1,3-steric induction in intermolecular radical reactions mediated by a Co2(CO)6-metal core

Article abstract of DOI:10.1021/om100472y

Diastereoselectivity of propargyl coupling reactions can be controlled by using the bulkiness of a γ-substituent as a stereochemical tool. This 1,3-steric induction was observed with γ-t-Bu and γ-Me₃Si groups, both favoring a d,l-configuration of the head-to-head coupling products, 3,4-disubstituted 1,5-alkadiynes (d,l-95-100%). X-ray crystallography analysis suggests that the most favorable orientation of converging propargyl radicals is the one in which the bulky γ-substituents are positioned anti to each other. Overall, the synthetic strategy of employing a Me₃Si auxiliary group involves five steps and affords, with 28-33% overall yields, pure d,l-3,4-diaryl-1,5-hexadiynes, otherwise hardly accessible.

Full text of DOI:10.1021/om100472y

3556 Organometallics 2010, 29, 3556–3562
DOI: 10.1021/om100472y
1,3-Steric Induction in Intermolecular Radical Reactions Mediated
by a Co2(CO)6-Metal Core
Gagik G. Melikyan,* Ryan Spencer, and Aaron Rowe
Department of Chemistry and Biochemistry, California State University Northridge,
Northridge, California 91330
Received May 14, 2010
Diastereoselectivity of propargyl coupling reactions can be controlled by using the bulkiness of a
γ-substituent as a stereochemical tool. This 1,3-steric induction was observed with γ-t-Bu and γ-Me3Si
groups, both favoring a d,l-configuration of the head-to-head coupling products, 3,4-disubstituted
1,5-alkadiynes (d,l- 95-100%). X-ray crystallography analysis suggests that the most favorable orienta-
tion of converging propargyl radicals is the one in which the bulky γ-substituents are positioned anti to
each other. Overall, the synthetic strategy of employing a Me3Si auxiliary group involves five steps and
affords, with 28-33% overall yields, pure d,l-3,4-diaryl-1,5-hexadiynes, otherwise hardly accessible.
Introduction
CF3, respectively).2c In addition, metal-promoted dimeriza-
tions exhibit a low regioselectivity because of the formation
of isomeric allene-ynes.2d Coordination of triple bonds with
transition metals has proven to be an effective strategy in stabi-
lizing propargyl cations, such as 1 (Figure 1).3 Most impor-
tantly, the formation of a π-bond between the triple bond and
transition metal precludes an unwanted acetylene-allene
rearrangement2 and directs incoming electrophiles, or radicals,
exclusively toward the R-carbon atom. The bent geometry of
the acetylenic moiety (θR-CtC-R 140-145°),3 in tandem with
the bulkiness of a Co2(CO)6 core, provides a unique opportu-
nity for influencing the configurations of the stereocenters gene-
rated alpha to the metal cluster. The chemistry of radical
counterparts, such as 2, has been a focus of systematic studies
in our laboratory,4 allowing for discovery of the spontaneous4b
and THF-mediated4c conversion of propargyl cations to the
Propargyl radical coupling represents a potentially viable
approach to generation of acyclic and cyclic alkadiynes with a
1,5-disposition of the triple bonds. The latter can readily be
converted, via conventional methods, to a variety of classes of
organic compounds (1,5-alkadienes, 1,4-/1,6-diketones, cyclo-
pentenes, cyclopentenones, cycloalkane-1,2-diols, enediynes,
fused carbocycles),1 further highlighting its value and signifi-
cance to synthetic organic chemistry. In a purely “organic”
setting, propargyl-propargyl coupling exhibits a poor regio-
selectivity due to acetylene-allene rearrangement, forming
nearly inseparable mixtures of functional group isomers.2a
Another drawback is that organic molecules do not provide
the anchoring points in proximity to the stereogenic centers so
that the stereochemistry of the head-to-head coupling products;
1,5-alkadiynes;could be controlled by auxiliary functional
groups, either sterically or electronically. Substantial quantities
of isomeric allenes (45-50%) are formed in intermolecular
coupling of propargyl alcohols with Ti(OiPr)2Cl2/Mg, along
with poor diastereo- and regioselectivities and low conversions
(∼70%).2b Despite the step economy, metal-catalyzed pro-
cesses (Ru, Pd) are limited in scope,2c,d with their yields and
diastereoselectivities declining in the presence of electron-do-
nating and electron-withdrawing substituents (Me; OMe and
(2) (a) Badanyan, Sh. O.; Voskanyan, M. G.; Chobanyan, Zh. A.
Russ. Chem. Rev. 1981, 50, 1074. (b) Yang, F.; Zhao, G.; Ding, Y.; Zhao, Z.;
Zheng, Y. Tetrahedron Lett. 2002, 43, 1289. (c) Onodera, G.; Nishibayashi,
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Tsutsumi, K.; Kurosawa, H. J. Org. Chem. 1995, 60, 4650.
(3) (a) Melikyan, G. G.; Nicholas, K. M. In Modern Acetylene
Chemistry; Stang, P. J., Diederich, F., Eds.; VCH Publishers: Weinheim,
1995; Chapter 4. (b) McGlinchey, M. J.; Girard, L.; Ruffolo, R. Coord.
Chem. Rev. 1995, 143, 331. (c) Amouri, H. E.; Gruselle, M. Chem. Rev.
1996, 96, 1077. (d) Went, M. Adv. Organomet. Chem. 1997, 41, 69.
(e) Green, J. R. Curr. Org. Chem. 2001, 5, 809. (f) Muller, T. J. J. Eur. J.
Org. Chem. 2001, 2021. (g) Teobald, B. J. Tetrahedron 2002, 58, 4133.
(4) (a) Melikyan, G. G.; Sepanian, S.; Riahi, B.; Villena, F.; Jerome,
J.; Ahrens, B.; McClain, R.; Matchett, J.; Scanlon, S.; Abrenica, E.;
Paulsen, K.; Hardcastle, K. I. J. Organomet. Chem. 2003, 683, 324.
