Quick, efficient conversion of phenones to conjugated trienes via germylene cycloaddition

Article abstract of DOI:10.1021/om0108696

The conversion of phenones into conjugated trienes via germylene based cycloaddition reaction was investigated. The molecular modeling calculations based on DFT theory were performed to explore the comparative energetics of the formed products. The cycloaddition reaction at room temperature gave quantitative results that had some functional group tolerance.

Full text of DOI:10.1021/om0108696

Organometallics 2002, 21, 457-459
457
Qu ick , Efficien t Con ver sion of P h en on es to Con ju ga ted
Tr ien es via Ger m ylen e Cycloa d d ition
Ryan D. Sweeder, Fern A. Edwards,† Karla A. Miller,
Mark M. Banaszak Holl,* and J eff W. Kampf
The University of Michigan, Ann Arbor, Michigan 48109-1055
Received October 3, 2001
Summary: The germylene Ge[CH(Si(CH3)3)2]2 reacts with
phenones to give conjugated trienes. This reaction is
quantitative at room temperature in minutes and has
some functional group tolerance.
The phenone group, C6H5CO, is a common entity in
both commercial and natural products. The typically
observed chemistry of this fragment includes electro-
philic aromatic substitution on the ring and nucleophilic
F igu r e 1. Insertion products before (A) and after (B) a
attack at the ketone. However, the array of standard
organic methodologies designed to modify the double
bonds present in the ring fail to work because of the
added stabilization due to aromaticity. A reagent that
could break the aromaticity, rapidly generate ene and
diene moieties under mild conditions, show functional
group tolerance, and do so in good yield could be of great
value. We now report that these goals can be ac-
complished using the germylene Ge[CH(SiMe3)2]2 (1).1,2
Several intriguing precedents in the literature suggest
the mild conversion of a phenone to a conjugated triene
might be possible. A conjugated triene species (A in
Figure 1) is proposed as an intermediate in the reaction
between silylenes and phenones.3-6 However, a 1,3-
hydrogen shift of a ring hydrogen to the carbonyl carbon
typically reestablishes the aromaticity in the final
product (B in Figure 1). A notable exception is a recent
example where J utzi et al. isolated a triene product from
the reaction of decamethylsilicocene with benzophenone
or acetophenone carried out at 50 °C for 3-5 days.5
Unfortunately, X-ray crystallographic characterization
of this unusual fragment was not obtained. We report
the synthesis and characterization of a similar class of
compounds generated using the stable germylene 1. In
stark contrast to the silylenes, all of the germanium
products are stable to the 1,3-hydrogen shift that would
reestablish aromaticity.
1,3-hydrogen shift.
in 3 min. Removal of solvent in vacuo results in a
quantitative yield (via NMR) of a yellow solid (3).7 The
1H NMR spectrum contains peaks at 6.790, 6.025, and
5.687 ppm consistent with a conjugated triene and a
peak at 3.970 ppm for the ipso CH bonded to the
germanium. The IR spectrum exhibits no ν(CdO) or
ν(Ge-H). The parent ion observed by FAB-MS (573.3
amu) is also consistent with the proposed structure.
Finally, conjugation of the triene to the second phenyl
ring results in a yellow color and a visible absorbance
with λmax at 412 nm. 1 reacts with isobutyrophenone to
give 4, where no equivalent λmax is observed, due to the
shorter conjugation without the phenyl ring. In all, these
spectroscopic data suggest the formation of a triene
species as illustrated by A in Figure 1. The elemental
analysis is consistent with this hypothesis.
Propiophenone reacts with 1 in a similar manner to
form a white solid (5). A suitable single crystal for X-ray
crystallographic analysis was grown by slow evaporation
from benzene solution, and the assignment of the triene
structure was confirmed (Figure 2). An equal mixture
of two different enantiomers was present in the Pca21
space group. Alternating double and single bonds for
the conjugated triene were observed. The new conju-
gated double bonds are forced out of planarity, with
dihedral angles of 15 and 20°. The angle C6-C7-C2
has become 112.2(4)°, indicative of the sp3 hybridization
The chemistry of 1 with phenones leads to the
quantitative formation of the conjugated triene species
at ambient temperature within 30 min. For example,
compound 1 reacts with benzophenone (2) in tetra-
hydrofuran (THF) to produce a bright yellow solution
(7) Benzophenone (141 mg, 0.774 mmol) was added to 1 (300 mg,
0.766 mmol) in 8 mL of THF. A bright yellow solution was immediately
formed. The solution was stirred for 15 min, and the volatiles were
removed in vacuo. The residue contained the product along with the
excess benzophenone. Cold recrystallization in a dry ice/2-propanol
bath from acetonitrile afforded 183 mg of analytically pure product
† Current address: Cameron University, Lawton, OK 73505-6377.
(1) Neumann, W. P. Chem. Rev. 1991, 91, 311-334.
(2) Fjeldberg, T.; Haaland, A.; Schilling, B. E. R.; Lappert, M. F.;
Thorne, A. J . J . Chem. Soc., Dalton Trans. 1986, 1551-1556.
(3) Ando, W.; Ikeno, M.; Senkiguchi, A. J . Am. Chem. Soc. 1977,
99, 6447-6449.
(4) Belzner, J .; Ihmels, H.; Pauletto, L.; Noltemeyer, M. J . Org.
Chem. 1996, 61, 3315-3319.
(5) J utzi, P.; Eikenberg, D.; Bunte, E.-A.; Mo¨hrke, A.; Neumann,
B.; Stammler, H.-G. Organometallics 1996, 15, 1930-1934.
(6) Gehrhus, B.; Hitchcock, P. B.; Lappert, M. F. Organometallics
1997, 16, 6, 4861-4864.
(41.6% yield). 1H NMR (C6D6): δ 7.75 (d, J HH ) 8.0 Hz, 2 H, o-Ar H),
3
3
3
7.18 (t, J HH ) 7.6 Hz, 2 H, m-Ar H), 7.06 (t, J HH ) 7.2 Hz, 1 H, p-Ar
3
H), 6.79 (dm, J HH ) 10.0 Hz, 1 H, CH), 6.03 (m, 2 H, CH), 5.69 (m, 1
H, CH), 3.97 (s, 1 H, CH-Ge), 0.31 (s, 9 H, TMS), 0.24 (s, 9 H, TMS),
0.23 (s, 9 H, TMS), and 0.16 (s, 11 H, TMS, 2SiCHGe). 13C NMR
(C6D6): δ 154.49 (C-O); 136.81, 128.45, and 128.31 (Ar); 126.40,
126.05, 124.96, 120.08, and 111.63 (CdC); 38.73 (CH-Ge); 13.72 and
11.92 (SiCHGe); 3.74, 3.49, 3.40, and 3.05 (TMS). IR: no Ge-H or Cd
O. GC/MS: showed Ge(CH(TMS2)2 and benzophenone only. UV/vis:
λ
max412 and 239 nm. Anal. Calcd for C27H48GeOSi4: C, 54.56; H, 8.43.
Found: C, 54.53; H, 8.48. FAB/MS: M+ at m/z 573.3.
10.1021/om0108696 CCC: $22.00 © 2002 American Chemical Society
Publication on Web 01/03/2002

