Aldehyde addition to 1,3-butadiyne-derived zirconacyclocumulenes: Stereoselective synthesis of cis-[3]cumulenols

Article abstract of DOI:10.1021/om100287d

The direct addition of aldehydes to zirconacyclocumulenes generated through the coupling reactions of benzynezirconocenes with 1,3-butadiynes is achieved cleanly under controlled reaction conditions, which provids a highly stereoselective method for the synthesis of tetra-substituted [3]cumulenols. DFT calculations suggest that there is an equilibrium between seven-membered zirconacyclocumulene (3) and the less stable but more reactive five-membered α-alkynylzirconaindene (2) in the process. The aldehyde reacts with the five-membered zirconaindene intermediate through a cyclic S_E2' pathway to afford cumulenol products after hydrolysis.

Full text of DOI:10.1021/om100287d

3012 Organometallics 2010, 29, 3012–3018
DOI: 10.1021/om100287d
Aldehyde Addition to 1,3-Butadiyne-Derived Zirconacyclocumulenes:
Stereoselective Synthesis of cis-[3]Cumulenols
Xiaoping Fu, Yuanhong Liu,* and Yuxue Li*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, People’s Republic of China
Received April 9, 2010
The direct addition of aldehydes to zirconacyclocumulenes generated through the coupling
reactions of benzynezirconocenes with 1,3-butadiynes is achieved cleanly under controlled reaction
conditions, which provids a highly stereoselective method for the synthesis of tetra-substituted
[3]cumulenols. DFT calculations suggest that there is an equilibrium between seven-membered
zirconacyclocumulene (3) and the less stable but more reactive five-membered R-alkynylzirconain-
dene (2) in the process. The aldehyde reacts with the five-membered zirconaindene intermediate
through a cyclic SE20 pathway to afford cumulenol products after hydrolysis.
Introduction
1,3-butadiynes.2 The chemistry of 1,3-butadiynes R(CtC)2R
and polyynes R(CtC)nR with group 4 metallocenes3-5 has
been extensively studied by Rosenthal et al.3 using the metal-
locene sources Cp2M(L)(η2-Me3SiCtCSiMe3) (M = Ti,
L=-; M=Zr, L= THF) as low-valent metal equivalents.
The successful isolation of highly reactive metal species with
fascinating structural features well accelerated the develop-
ment in this area. For example, it was demonstrated that
zirconacycles with a cumulenic structure could be formed
during the coupling process.3,5b Takahashi et al. reported that
the reaction of 1,3-butadiynes with a zirconocene-ethylene
complex afforded cis-enynes after hydrolysis and R-alkynyl-
cyclopentenones by treatment with CO/I2.4a,b Meunier and
co-workers studied the coupling of benzynezirconocene with
1,4-diphenyl-1,3-butadiyne6a and 1,4-bis(trimethylsilyl)-1,3-
butadiyne.6b In both cases a benzo-fused seven-membered
zirconacyclocumulene could be isolated, although in the latter
case, a β-alkynylzirconaindene was also isolated as a minor
complex. Theoretical calculations revealed that an interaction
of the d metal atomic orbital with one terminal σ orbital and
with the in-plane π orbital of the cumulene contribute to the
remarkable stability of these metal complexes.6a Recently, we
Zirconacycles, which are easily prepared by reductive cou-
pling of unsaturated compounds such as alkynes, alkenes,
nitriles, aldehydes, or ketones on a low-valent zirconocene
equivalent, have attracted a lot of attention due to their versa-
tile utility in organometallic and organic synthesis.1 For seve-
ral years, our group has been interested in the development of
new synthetic strategies based on zirconocene coupling of
*Corresponding authors. E-mail: yhliu@mail.sioc.ac.cn.
(1) For reviews, see: (a) , Q.; Lu, J.; HuWang, C.; Wang, C.; Xi, Z.