(b) Melikyan, G. G.; Villena, F.; Sepanian, S.; Pulido, M.; Sarkissian, H.;
Florut, A. Org. Lett. 2003, 5, 3395. (c) Melikyan, G. G.; Villena, F.; Florut,
A.; Sepanian, S.; Sarkissian, H.; Rowe, A.; Toure, P.; Mehta, D.; Christian,
N.; Myer, S.; Miller, D.; Scanlon, S.; Porazik, M. Organometallics 2006, 25,
4680. (d) Melikyan, G. G.; Floruti, A.; Devletyan, L.; Toure, P.; Dean, N.;
Carlson, L. Organometallics 2007, 26, 3173. (e) Melikyan, G. G.; Wild,
C.; Toure, P. Organometallics 2008, 27, 1569. (f) Melikyan, G. G.;
Mikailian, B.; Sepanian, R.; Toure, P. J. Organomet. Chem. 2009, 694,
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Spencer, R.; Molnar, J. Tetrahedron Lett. 2010, 51, 2287. (j) Melikyan,
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*To whom correspondence should be addressed. E-mail: gagik.melikyan@
csun.edu.
(1) cis-/trans-Hydrogenation: (a) Larock, R. C. Comprehensive Organic
Transformations: a Guide to Functional Group Preparations, 2nd ed.; VCH:
New York, 1999; p 405. Hydration of alkynes: (b) Menashe, N.; Shvo, Y. J. Org.
Chem. 1993, 58, 7434. (c) Mizushima, E.; Sato, K.; Hayashi, T.; Tanaka, M.
Angew. Chem., Int. Ed. 2002, 41, 4563. Synthesis of pyrroles: (d) Ramanathan,
B.; Keith, A. J.; Armstrong, D.; Odom, A. L. Org. Lett. 2004, 6, 2957.
Intramolecular aldol condensation: (e) Hayashi, Y.; Sekizawa, H.; Yamaguchi,
J.; Gotoh, H. J. Org. Chem. 2007, 72, 6493, and references therein. Pinacol
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7599. Enediyne antibiotics: (g) Smith, A. L.; Nicolaou, K. C. J. Med. Chem.
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pubs.acs.org/Organometallics
Published on Web 07/15/2010
2010 American Chemical Society

Article
Organometallics, Vol. 29, No. 16, 2010 3557
upon the nature of a reducing agent (Zn4d,7 vs Cp2Co4d), the
reaction temperature (0-147 °C),4d,f and the type of radical
transformation involved (spontaneous,4b THF-mediated,4c
self-coupling,7 cross-couping4d). The lowest stereoselecti-
vities were observed in Zn-7 and Cp2Co4d-induced reduc-
tions (d,l-5:meso-5, 75:25 and 76:24, respectively), while
THF-mediated self-coupling reactions, albeit with a lower
mass efficacy, exhibited a higher level of d,l-diastereocontrol
(d,l-5:meso-5, 92:8).4d In order to study the impact of the
γ-substituent on the diastereoselectivity of propargyl coupl-
ing reactions, the reductions were carried out under standard-
ized conditions (50-fold excess of Zn, -50 °C, 5 min, then
20 °C, 1 h). The formation of dimer 5 occurred with a higher
stereoselectivity (d,l-5:meso-5, 89:11 vs 75:257 or 83:174d) and a
good overall yield (67.6%). Incorporation of methoxy groups
on the periphery of the aromatic nuclei, in a 3,4,5-pattern, did
not affect the stereoselectivity of the dimerization reac-
tion. Thus, the conversion of 3,4,5-(OMe)3 alcohol 8 to radical
dimer 9, via propargyl cation 10 and propargyl radical 11,
affordedadiastereomeric mixture in the ratio of d,l-9:meso-
9, 87:13 (Scheme 1). The chromatographic mobilities of d,l-
and meso-diastereomers are quite similar, making the isolation
of d,l-9 a costly and tedious task (56.6%).
Figure 1
respective radicals, stereoselective synthesis of d,l-hexestrol,4a
formation of topologically diverse d,l-1,5-alkadiynes,4a-c,f,g
efficient assembling of highly sought after 1,5-cyclodecadiynes,4e
generation of propargyl cations under neutral conditions,4g
expansion of the temperature range for the spontaneous pro-
pargyl cation-to-radical conversion (up to 147 °C),4f and reversal
of stereoselectivity in intramolecular reactions yielding otherwise
inaccessible meso-1,5-cyclodecadiynes (up to 97%).4h
The bent geometry3 of cobalt-complexed propargyl radicals
2 provides yet another avenue for controlling the stereochem-
istry of radical C-C bond formation, a 1,3-steric induction
over the metal-complexed triple bond. In particular, the pre-
sence of a bulky substituent at the γ-carbon atom in propargyl
radical 3 could play a dual role. First, due to the 1,3-repulsion,
the rotational freedom around a CR-Cβ propargyl bond can be
constrained. Second, unlike radicals 2with terminal triple bonds,
radicals 3, while converging, have to place bulky γ-substituents
and cobalt-alkyne units further apart from each other. Such a
spatial rearrangement could alter the stereochemical outcome of
the radical coupling reactions.
The concept of “remote stereocontrol” has long been used in
organic chemistry to impact the stereoselectivity in ionic and
radical reactions.5 In the cobalt-alkyne series, the 1,4-asym-
metric induction was successfully employed in condensation of
γ-alkoxy propargyl aldehydes with methyl anions and reduc-
tion of γ-alkoxy ketones.6 The diastereoselectivity of nucleo-
philic addition reactions was found to reverse, ranging from
anti:syn 96:4 to 6:94.6 In this account, we report on the first 1,3-
steric induction in radical reactions of the cobalt-alkyne com-
plexes. The current study was undertaken to determine if the
presence of a bulky γ-substituent could favorably affect the
stereochemistry of intermolecular propargyl-propargyl coupl-
ing reactions. Another objective was to test the efficacy of
stereodirecting auxiliary groups that could be subsequently
removed, providing an access to 1,5-alkadiynes, which are
otherwise inaccessible as individual diastereomers.
