenko, S.;
Carmona, E. Angew. Chem., Int. Ed. 2000, 39, 2158-2160. (e) Slugovc,
C.; Mereiter, K.; Trofimenko, S.; Carmona, E. HelV. Chim. Acta 2001,
84, 2868-2883. (f) Lee, D.-H.; Chen, J.; Faller, J. W.; Crabtree, R. H.
Chem. Commun. 2001, 213-214. (g) Slugovc, C.; Padilla-Mart´ınez, I.;
Sirol, S.; Carmona, E. Coord. Chem. ReV. 2001, 213, 129-157. (h) Barrio,
P.; Castarlenas, R.; Esteruelas, M. A.; Onate, E. Organometallics 2001,
20, 2635-2638. (i) Gusev, D. G.; Lough, A. J. Organometallics 2002,
21, 2601-2603. (j) Kuznetsov, V. F.; Lough, A. J.; Gusev, D. G. Chem.
Commun. (Cambridge) 2002, 2432-2433.
(2) For examples on clusters, see: Rosenberg, E.; Kabir, S. E.; Hardcastle,
K. I.; Day, M.; Wolf, E. Organometallics 1990, 9, 2214-2217. Adams,
R. D.; Babin, J. E.; Kim, H. S. J. Am. Chem. Soc. 1987, 109, 1414-
1424. Cifuentes, M. P.; Jeynes, T. P.; Gray, M.; Humphrey, M. G.; Skelton,
B. W.; White, A. H. J. Organomet. Chem. 1995, 494, 267-272.
(3) For leading references to single C-H activation followed by alkene or
alkyne insertion, see: Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. ReV. 2002,
102, 1731-1770. Lail, M.; Arrowood, B. N.; Gunnoe, T. B. J. Am. Chem.
Soc. 2003, 125, 7506-7507.
(4) (a) See work cited in footnote 5 of ref 4b. For a more recent leading
reference, see: Rudler, H.; Parlier, A.; Bezennine-Lafollee, S.; Vaisser-
mann, J. Eur. J. Org. Chem. 1999, 2825-2833. (b) Grotjahn, D. B.; Lo,
H. C. J. Am. Chem. Soc. 1996, 118, 2097-2098. (c) Lo, H. C.; Grotjahn,
D. B. J. Am. Chem. Soc. 1997, 119, 2958-2959.
(5) Geoffroy, G. L.; Bassler, S. L. AdV. Organomet. Chem. 1988, 28, 1-83.
Tidwell, T. T. Ketenes; Wiley: New York, 1995.
(6) If the ketene was added neat, or if there was excess phosphine or metal
precursor, lower yields of ketene complex were obtained; observation of
insoluble white opaque material suggested that the ketene had polymerized.
(7) See Supporting Information for full details.
Demetalation of 3 could be effected by heating solutions under
1
a CO atmosphere at 60-80 °C for 1-2 d. As monitored by H
NMR spectroscopy and careful integrations, the metal-containing
product was 4, whereas the organic species was dienone 5 (81-
93% yield before isolation, Table 1). Intermediates were not
detected in these reactions, but it would be reasonable to assume
formation of 4 and 5 by ligand exchange of CO for carbonyl
oxygen, followed by reductive elimination.
Several observations help explain the course of the double C-H
activation. We previously characterized the first ketene-alkyne
complexes, which could be generated either from the diphenylketene
complex related to 1 and 2-butyne at 60 °C or from 2-butyne
complex 2a and diphenylketene at room temperature, both ex-
changes occurring with loss of one phosphine.4c The formation of
3 from either 1 or 2 follows similar behavior (lower reaction
temperature starting from the alkyne complex), except that we could
not detect an intermediate. Thus, we propose that a ketene-alkyne
complex (not shown) is formed, which unlike the diphenylketene
case rapidly undergoes initial C-H activation at the ketene methyl
carbon, forming A.15 Because we do not see intermediates in these
(8) Grotjahn, D. B.; Collins, L. S. B.; Wolpert, M.; Lo, H. C.; Bikzhanova,
G. A.; Combs, D.; Hubbard, J. L. J. Am. Chem. Soc. 2001, 123, 8260-
8270.
(9) Grotjahn, D. B.; Lo, H. C. Organometallics 1995, 14, 5463-5465, footnote
16.