Tetrahedron 2007, 63, 6614. (b) Titanium and Zirconium in Organic
Synthesis, Marek, I., Ed.; Wiley-VCH: Weinheim, Germany, 2002. (c)
Negishi, E.; Takahashi, T. In Organometallic Complexes of Zirconium
and Hafnium, Science of Synthesis (Houben-Weyl Methods of Molecular
Transformations); Imamoto, T., Ed.; Georg Thieme Verlag: Germany, 2003;
pp 681-848. (d) Takahashi, T.; Xi, Z.; Hara, R. Trends Organomet. Chem.
1997, 2, 117. (e) Rosenthal, U.; Burlakov, V. V.; Arndt, P.; Baumann, W.;
Spannenberg, A. Organometallics 2005, 24, 456. (f) Xi, Z.; Li, Z. Top.
Organomet. Chem. 2004, 8, 27. (g) Buchwald, S. L. Science 1993, 261.
(h) Kotora, M.; Xi, Z.; Takahashi, T. J. Synth. Org. Chem. Jpn. 1997, 55,
958. (i) Negishi, E.; Takahashi, T. Bull. Chem. Soc. Jpn. 1998, 71, 755.
(j) Takahashi, T.; Xi, Z.; Kotora, M. Pure Appl. Chem. 1998, 2, 515. (k)
Takahashi, T.; Kotora, M.; Hara, R.; Xi, Z. Bull. Chem. Soc. Jpn. 1999, 72,
2591.
(2) (a) Fu, X.; Chen, J.; Li, G.; Liu, Y. Angew. Chem., Int. Ed. 2009,
48, 5500. (b) Chen, J.; Li, Y.; Gao, H.; Liu, Y. Organometallics 2008, 27,
5619. (c) Liu, Y.; Gao, H. Org. Lett. 2006, 8, 309. (d) Liu, Y.; Gao, H.; Zhou,
S. Angew. Chem., Int. Ed. 2006, 45, 4163. For titanation of conjugated 1,3-
butadiynes and their coupling reactions with aldehydes, see: (e) Chen, J.;
Liu, Y. Tetrahedron Lett. 2008, 49, 6655. For titanium-mediated trisub-
stituted cis-[3]cumulenols formation, see: (f) Chen, J.; Liu, Y. Organo-
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(3) For reviews, see: (a) Rosenthal, U.; Burlakov, V. V.; Arndt, P.;
Baumann, W.; Spannenberg, A. Organometallics 2005, 24, 456, and
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W.; Spannenberg, A. Organometallics 2003, 22, 884. (c) Rosenthal, U.
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pubs.acs.org/Organometallics
Published on Web 06/04/2010
2010 American Chemical Society

Article
Organometallics, Vol. 29, No. 13, 2010 3013
Scheme 1
have shown that zirconocene-ethylene-mediated coupling of
1,3-butadiynes with aldehydes or ketones provides an effi-
cient, general, andone-potmethodforcis-[3]cumulenols.2d We
suggested that the zirconacyclocumulenic intermediates were
involved in our reactions.2b We also found the diverse reactivity
of zirconacyclocumulenes derived by coupling of benzynezir-
conocenes with 1,3-butadiynes toward different cyanide com-
pounds such as carbamoyl cyanides or aroyl cyanides, leading
to indeno[2,1-b]pyrroles and [3]cumulenones, respectively.2a
We also developed a titanium-mediated cis-[3]cumulenol for-
mation in the presence of Lewis acid.2f These results prompted
us to examine the reaction with aldehydes. In this paper, we
report a direct addition of aldehydes to zirconacyclocumulenes
3, which affords an efficient access to synthetically useful
[3]cumulenols with high regio- and stereoselectivity (Scheme 1).
We also report the mechanistic insights into this unusual
transformation based on DFT calculations.