The impact of a γ-substituent upon diastereoselectivity of
coupling reactions was first tested by replacing an acetylenic
3
˚
hydrogen with a much bulkier, tert-butyl group (ΔV 96 A ,
PCModel). Propargyl alcohol 12 (R = H) was synthesized
by the condensation of lithiated tert-butylacetylene and benz-
aldehyde,4g,8a followed by the complexation with dicobaltocta-
carbonyl3,8b (Scheme 2). Its treatment with HBF43,4 yielded the
cation 13, which was reduced, at -50 °C, with a 50-fold excess
of Zn, affording, via requisite radicals 14, dimeric product 15.
The diastereoselectivity was enhanced by the tert-butyl group,
forming d,l- and meso-stereoisomers in the ratio of 95:5. In the
case of 3,4,5-(OMe)3 alcohol 16, the same synthetic protocol
formed the expected dimeric product via intermediate propar-
gyl cation 17 and its radical counterpart 18. Only a single,
d,l-diastereomer 19 could be isolated and structurally charac-
terized. These data represent a positive proof of concept that by
replacing an acetylenic hydrogen with a bulky, tert-butyl group,
the d,l-diastereoselectivity can be significantly enhanced, yielding
d,l-diastereomers 15 and 19 with an excellent stereoselectivity
(95:5 and 100:0, respectively).
d,l-Diastereomer 19 features an unusual NMR spectrum
in which 3-OMe and 5-OMe groups are “collapsed” instead
of being represented by sharp singlets.4e,f Molecular model-
ing confirmed that the d,l-configuration is extremely crowded,
with its conformational freedoms being severely restrained.
A high degree of steric hindrance might be the reason for its
limited stability, even at ambient temperature. To unambigu-
ously establish the relative configuration of d,l-19, its structure
was resolved by means of X-ray crystallography (Figure 2).9 As
an ORTEP diagram suggests, the bulky tert-butyl groups are
Results and Discussion
Cobalt-complexed propargyl alcohol 4 was involved in
dimerization reactions in different settings,4b-d,f,7 yielding
1,5-hexadiyne 5 as diastereomeric mixtures (Scheme 1). The
typical sequence included the conversion to the Co2(CO)6-
complexed propargyl cation 6, followed by its reduction to
radical 7 and the ensuing intermolecular coupling reaction.
The level of diastereocontrol was found to be dependent
(8) (a) Brandsma, L.; Verkruijsse, H. D. Synthesis of Acetylenes,
Allenes and Cumulenes; Elsevier: New York, 1981; p 80. (b) Greenfield, H.;
Sternberg, H. W.; Friedel, R. A.; Wotiz, J. H.; Markby, R.; Wender, I. J. Am.
Chem. Soc. 1956, 78, 120.
(9) (a) SMART Version 5.628; Bruker AXS, Inc., Analytical X-ray
Systems: Madison, WI, 2003. (b) SAINT Version 6.36A; Bruker AXS, Inc.,
Analytical X-ray Systems: Madison, WI, 2002. (c) Sheldrick, G. SADABS
(5) (a) Mitchell, H. J.; Nelson, A.; Warren, S. J. Chem. Soc., Perkin
Trans. 1 1999, 1899. (b) Mikami, K.; Shimizu, M.; Zhang, H.; Maryanoff,
B. E. Tetrahedron 2001, 57, 2917.
€
Version 2.10; University of Gottingen, 2003. (d) Sheldrick, G. M. A short
(6) Hayashi, Y.; Yamaguchi, H.; Toyoshima, M.; Nasu, S.; Ochiai,
K.; Shoji, M. Organometallics 2008, 27, 163.
(7) Melikyan, G. G.; Combs, R. C.; Lamirand, J.; Khan, M.;
Nicholas, K. M. Tetrahedron Lett. 1994, 35, 363.
history of SHELX.Acta Crystallogr. 2008, A64, 112. (e) Wilson, A. J. C., Ed.
International Tables for X-ray Crystallography, Vol. C; Kynoch, Academic
Publishers: Dordrecht, 1992; Tables 6.1.1.4 (pp 500-502) and 4.2.6.8
(pp 219-222).

3558 Organometallics, Vol. 29, No. 16, 2010
Melikyan et al.
Scheme 1. Propargyl Alcohols with Terminal Triple Bonds: Dimerization with a Low to Moderate Stereoselectivity
Scheme 2. Propargyl Alcohols with γ-tert-Butyl Substituents: Highly Stereoselective Dimerization
pushed away from each other in order to minimize the repul-
sion (θC9-C8-C7-C6 135.3°). Such an arrangement stands in
sharp contrast with that of 1,5-alkadiynes, having terminal
triple bonds:4a,7 cobalt-alkyne units are located gauche to
each other, along with an anti disposition of hydrogen atoms.
The aromatic rings are partially stacked on top of each other
with a dihedral angle θC24-C8-C7-C15 being equal to only
34.1°. Internal H atoms are arranged nearly orthogonally
(θH7-C7-C8-H8 = 93°), which represents a significant devia-
tion from an ideal gauche or anti disposition. A steric hindrance
also manifests itself in distorted dihedral angles around the
metal-complexed triple bonds (θC2-C1-C6-C7 = 11.6°;
the periphery of the aromatic rings impacts the relative
chromatographic mobility of d,l- and meso-diastereomers,
4g
with 3,4-(OMe)2 and 3,4,5-(OMe)3
4b,g
derivatives being
the most difficult to separate. For this reason, a γ-tert-butyl
group was replaced with a γ-trimethylsilyl moiety, which
could be easily removed under basic conditions, even at
ambient temperature.10 Silicon is a larger atom than carbon
11
(VdW radii: C 1.70 A; Si 2.10 A), and consequently, the
˚
˚
3
˚
volume of a Me3Si group is greater, by ∼17 A , than that of its
all-carbon counterpart, a t-Bu group.12 Given the enhanced
bulkiness of an auxiliary group, one could anticipate an even
higher d,l-diastereoselectivity in radical coupling reactions
due to the more efficient 1,3-steric induction.