(10) Crystal data for 2a: triclinic, P1h (No. 2), orange block, 0.35 × 0.35 ×
0.60 mm, a ) 9.415(3) Å, b ) 9.858(3) Å, c ) 14.708(4) Å, R )
79.67(3)°, â ) 83.31(3)°, γ ) 77.89(8)°, V ) 1308.7 (8) Å3, Z ) 2, T )
173 K, Dcalc ) 1.528 mg/m3, wR ) 9.36% for 5687 observed reflections,
wR ) 9.60% for 6037 independent reflections, GOF ) 1.079.
(11) Heating 1 in the absence of alkyne at 85 °C for 6 d in dry and oxygen-
free C6D6 produced CO complex 4 and styrene (each g98% yield).
(12) Crystal data for 3a: monoclinic, P21/n, orange prism, 0.4 × 0.5 × 0.6
mm, a ) 10.028(1) Å, b ) 15.732(2) Å, c ) 21.362(2) Å, â )
98.543(9)°, V ) 3332.7(6) Å3, Z ) 4, T ) 298 K, Dcalc ) 1.49 g/cm3, wR
) 9.85% for 5853 observed reflections, wR ) 22.25% for 5887
independent reflections, GOF ) 1.039.
(13) Similar unusual bond lengths have been noted in other, related species.
See, for example: Bleeke, J. R.; New, P. R.; Blanchard, J. M. B.; Haile,
T.; Beatty, A. M. Organometallics 1995, 14, 5127-5137 and ref 6 therein.
(14) Not surprisingly, the small amount of 1 which did not react with the alkyne
was converted to 4.11 Terminal alkynes led to formation of vinylidene
complexes, without incorporation of the ketene. 1-Trimethylsilyl-1-propyne
produced small amounts (ca. 5%) of 3 of undetermined regiochemistry,
but most alkyne was converted to the vinylidene complex trans-[Me3Si-
(Me)CC]Ir(Cl)[P(i-Pr)3]2.4c
reactions, the metal center is identified simply as [Ir]. Subsequent
alkyne insertion on A would give a vinyl ligand in B. Reductive
elimination on B, perhaps favored by the availability of an extensive
π-system, could produce dienone π-complex C or an isomer thereof.
Finally, C-H activation on C would lead to 3.17 According to this
proposal, the double C-H activation may occur at two different
stages in the alkyne incorporation process, but other variants are
conceivable.
In summary, we show that a single metal center in 1 is able to
activate a ketene substituent twice under mild conditions, and in a
way which allows efficient C-C bond formation with alkynes. The
resulting metallacycles 3 afford dienones 5 in good yields. There
are few examples of dienones related to 5, yet similar dienones
undergo useful Lewis acid-promoted cyclizations.18 The role of
multiple activation processes in tandem with insertion and C-C
coupling processes in forming new organometallic and organic
products is a subject of continuing investigation.
(15) We previously reported the photochemical activation of the methyl group
in 1, which leads to a hydride related to A but lacking the alkyne. See
footnote 26 of ref 4b.
(16) The ratio of these products changed somewhat over time,7 in a reaction
which was slightly accelerated by addition of 2-phenylpropionic acid, a
likely product of hydrolysis of some phenyl(methyl)ketene. Thus, the most
likely isomerization mechanism involves proton catalysis, though see
also: Huggins, J. M.; Bergman, R. G. J. Am. Chem. Soc. 1979, 101, 4410-
4412. Alexander, J. J. In The Chemistry of the Metal-Carbon Bond, Vol.
2; Hartley, F., Patai, S., Eds.; Wiley: New York, 1985; pp 339-400.
(17) An example of dienone metalation: Tully, W.; Main, L.; Nicholson, B.
K. J. Organomet. Chem., 2001, 633, 162-172.
Acknowledgment. Galina Bikzhanova is thanked for performing
initial experiments. The NSF and PRF, administered by the
American Chemical Society, are thanked for generous support of
this and related work.
(18) Examples: Kjeldsen, G.; Knudsen, J. S.; Ravn-Petersen, L. S.; Torssell,
K. B. G. Tetrahedron, 1983, 39, 2237-2239. Giese, S.; West, F. G.
Tetrahedron Lett. 1998, 39, 8393-8396. Wang, Y.; Schill, B. D.; Arif,
A. M.; West, F. G. Org. Lett. 2003, 5, 2747-2750.
Supporting Information Available: Details of the synthesis and
characterization of products and crystal structures of 2a and 3a (PDF,
JA048489+
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