Table 1. Hydrolysis of Zirconacyclocumulene Complexes
Results and Discussion
Hydrolysis of Zirconacyclocumulene Complexes 3 Gener-
ated through Coupling of Benzynezirconocene with 1,3-Buta-
diynes. Zirconocene-aryne complexes, which are easily
formed by thermal decomposition of diarylzirconocene deri-
vatives, have been proved to be very useful for the synthesis
of a wide range of organic compounds through coupling
reactions with unsaturated substrates.7 It was known that the
coupling reaction of 1,4-diphenyl-1,3-butadiyne (1a) with
benzynezirconocene Cp2Zr(η2-C6H4) occurs by heating 1a
with diphenylzirconocene at 80 °C for several hours, furnish-
ing a seven-membered zirconacyclocumulene 3a (Scheme
of Table 1, R1=R2=Ph).6a It was suggested that 3a might
be formed through rearrangement of five-membered R-
alkynylzirconaindene (2a).6b Here we found that quenching
the reaction mixture with 3 N HCl for 5 min gave rise to 1,10,4-
triphenylbut-3-en-1-yne (4a) in 87% yield, but not cumulene
product (Table 1, entry 1).8 The 13C NMR clearly shows two
singlets at 89.19 and 93.65 ppm, which are typical for an
alkyne unit. Quenching the reaction mixture with 2.2 equiv of
MeOH afforded the same product (4a) in 76% yield. When
1,4-bis(4-methoxyphenyl)buta-1,3-diyne (1b) was employed,
a Isolated yields. b The reaction mixture was quenched for 30 min.
(Z)-enyne 4b was isolated in 82% yield (entry 2).9 The
Z-configuration of the enyne double bond in 4b was deter-
mined by the 2D NOESY spectrum. Bisalkyl-substituted
butadiynes including those bearing alkoxyl functional
groups underwent similar coupling reactions to produce
the corresponding (E)- or (Z)-enynes in 72-82% yields after
hydrolysis (entries 3-5). When unsymmetrically substituted
butadiynes 1f and 1g were employed, regioselective coupling
reactions were observed. The corresponding enynes 4f and 4g
were obtained as major products in 68% and 73% yield,
respectively (entries 6, 7). The structures of 4f and 4g have
been confirmed by the 2D NOESY spectrum. The above
reactions by simply quenching the zirconium intermediates
also provided an efficient method for the stereoselective
synthesis of enynes.
(7) (a) Buchwald, S. L.; Nielsen, R. B. Chem. Rev. 1988, 88, 1047. (b)
Wang, C.; Deng, L.; Yan, J.; Wang, H.; Luo, Q.; Zhang, W.; Xi, Z. Chem.
Commun. 2009, 4414. (c) Chen, C.; Xi, C.; Liu, Y.; Hong, X. J. Org. Chem.
2006, 71, 5373. (d) Zhao, C.; Li, P.; Cao, X.; Xi, Z. Chem.;Eur. J. 2002, 8,
4292.
(8) The NMR data of 4a are consistent with those reported by
Meunier; however, they proposed that the structure of 4a is 1,104-
triphenylbuta-1,2,3-triene. According to NMR spectra of 4a and 2D
NMR spectra of 4b (HMQC, HMBC, NOESY) and 4c (NOESY), 4a
should be an enyne derivative.
(9) In this case, an intermediate was observed upon quenching the
mixture in a short time, which could convert to the enyne product during
the hydrolysis process. This intermediate was difficult to isolate in pure
form due to its instability.
Reaction of Zirconacyclocumulenes with Aldehydes: For-
mation of [3]Cumulenols. Next, we proceeded to investigate

3014 Organometallics, Vol. 29, No. 13, 2010
Table 2. Formation of [3]Cumulenols via the Reaction with Aldehydes
Fu et al.
a Isolated yields. Unless noted, all the reactions were carried out using 1 equiv of aldehyde at room temperature for 1-3 h. b Room temperature, 3 h,
then 50 °C, overnight. c1.5 equiv of formaldehyde was used. d 50 °C, 3 h, and 1.2 equiv of ethyl glyoxalate was used. e 50 °C, 2 h, and 2.0 equiv of aldehyde
was used.