θ
C8-C9-C10-C11 = 13.5°). The latter is reflective of the depar-
ture from the normally linear geometry found in cobalt-alkyne
γ-Trimethylsilyl propargyl alcohol 20 was synthesized in
two steps (45.3%) from commercial products, by utilizing
complexes.3
The observed 1,3-steric induction of a γ-tert-butyl group
upon the relative configuration of radical coupling products
can be exploited in a synthetically meaningful manner if the
stereodirecting moiety can act in an auxiliary capacity and be
removed after the radical carbon-carbon bond formation.
Stereoselective synthesis becomes of utmost importance in
those cases when the diastereomeric mixtures cannot be easily
resolved. In particular, introducing methoxy substituents on
(10) Alphonse, F.; Karim, R.; Cano-Soumillac, C.; Hebray, M.;
Collison, D; Garner, D.; Joule, J. Tetrahedron 2005, 614, 11010.
(11) (a) Bondi, A. J. Phys. Chem. 1964, 68, 441. (b) Mantina, M.;
Chamberlin, A. C.; Valero, R.; Cramer, C. J.; Truhlar, D. G. J. Phys. Chem. A
2009, 113, 5806.
3
˚
(12) PCModel, version 9.1: Me4C V = 138.14 A , Me4Si V = 156.74
3
3
3
3
˚
˚
˚
˚
A , ΔV = 18.60 A ; Me3CH V = 117.46 A , Me3SiH V = 133.60 A ,
3
˚
ΔV = 16.14 A .

Article
Organometallics, Vol. 29, No. 16, 2010 3559
Figure 2. ORTEP diagram of d,l-μ-η2-[5,6-di(30,40,50-trimethoxyphenyl)-2,2,9,9-tetramethyl-3,7-decadiyne]bis(dicobalthexacarbonyl) (19).
˚
Selected bond lengths (A) and angles (deg): C6-C7 1.52, C7-C8 1.57, C8-C9 1.52, C2-C1-C6-C7 11.6, C8-C9-C10-C11 13.5,
C9-C8-C7-C6 135.3, C24-C8-C7-C15 34.1, H7-C7-C8-H8 93.0.
Scheme 3. Propargyl Alcohols with a Removable γ-Me3Si Substituent: Highly Stereoselectivite Dimerization
the condensation-complexation sequence4g,8 (Scheme 3).
The treatment with HBF4 (6 equiv),3,4 followed by the
reduction with a 50-fold excess of Zn, afforded radical dimer
21 in high yield (81.0%) and with an excellent d,l-diastereo-
selectivity (d,l:meso, 99:1). Decomplexation with ceric ammo-
nium nitrate3a,g,4 allowed for release of an organic dimer, d,l-
22, which was then treated, without additional purification,
with NaOH in order to remove the auxiliary Me3Si groups.10
The parent radical dimer, d,l-23, was isolated as an individual
diastereomer in high yield (74.9% over two steps). Thus, a
five-step sequence allowed for utilizing the stereodirecting
ability of an auxiliary Me3Si group and assembling d,l-
diastereomer 23 in an isomerically pure form, in 27.5% overall
yield. The same strategy was applied for the stereoselective
synthesis of d,l-24 (Scheme 4), for which diastereomers are
notoriously difficult to isolate: milligram quantities of indivi-
dual isomers can be obtained by column chromatography,
in 12 h, by using ∼5 gallons of organic solvents! Requisite
alcohol 25 was synthesized in two steps (69.0%),4g,8 then con-
verted to the respective cationic species under acidic condi-
tions3,4 and reduced with Zn to yield d,l-26 with an excellent
d,l-diastereoselectivity (d,l:meso, 98.5:1.5) and in a good yield
(69.0%). The decomplexation3a,g,4-desilylation10 sequence
released pure d,l-24 in 69.5% yield over two steps. Thus, a
five-step sequence again allowed us to exploit a Me3Si group,
as an auxiliary moiety, and synthesize otherwise inaccessible,
isomerically pure d,l-diastereomer 24 in 33.1% overall yield.
The X-ray structure of d,l-24 represents an extended con-
formation with aryl groups positioned anti to each other
(θC20-C26-C18-C9 166.0°) (Figure 3). The dihedral angle between
two triple bonds is ideally gauche (θC25-C26-C18-C23 60.2°),
while the hydrogen atoms exhibit only a slight deviation from
an expected value (θH26-C26-C18-H18 68.4°). Conformationally,
the X-ray structure of d,l-24 represents a striking departure from
its metal-clustered counterpart d,l-19. The latter was forced to
place its bulky, γ-substituted cobalt-alkyne moieties anti to each

3560 Organometallics, Vol. 29, No. 16, 2010
Scheme 4. 1,3-Steric Induction in the Stereoselective Synthesis of d,l-1,5-Hexadiyne 24
Melikyan et al.
Scheme 5. Alternative Pre-d,l-dispositions of Converging Propargyl Radicals
Me3Si groups (Scheme 5). In the case of terminal propargyl
radicals (γ-H), hydrogen atoms, given their size, can be pointed
at each other in the pre-d,l-arrangement A. After the formation
of the CR-CR bond, according to X-ray crystal structures,4a,7
cobalt-alkyne units are arranged gauche to each other, with
acetylenic hydrogens being positioned in close proximity to
each other. When bulky t-Bu or Me3Si groups are introduced,
respective pre-d,l-arrangement B becomes destabilized due to
the repulsion between γ-substituents. To facilitate the conver-
gence, propargyl radicals can undergo a spatial rearrangement,
placing the bulky cobalt-alkyne units anti to each other (pre-
d,l-arrangement C). Dimerization would then form d,l-diastereo-
mer D, in which hydrogen atoms are positioned gauche to
each other, while bulky cobalt-alkyne units maintain an anti
disposition. Conformation D is consistent with the X-ray
structure of d,l-19 (Figure 2), featuring gauche-oriented aro-
matic rings and methine hydrogens along with the bulky
substituents;(t-BuCtC)Co2(CO)6;pointed away from each
other. Analogous crystal structures were reported by us for
topologically related radical dimers;γ-Et,4j γ-C6H4OMe4d;
further highlighting the generality of how propargyl radicals
respond conformationally to an increased bulkiness at the
remote γ-position.
Figure 3. ORTEP diagram of d,l-3,4-di(30,40,50-trimethoxyphenyl)-
˚
1,5-hexadiyne (24). Selected bond lengths (A) and angles (deg):
Conclusion
C9-C18 1.53, C18-23 1.46, C18-C26 1.56, C26-C20 1.52,
C26-C25 1.46; C9-C18-C26 112.7, C9-C18-C23 111.9,
C18-C26-C20 114.2, C20-C26-C25 110.9; C20-C26-C18-C9
166.0, C25-C26-C18-C23 60.2, H26-C26-C18-H18 68.4.
Due to 1,3-steric induction, the diastereoselectivity of intermo-
lecular coupling reactions of Co2(CO)6-complexed propargyl
radicals can be controlled by relatively large γ-substituents.
Steric repulsion forces radical species to converge in a manner
that places conflicting bulky substituents anti to each other.
Both permanent t-Bu and auxiliary Me3Si groups can sub-
stantially improve the diastereoselectivity of these reactions,
affording d,l-1,5-alkadiynes with excellent stereoselectivity
(γ-t-Bu 95-100%; γ-Me3Si 98.5-99%). Overall, the synthetic
strategy employing a Me3Si auxiliary group involves five steps
and yields, with 28-33% overall yields, pure d,l-diastereo-
mers, which are otherwise hardly accessible.
other, while holding aromatic rings in a partially eclipsed
manner. The steric relief attendant with the removal of γ-
substituents and metal cores allowed for aromatic rings to spring
out (d,l-19 θC24-C8-C7-C15 34.1° vs d,l-24 θC20-C26-C18-C9
166.0°), while placing the triple bonds gauche to each other
(d,l-19 θC9-C8-C7-C6 135.3° vs d,l-24 θC25-C26-C18-C23 60.2°).
The observed 1,3-steric induction can best be accounted
for in terms of the repulsion between γ-located, bulky t-Bu or

Article
Organometallics, Vol. 29, No. 16, 2010 3561
Experimental Section
stirred for 3 h at 0 °C, concentrated, and fractionated on silica
gel (100 g, PE:E, 10:1). The compound was reisolated on silica
gel (18 g, PE:E, 10:1) to yield 12 (300 mg, 21.1%) as a dark red
All manipulations of air-sensitive materials were carried out in
flame-dried Schlenk-type glassware on a dual-manifold Schlenk
line interfaced to a vacuum line. Argon and nitrogen (Airgas,
ultrahigh purity) were dried by passing through a Drierite tube
(Hammond). All solvents were distilled before use under dry
nitrogen over appropriate drying agents (ether, THF, from sodium
benzophenone ketyl; CH2Cl2, from CaH2; benzene, from sodium).
All reagents were purchased from Sigma-Aldrich and Acros and
used as received. Co2(CO)8 and Ce(NH4)2(NO3)6 were purchased
from Strem. NMR solvents were supplied by Cambridge Isotope
Laboratories. 1H and13C NMR spectra were recorded on a Bruker
DRX-400 (1H, 400 MHz) spectrometer. Chemical shifts were
referenced to internal solvent resonances and are reported relative
to tetramethylsilane. Spin-spin coupling constants (J) are given in
hertz. Melting temperatures (uncorrected) were measured on a
Mel-Temp II (Laboratory Devices) apparatus and an Optimelt
Automated Meltemp. Silica gel S735-1 (60-100 mesh; Fisher) was
used for flash column chromatography. Analytical and preparative
TLC analysis (PTLC) were conducted on silica gel 60 F254 (EM
Science; aluminum sheets) and silica gel 60 PF254 (EM Science;
w/gypsum; 20 ꢀ 20 cm), respectively. Eluents are ether (E) and
petroleum ether (PE). Mass spectra were run at the Regional
Center on Mass-Spectroscopy, UC Riverside, Riverside, CA
(Agilent 6210 LCTOF instrument with a Multimode source).
X-ray structures were determined at the crystallographic facility
at Emory University, Atlanta, GA.
1
oil. TLC (PE:E, 3:1): Rf 0.56. H NMR (400 MHz, CDCl3): δ
1.27 (9H, s, 3CH3), 2.30 (1H, d, OH, J = 3.2), 5.91 (1H, d, CH),
7.28-7.50 (5H, m, aromatic H). MS TOF: m/z calcd for
C19H15O6Co2 [M - OH]þ 456.9527, found 456.9535.
d,l-μ-η2-(2,2,9,9-Tetramethyl-5,6-diphenyl-3,7-decadiyne)bis-
(dicobalthexacarbonyl) (15). According to protocol A, alcohol 12
(94.8 mg, 0.2 mmol) was converted to the mixture of d,l-15 and
meso-15 in the ratio of 95:5 (NMR). Fractionation on preparatory
TLC (PE) afforded d,l-15 (56.9 mg, 62.2%) as dark brown crystals
and (t-BuCtCCH2Ph)Co2(CO)6 (5 mg, 5.5%) as a red oil. Isola-
tion of meso-15 was not carried out due to its instability. d,l-15 TLC
(PE:E, 10:1): Rf 0.65. Tdec: 110-135 °C (sealed capillary; dried by
1
coevaporation with benzene, 3 ꢀ 1 mL). H NMR (400 MHz,
CDCl3): δ 1.04 (18H, s, 6CH3), 4.89 (2H, s, 2CH), 7.14-7.33 (10H,
m, aromatic H). 13C NMR (100 MHz, C6D6): δ 32.4 (2(CH3)3C),
36.6 (C2, C9), 57.0 (C5, C6), 103.5, 114.2 (C3, C4, C7, C8), 127.2,
127.9, 132.8, 139.8 (aromatic C), 200.3 (CdO). MS TOF: m/z
calcd for C36H30O10Co4 [M - 2CO]- 857.9172, found 857.9150.