the reactions of zirconacyclocumulenes with aldehydes. Here
we found that treatment of the reaction mixture of 3a (R1 =
R2 = Ph) with 1.0 equiv of PhCHO at room temperature for
3 h afforded [3]cumulenol 5a smoothly in 83% yield after
hydrolysis (Table 2, entry 1). It is noteworthy that the
reaction occurred exclusively at the cumulenic zirconium
moiety, whereas the products derived from insertion of a
carbonyl group into a Zr-C(sp2) bond adjacent to the fused
benzene ring was not detected. The result suggests that this
step is highly regioselective. The behavior of zirconacyclo-
cumulene 3 toward aldehyde addition is similar to that of
R-alkynylzirconacyclopentenes/zirconacycloheptatrienes, as

Article
Organometallics, Vol. 29, No. 13, 2010 3015
˚
Figure 1. X-ray crystal structure of 5n. Selected bond lengths (A) and bond angles (deg): C1-C2 = 1.489(7), C2-C3 = 1.315(7),
C3-C4 = 1.271(7), C4-C5 1.348(7), C5-C14 = 1.481(7), C3-C2-C1 = 123.6(5), C3-C2-C7 = 119.3(5), C4-C5-C6 = 120.5(5),
C4-C5-C14 = 120.7(5).
we reported recently.2e It should be noted that zirconacycles
such as zirconacyclopentadienes and zirconaindenes are
generally not reactive toward carbon electrophiles, possibly
due to the steric hindrance caused by the bulky cyclopenta-
dienyl ligands and the occupied coordination sites around
the metal.10 To achieve C-C bond formation, it always
needs transmetalation of the zirconium-carbon bond to
another metal-carbon bond such as Cu, Zn, Li, and Ni to
increase the reactivity and achieve higher yields.11 In our
reaction, however, no transmetalation reagents are required,
which indicates that zirconacyclocumulenes are more reac-
tive than normal zirconacycles. The present method could be
applied successfully to various types of 1,3-butadiynes and
aldehydes to provide the cumulenols 5 in 46-88% yields
(Table 2). Aromatic aldehydes bearing electron-withdrawing
(-Cl) or electron-donating (-OMe) substituents had no
large influence on the product yields, and the desired cumu-
lenols 5b and 5c were isolated in 82% and 85% yield, res-
pectively (entries 2, 3). Bulky substrates, such as 2-bromo-
benzaldehyde or 1-naphthaldehyde, also smoothly afforded the
corresponding products 5d and 5e in good yields (entries 4, 5).
Interestingly, the use of 4-(phenylethynyl)phenyl alde-
hyde or alkynyl aldehyde afforded 5f and 5g in the same
yields of 81%, in which the alkyne functionality remained
intact (entries 6, 7). The use of formaldehyde gave the
corresponding primary alcohol 5h in 77% yield (entry 8).
Alkyl aldehyde, such as butyraldehyde, was also compatible
in this reaction, leading to 5i in 75% yield (entry 9). The ester
group could also be easily introduced into the alcoholic
position of cumulenol 5j (entry 10). When butadiynes bear-
ing a substituted aryl ring or alkyl-substituted butadiynes
were employed, stereoselective formation of cumulenols was
observed. In all of these cases, only cis-cumulenols were
obtained in 46-75% yields (entries 11-15). When trimethyl-
(octa-1,3-diynyl)silane (1g) was employed, no reaction was
observed with p-chlorobenzaldehyde. The cis-configura-
tion of cumulenols was confirmed by X-ray crystallographic
analysis of 5n (Figure 1). However, no reaction occurred of
zirconacycle 3a with ketone such as acetophenone. [3]Cumu-
lenes are important substances since they have potential
applications in antitumor drug design and as advanced
materials, as well as in organic synthesis.12 However, the
stereoselective synthesis of cumulenes with reasonable gen-
erality is still rare.13,14 Our method provides an efficient
and one-pot procedure for the stereoselective synthesis of
cumulenes with multifunctionalities. These cumulene deri-
vatives should be attractive substrates for further synthetic
manipulations.