1
(t-BuCtCCH2Ph)Co2(CO)6 TLC (PE): Rf 0.43. H NMR (400
MHz, CDCl3): δ 1.34 (9H, s, 3CH3), 4.06 (2H, s, CH2), 7.24-7.41
(5H, m, aromatic H).
μ-η2-[1-(30,40,50-Trimethoxyphenyl)-2-pentyne-4,4-dimethyl-
1-ol]dicobalt Hexacarbonyl (16). According to protocol B, 3,3-
dimethyl-1-butyne (1.80 g, 22 mmol), n-BuLi (15 mL, 1.6 M, 24.0
mmol), 3,4,5-trimethoxybenzaldehyde (5.10 g, 26.0 mmol), and
dicobaltoctacarbonyl (8.27 g, 24.0 mmol) were converted, upon
washing the crude product with cold petroleum ether (0 °C, 6 ꢀ
50 mL), to complex 16 (2.62 g, 21.2%) as dark red crystals.
Zinc-Induced Dimerization of Co2(CO)6-Complexed Propar-
gyl Cations (Protocol A): d,l- and meso-μ-η2-(3,4-Diphenyl-1,5-
hexadiyne)bis(dicobalthexacarbonyl) (5). Under an atmosphere
of nitrogen, HBF4 Me2O (161 mg, 1.20 mmol) was added
T
decomp: 75-110 °C (sealed capillary; dried by coevaporation
3
1
dropwise (1 min) to a solution of 4 (83.6 mg, 0.2 mmol) in dry
ether (20 mL) at -20 °C and stirred for 45 min. The ethereal
layer was removed, and the cation was washed with dry ether
(2 ꢀ 15 mL) at -30 °C. The residual amount of ether was removed
under reduced pressure at -30 °C, and the cation was suspended in
dry CH2Cl2 (20 mL), cooledto-50 °C, andstirredfor15min. Zinc
(650 mg, 10 mmol) was added to the reaction mixture at -50 °C
and stirred for 5 min and then for an additional hour at 20 °C(TLC
control). The crude mixture was filtered though a short bed of
Florisil (1 cm), concentrated under reduced pressure (NMR: d,l-5:
meso-5, 89:11), and fractionated on preparatory TLC (PE, 2 runs)
to give d,l-5 (49.3 mg, 61.4%) and meso-5 (5.0 mg, 6.2%). Spectral
data were identical to those previously published by us.4c
with benzene, 3 ꢀ 1 mL). TLC (ether): Rf 0.68. H NMR (400
MHz, CDCl3): δ 1.30 (9H, s, t-Bu) 2.40 (1H, d, OH, J = 2.8), 3.80
(3H, s, OMe), 3.88 (6H, s, OMe), 5.85 (1H, d, CH), 6.70 (2H, s, 20-
H, 60-H). 13C NMR (100 MHz, CDCl3): δ 32.89, 36.81 (C4, C5),
56.39, 61.36, 74.54 (30/50-OMe; 40-OMe; C1), 102.49, 111.86
(CtC), 103.87, 138.48, 139.94, 153.58 (arom. C), 200.00 (CO).
MS FABþ: m/z 565 (Mþ þ H), 547 (Mþ - OH), 536 (Mþ -CO),
508 (Mþ -2CO), 480 (Mþ -3CO), 463 (Mþ -3CO -OH), 452
(Mþ - 4CO), 435 (Mþ - 4CO - OH),424(Mþ - 5CO), 396 (Mþ -
6CO), 348 (Mþ - 6CO - OMe - OH), 261 (Mþ - 6CO - 2Co -
OH). HR-MS/FABþ: calcd for Mþ - CO C21H22O9Co2
535.992778, found 535.994600.
d,l-μ-η2-[5,6-Di(30,40,50-trimethoxyphenyl)-2,2,9,9-tetramethyl-
3,7-decadiyne]bis(dicobalthexacarbonyl) (19). According to proto-
col A, alcohol 16 (423 mg, 0.75 mmol) was converted to d,l-19
(285 mg, 69.5%), a red-brown solid unstable at ambient tempera-
ture, which was isolated by using preparatory TLC (4 plates, 20 ꢀ
20 cm; PE:E, 2:1). TLC (PE:E, 1:3): Rf 0.59. 1H NMR (400 MHz,
CDCl3): δ 1.44 (18H, s, t-Bu), 3.53 (∼6H, br s, 30/50-OMe), 3.71
(∼6H, s, 40-OMe), 3.83 (∼6H, br s, 30/50-OMe), 4.79 (2H, s, 2CH),
6.17 (2H, br s, arom. H), 6.84 (2H, br s, arom. H). MS FABþ: m/z
1010 (Mþ - 3CO), 1009 (Mþ - 3CO - H), 982 (Mþ - 4CO),
926 (Mþ - 6CO), 898 (Mþ - 7CO), 870 (Mþ - 8CO), 871
(Mþ - 8CO - H), 843 (Mþ - 9CO - H), 814 (Mþ - 10CO),
786 (Mþ - 11CO), 758 (Mþ - 12CO), 727 (Mþ - 12CO - OMe),
699 (Mþ - 12CO - Co), 668 (Mþ - 12CO - OMe - Co), 640
(Mþ - 12CO - 2Co). HR-MS/DEI: calcd for C41H42O15Co4
(Mþ - 3CO) 1009.985162, found 1009.990300. Single crystals
suitable for X-ray structure analysis (Figure 2) were obtained at
ambient temperature by a slow evaporation of dichloromethane
solution (NMR tube) under N2 atmosphere.