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Takahashi, T. Aldrichim. Acta 1985, 18, 31.
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1999, 121, 1094.

3016 Organometallics, Vol. 29, No. 13, 2010
Fu et al.
Figure 2. Optimized five-membered structure 2a, the seven-membered structure 3a, and their isomerization transition state TS-2a-3a.
The relative free energies including solvent effect, ΔGsol(298 K), are in kcal/mol (calculated at the B3LYP/6-311þG** level).
DFT Calculations and Mechanistic Aspects. To understand
the regioselectivity in the reaction of zirconacycle 2/3 (R1=R2=
Ph) with aldehyde, density functional theory (DFT)15 studies
have been performed with the GAUSSIAN03 program16 using
the B3LYP17 method. For C, H, and O, the 6-311þG** basis set
was used; for Zr the Lanl2DZ basis set with effective core poten-
tial (ECP)18 was used. For each optimized structure, harmonic
vibrational frequency calculations were carried out and thermal
corrections were made. All structures were shown to be either
transition states (with one imaginary frequency) or local minima
(with no imaginary frequency). The solvent effect was estimated
with the IEFPCM19 (UAHF atomic radii) method in toluene
(ε = 2.379) using the gas-phase-optimized structures.
Structure of 2a and 3a. First, two possible isomers of the
zirconacycle intermediate, 2a and 3a, have been fully opti-
mized (Figure 2). The results indicate that the seven-mem-
bered structure 3a is -1.7 kcal/mol more stable than the five-
membered structure 2a. Therefore, 3a should be dominant
under room temperature. The transition state of the isomer-
ization from 2a to 3a has also been located (TS-2a-3a). The
isomerization barrier is only 4.1 kcal/mol. The low barrier of
this isomerization indicates that the seven-membered zirco-
nacyclocumulene may be formed via the five-membered
zirconacyclic intermediate.20,6b
Both experimental and theoretical studies of the seven-
membered zirconacyclocumulenes have been reported.20,5b,6
The stability of the seven-membered zirconacyclocumulene has
been ascribed to the interaction between one of the Zr d orbitals
with one terminal σ orbital and the in-plane π orbital of the
cumulene.6a The molecule orbital analysis shown in Figure 3
is consistent with this conclusion (Figure 3, HOMO-2). In
HOMO-4, the Zr dz2 orbital overlaps with the sp2-hybridized
orbital of C1, forming the Zr-C1σ covalent bond.
Origin of the Regioselectivity. The transition states for the
insertion of aldehyde into the zirconacycle have been ex-
plored first with the seven-membered structure 3a since it is
more stable than 2a. In the calculation, as the aldehyde
becomes close to C6, the seven-membered ring 3a will
convert to the five-membered ring 2a before reaching the
insertion transition state. This result is also confirmed by the
relaxed potential energy surface (PES) scan along the Zr-O
(15) (a) Hohenberg., P.; Kohn, W. Phys. Rev. 1964, 136, B864. (b)
Kohn, W.; Sham, L. J. Phys. Rev. 1965, 140, A1133.
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Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson,
G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.;
Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Frisch,
M. J.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross,
J. B.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev,
O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.;
Morokuma, K.; Voth, G. A.; Salvador, P.; Dannengerg, J. J.; Zakr-
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Article
Organometallics, Vol. 29, No. 13, 2010 3017
Figure 3. HOMO-2 and HOMO-4 molecular orbitals of 3a (depicted using isodensity at 0.04 au). HOMO-2 is involved in the
interaction of C4, C6, and the Zr center. HOMO-4 shows that the C1-Zr σ bond is formed by the overlap of the Zr dz2 orbital with the
C1 sp2-hybridized orbital.