d,l- and meso-μ-η2-[3,4-Di(30,40,50-trimethoxyphenyl)-1,5-hexa-
diyne]bis(dicobalthexacarbonyl) (9). According to protocol A,
alcohol 8 (101.6 mg, 0.2 mmol) was converted to the mixture of
d,l-9 and meso-9 in the ratio of 87:13 (NMR). Fractionation on
a silica gel column (50 g, degassed, PE:E, 1:2) afforded d,l-9
(55.6 mg, 56.6%) as dark red-brown crystals and meso-9 (5 mg,
5.1%; contains minute quantities of inseparable impurities) as
brown crystals. Spectral data were identical to those previously
published by us.4b
Condensation of Lithium Acetylides with Aromatic Aldehydes
(Protocol B): μ-η2-(4,4-Dimethyl-1-phenylpent-2-yn-1-ol)dico-
balt Hexacarbonyl (12). Under an atmosphere of nitrogen, 3,3-
dimethyl-1-butyne (246 mg, 3 mmol) in THF (10 mL) was added
dropwise (10 min) to a solution of n-BuLi (2.8 mL, 1.6 M) in
THF (30 mL) at -10 °C. The reaction mixture was stirred for 5 h
at -10 °C; then a solution of PhCHO (318 mg, 3 mmol) in THF
(10 mL) was added dropwise (10 min) at -10 °C. After stirring
for 20 h at 20 °C, the reaction mixture was cooled to 0 °C and
quenched with saturated NH4Claq (20 mL). An aqueous layer
was extracted with ether (3 ꢀ 50 mL), and combined ethereal
fractions were dried (Na2SO4). Upon concentration under
reduced pressure (half of the initial volume), under an atmo-
sphere of nitrogen, the crude alcohol (564 mg, 3 mmol; assuming
100% yield) was added to a solution of dicobaltoctacarbonyl
(1.13 g, 3.3 mmol) in dry ether (20 mL) at 0 °C. The mixture was
X-ray Crystallography of d,l-19 and d,l-24.9 Suitable crystals
of d,l-19 and d,l-24 were coated with Paratone N oil, suspended
in a small fiber loop, and placed in a cooled nitrogen gas stream
at 173 K on a Bruker D8 SMART APEX CCD sealed-tube dif-
˚
fractometer with graphite-monochromated Mo KR (0.71073 A)
radiation. Data were measured using a series of combinations of
phi and omega scans with 10 s frame exposures and 0.3° frame

3562 Organometallics, Vol. 29, No. 16, 2010
Melikyan et al.
widths. Data collection, indexing, and initial cell refinements were
all carried out using SMART9a software. Frame integration and
final cell refinements were done using SAINT9b software. The
SADABS9c program was used to carry out absorption corrections.
The structures were solved using direct methods and differ-
ence Fourier techniques (SHELXTL, V6.12).9d Hydrogen atoms
were placed in their expected chemical positions using the HFIX
command and were included in the final cycles of least-squares
with isotropic Uij’s related to the atom’s ridden upon. All non-
hydrogen atoms were refined anisotropically. Scattering factors
and anomalous dispersion corrections are taken from the Inter-
national Tables for X-ray Crystallography.9e Structure solution,
refinement, graphics, and generation of publication materials
were performed by using SHELXTL, V6.12 software.
the reaction mixture was stirred for 16 h. The suspension was
diluted with ether (3 mL), and the organic layer was washed with
saturated NaClaq (3 ꢀ 5 mL), dried (MgSO4), and concentrated
under reduced pressure. Fractionation on a preparative TLC
plate (1/2; PE, 2 runs) afforded dl-23 (13.1 mg, 74.9% over two
steps), which was fully characterized in the previous account.4g
μ-η2-[3-Trimethylsilyl-1-(30,40,50-trimethoxyphenyl)prop-2-yn-1-ol]-
dicobalt Hexacarbonyl (25). According to protocol B, trimethyl-
silyl acetylene (588 mg, 6 mmol), n-BuLi (4.5 mL, 1.6 M), 3,4,5-
(MeO)3C6H2CHO (1.18 g, 6 mmol), and dicobaltoctacarbonyl
(2.26 g, 6.6 mmol) afforded, upon fractionation on a silica gel
column (300 g, PE:E, 2:1), alcohol 25 (2.40 g, 69.0%) as a brick
red powder. Mp: 98-107 °C (sealed capillary; dried by coeva-
poration with benzene, 3 ꢀ 1 mL). TLC (PE:E, 1:1): Rf 0.44. 1H
NMR (400 MHz, CDCl3): δ 0.25 (9H, s, 3CH3), 2.39 (1H, d, OH,
J = 2.8), 3.80 (3H, s, OCH3), 3.88 (6H, s, 2OCH3), 5.84 (1H, d,
CH), 6.69 (2H, s, aromatic H). 13C NMR (400 MHz, CDCl3):
δ 0.66 (Me3Si), 56.04 (OMe), 60.91 (OMe), 74.75 (C3), 78.13 (C1/
C2), 103.02 (aromatic C), 116.20 (C2/C1), 138.17, 139.73, 153.31
(aromatic C), 199.83 (CO). MS TOF: m/z calcd for C21H26NO10-
SiCo2 [MNH4]þ 597.9984, found 597.9978. Anal. Found: C,
43.48; H, 3.64. C21H22O10SiCo2 requires: C, 43.46; H, 3.82.
d,l-μ-η2-[1,6-Di(trimethylsilyl)-3,4-di(30,40,50-trimethoxyphenyl)-
1,5-hexadiyne]bis(dicobalthexacarbonyl) (26). According to pro-
tocol A, alcohol 25 (116 mg, 0.2 mmol) was converted to the
mixture of d,l-26 and meso-26 in the ratio of 98.5:1.5 (NMR).
Fractionation on a preparatory TLC plate (PE:E, 1:1) afforded d,
l-26 (78.0 mg, 69.0%) as dark brown crystals. TLC (PE:E, 1:1): Rf
0.44. Mp: 97-126 °C (w/dec; sealed capillary; dried by coeva-
poration with benzene, 3 ꢀ 1 mL). 1H NMR (400 MHz, CDCl3):
δ 0.14 (18H, s, 6CH3), 3.60-3.90 (12H, br s, 4OCH3), 3.78 (6H, s,
μ-η2-(3-Trimethylsilyl-1-phenylprop-2-yn-1-ol)dicobalt Hexa-
carbonyl (20). According to protocol B, trimethylsilyl acetylene
(294 mg, 3 mmol), n-BuLi (2.8 mL, 1.6 M), PhCHO (318 mg,
3 mmol), and dicobaltoctacarbonyl (1.13 g, 3.3 mmol) were
converted, upon fractionation on a silica gel column (200 g,
PE:E, 10:1), to alcohol 20 (666 mg, 45.3%) as a dark red powder.
Mp: 51-52 °C (sealed capillary; dried by coevaporation with
1
benzene, 3 ꢀ 1 mL). TLC (PE:E, 3:1): Rf 0.63. H NMR (400
MHz, CDCl3): δ 0.23 (9H, s, 3CH3), 2.34 (1H, d, OH, J = 3.2),
5.92 (1H, d, CH), 7.27-7.48 (5H, m, aromatic H). 13C NMR
(400 MHz, CDCl3): δ 0.59 (Me3Si), 74.82 (C3), 78.22, 116.37
(C1, C2), 125.84, 128.32, 128.53, 143.90 (aromatic C), 199.71
(CO). MS TOF: m/z calcd for C18H15O6SiCo2 [M - OH]þ
472.9296, found 472.9307. MS TOF FDþ: m/z Mþ 490. Anal.
Found: C, 43.71; H, 3.31. C18H16O7SiCo2 requires: C, 44.10;
H, 3.29.
d,l-μ-η2-[1,6-Di(trimethylsilyl)-3,4-diphenyl-1,5-hexadiyne]bis-
(dicobalthexacarbonyl) (21). According to protocol A, alcohol 20
(98.0 mg, 0.2 mmol) was converted to d,l-21 (76.6 mg, 81.0%; d,l-
21:meso-21, 99:1) as dark brown crystals. TLC (PE:E, 10:1): Rf
0.62. Tdec: 87-92 °C (sealed capillary; dried by coevaporation
with benzene, 3 ꢀ 1 mL). 1H NMR (400 MHz, CDCl3): δ 0.16
(18H, s, 6CH3), 4.88 (2H, s, 2CH), 6.97 (4H, br d, aromatic H,
J = 6.0), 7.17-7.31 (6H, m, aromatic H). 13C NMR (100 MHz,
CDCl3): δ 1.84 (Me3Si), 61.41 (C3, C4), 77.73, 114.12 (C1, C2,
C5, C6), 127.70, 127.94, 131.46, 140.44 (aromatic C), 199.72,
200.58 (CO). MS TOF: m/z calcd for C34H30O10Si2Co4 [M -
2CO]- 889.8711, found 889.8685. MS TOF FDþ: m/z Mþ 946.
Anal. Found: C, 45.52; H, 3.45. C36H30O12Si2Co4 requires: C,
45.68; H, 3.19.
2OCH3), 4.80 (2H, s, 2CH), 6.00-6.90 (4H, br, aromatic H). 13
C
NMR (100 MHz, CDCl3): δ 1.82 (Me3Si), 56.45 (OMe), 60.86
(C3, C4, OMe), 78.35 (C1/C6 or C2/C5), 110.55 (aromatic C),
115.16 (C1/C6 or C2/C5), 136.28, 138.83, 152.45 (aromatic C),
199.79, 200.71 (CO). MS TOF: m/z calcd for C42H46NO18Si2Co4
[MNH4]þ 1143.9576, found 1143.9608. Anal. Found: C, 45.35;
H, 3.89. C42H42O18Si2Co4 requires: C, 44.77; H, 3.76.
d,l-3,4-Di(30,40,50-trimethoxyphenyl)-1,5-hexadiyne (24). Accord-
ing to protocol C, dl-26 (22.5 mg, 0.02 mmol) was treated with
Ce(NH4)2(NO3)6 (132 mg, 0.24 mmol; 6 portions), BnMe3NCl
(0.9 mg, 0.005 mmol), and NaOH (8.0 mg, 0.2 mmol) to afford,
upon fractionation on a preparatory TLC plate (1/4; PE:E, 1:2),
d,l-24 (5.7 mg, 69.5% over two steps), which was fully characterized
in the previous account.4g Single crystals suitable for X-ray structure
analysis (Figure 3) were obtained by ethanol vapor diffusion into a
solution of d,l-24 in ethyl acetate at ambient temperature (4 days).
Decomplexation-Desilylation Sequence (Protocol C): d,l-3,4-
Diphenyl-1,5-hexadiyne (23). Under an atmosphere of nitrogen,
at -78 °C, a solution of degassed Ce(NH4)2(NO3)6 (333 mg,
0.608 mmol) in acetone (8 mL, degassed) was added (10 min) to a
solution of dl-21 (71.9 mg, 0.076 mmol) in acetone (10 mL,
degassed). The reaction mixture was stirred at -78 °C for 15 min,
then at -50 °C for 30 min. An additional amount of Ce(NH4)2-
(NO3)6 (125 mg, 0.228 mmol; 3 portions) was added to bring the
reaction to completion (TLC control). The mixture was treated
(-78 °C, N2) with a degassed saturated solution of NaClaq
(20 mL), transferred to a separatory funnel, and extracted with
ether (2 ꢀ 15 mL). The combined organic layers were dried
Acknowledgment. This material is based upon work
supported by the National Science Foundation under
CHE-0707865. The authors are also greatly indebted to
the Office of Graduate Studies, Research and Inter-
national Programs, and University Corporation, California
State University Northridge, for their generous support.
˚
(molecular sieves 4 A), and ether was removed under reduced
Supporting Information Available: CIF files and tables giving
crystallographic details, bond distances and angles, atomic
coordinates and equivalent isotropic displacement parameters,
and torsion angles for d,l-19 and d,l-24. This material is available
free of charge via the Internet at http://pubs.acs.org.
pressure. At 0 °C, the crude product 22 and BnMe3NCl (3.5 mg,
0.019 mmol) were combined and dissolved in acetonitrile (3 mL).
A solution of NaOH (30.4 mg, 0.76 mmol) in H2O (2 mL) was
added dropwise (2 min), the temperature was raised to 20 °C, and