Figure 4. Insertion of aldehyde from the left side (Path 1) and the right side (Path 2) of the zirconacycle 2a. TS1 and TS2: The optimized
transition states for the insertion reaction. The relative free energies including solvent effect, ΔGsol(298 K), are in kcal/mol (calculated at
the B3LYP/6-311þG**/Lanl2DZ level).
and C7-C6 bonds (see the Supporting Information for
detail). In 3a, the Zr center is buried deeply; C1 and C6 are
shielded more tightly. Therefore the attack of the aldehyde
will encounter large steric hindrance. Thus, the five-mem-
bered ring is less stable and has higher reactivity. The former
calculation shows that the seven-membered ring and the five-
membered ring are easy to convert to each other. Therefore,
as shown in Figure 4, the insertion reaction was studied on
the basis of the complex of the five-membered structure 2a
and the aldehyde PhCHO (R).

3018 Organometallics, Vol. 29, No. 13, 2010
Fu et al.
Scheme 2
The calculation results show that Path 2 is more favorable;
its activation barrier is lower than that of Path 1 by 11.9 kcal/
mol. This result is consistent with the experimental observa-
tions. Apparently, if the aldehyde inserts into the Zr-C4
bond, a large steric interaction will be encountered with the
alkynyl group. We propose that the steric factor is important
to the preference of TS2. As shown in Figure 4, the alkynyl
group is sticking out; the attack of C7 to C6 causes only little
steric energy. In contrast, in TS1 the aldehyde pushes the Cp
rings aside since the Zr-C1 bond is partially shielded by the
two Cp rings. In addition, as compared with TS1, the oxygen
atom in TS2 coordinated with the Zr center with a shorter
room temperature, quenched with 3 N HCl solution (usually 5
min), and extracted with diethyl ether. The extract was washed
separately with saturated NaHCO3 solution, water, and brine
and dried over anhydrous Na2SO4. The solvent was evaporated
in vacuo, and the residue was purified by column chromatog-
raphy on silica gel to afford the desired enyne products 4.
(Z)-4,40-(1-Phenylbut-1-en-3-yne-1,4-diyl)bis(methoxybenzene)
(4b). Column chromatography on silica gel (petroleum ether/
ethyl acetate = 20:1) afforded the title compound as a yellow
foam in 82% yield. 1H NMR (400 MHz, CDCl3): δ 3.74 (s, 3H),
3.81(s, 3H), 6.11 (s, 1H), 6.79 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 9.2
Hz, 2H), 7.25-7.32 (m, 7H), 7.52 (d, J = 8.8 Hz, 2H). 13C NMR
(100 MHz, CDCl3): δ 55.10, 55.13, 88.19, 93.34, 106.24, 112.98,
113.85, 115.78, 128.03, 128.10, 128.14, 131.50, 131.56, 132.71,
141.91, 151.14, 159.31, 159.34. IR (neat): 3010, 2964, 2838, 2552,
2202, 2035, 1881, 1718, 1603, 1584, 1574, 1505, 1464, 1442, 1360,
˚
distance (2.182 vs 2.272 A) and a better angle (the lone pair of
the O atom pointing to the Zr center). The product P1, which
is not obtained in the experiment, is more stable than the
product P2, so this reaction is kinetically controlled. The
structure of TS2 indicates that to form a trans product is
impossible; therefore, the cis product should be dominant.
Considering the experimental data and DFT calculations
disclosed above, a possible reaction mechanism for the synthesis
of cumulenols is outlined in Scheme 2: First of all, a fast equili-
brium between seven-membered zirconacycle 3 and five-mem-
bered zirconacycle 2 exists in the reaction mixture, in which 3 is
more stable, whereas 2 is more reactive. The addition of a carbo-
nyl group to the propargyl zirconium moiety in 2 proceeds to
generate a nine-membered oxazirconacycle 7 via a cyclic syn-
SE20 process,21 and hydrolysis of 7affords the cumulenol 5. Thus
the reaction equilibrium is shifted toward the products.
1244, 1172, 1148, 1105, 1028, 828, 801, 761, 737, 693 cm-1
HRMS (EI): calcd for C24H20O2 340.1463, found 340.1461.
.
Typical Procedure for the Addition Reaction of Aldehydes to
Zirconacyclocumulenes. To a suspension of Cp2ZrCl2 (0.19 g,
0.65 mmol) in toluene (5 mL) in a 20 mL Schlenk tube at 0 °C was
added dropwise PhLi (1.4 mmol, 2.0 M in dibutyl ether, 0.7 mL)
with a syringe. After stirring for 1 h at the same temperature, diyne 1
(0.5 mmol) was added, and the reaction mixture was heated to
80 °C and stirred for 6 h. The resulting orange-yellow solution was
allowed to return to room temperature, and aldehyde (0.5 mmol)
was added. Then the mixture was stirred at room temperature or
50 °C in some cases until the reaction was complete, as monitored
by thin-layer chromatography. The reaction mixture was allowed
to return to room temperature, quenched with 1 N HCl solution
(usually 5 min), and extracted with diethyl ether. The extract was
washed separately with saturated NaHCO3 solution, water, and
brine and dried over anhydrous Na2SO4. The solvent was evapo-
rated in vacuo, and the residue was purified by column chroma-
tography on Al2O3 or silica gel or by recrystallization to afford the
desired cumulenol products 5.
Conclusion
In summary, we have developed an efficient and convenient
method for the stereoselective synthesis of tetra-substituted
cis-[3]cumulenols through the reactions of aldehydes with
zirconacyclocumulenes. An equilibrium between seven-mem-
bered zirconacyclocumulene and five-membered R-alkynylzir-
conaindene is suggesed to exist during the process. The addition
of aldehyde to the more reactive zirconaindene intermediate
through a cyclic SE20 pathway leads to cumulenol products
after hydrolysis. We are currently exploring the new synthetic
potential of zirconacycles with cumulenic structures.
1,2,5,5-Tetraphenylpenta-2,3,4-trien-1-ol (5a). Column chro-
matography on Al2O3 (petroleum ether/ethyl acetate=10:1 to ethyl
acetate) afforded the title compound as a yellow foam in 83% yield.
1H NMR (300 MHz, CDCl3): δ 2.83 (bs, 1H), 5.92 (s, 1H), 7.12-
7.56 (m, 20H). 13C NMR (75.5 MHz, CDCl3): δ 73.44, 123.34,
123.88, 126.98, 127.37, 127.61, 127.66, 128.15, 128.34, 128.44,
128.87, 129.46, 136.89, 137.69, 138.42, 142.06, 151.66, 155.87. IR
(neat): 3419, 3057, 3028, 1597, 1490, 1443, 1278, 769, 693 cm-1
.
HRMS (EI): calcd for C29H22O 386.1671, found 386.1666.
Experimental Section
Acknowledgment. We thank the National Natural
Science Foundation of China (Grant Nos. 20732008,
20821002, 20702059), Chinese Academy of Science, Science
and Technology Commission of Shanghai Municipality
(Grant No. 08QH14030), and the Major State Basic Re-
search Development Program (Grant No. 2006CB806105)
for financial support.
Typical Procedure for the Cross-Coupling Reaction of the
Zirconocene-Benzyne Complex with Butadiynes. To a suspension
of Cp2ZrCl2 (0.19 g, 0.65 mmol) in toluene (5 mL) in a 20 mL
Schlenk tube at 0 °C was added dropwise PhLi (1.4 mmol, 2.0 M
in dibutyl ether, 0.7 mL) with a syringe. After stirring for 1 h at
the same temperature, diyne 1 (0.5 mmol) was added, and the
reaction mixture was heated to 80 °C and stirred for 6 h until GC
or TLC indicated that the starting material had been consumed.
The resulting orange-yellow solution was allowed to return to
Supporting Information Available: Experimental details,
NMR spectra of all new products, and CIF files giving crystal-
lographic data of compound 5n, the relaxed potential energy
surface (PES) scan, calculated total energies, and geometrical
coordinates. This material is available free of charge via the
Internet at http://pubs.acs.org.
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