458 Organometallics, Vol. 21, No. 3, 2002
Communications
bonds,1,12,13 it makes the functional group tolerance of
1 with 4,4′-dichlorobenzophenone and benzophenone
imine more noteworthy. In each case, rather than
undergo insertion, the germylene instead exclusively
activates the aromatic ring, forming compounds 6 and
9.
The phenone activation is reversible. During at-
tempted purification via sublimation of 3 at 90 °C, both
germylene and 2 were separately observed in NMR
spectra of the sublimate and residue. Separately, injec-
tion of any of the germylene-phenone reaction products
into a GC/MS instrument results only in the elution of
the phenone 1. Exchange reactions also support the
reversibility of the reaction. The placement of 3 in a
solution with propiophenone yields 5 and free 2. Start-
ing with compound 5 and 2 led to the same product
ratio, demonstrating the presence of an equilibrium.
Addition of benzil to a benzene solution of 3 yields
trapped germylene and free 2.14
Molecular modeling calculations have been performed
to explore the comparative energetics of the products
formed. A noteworthy comparison is the energy of the
activated triene with the aromatic product resulting
from the 1,3-hydrogen shift. DFT calculations performed
at the pBP/DN*15 and Becke 3:LYP/LACVP**16 level of
theory indicate that isomer B (Figure 1) is more stable
than isomer A by 21-25 kcal/mol for compound 3,
suggesting that 3 is a kinetic product that could undergo
the 1,3-shift upon heating. However, only reversion to
reactants is observed experimentally in the absence of
solvent. This implies the kinetic barrier to reversion
must be significantly lower than that for the 1,3-shift.
F igu r e 2. ORTEP diagram of 5. Selected bond angles (deg)
and distances (Å): Ge1-O1, 1.857(3); Ge1-C7, 1.981(5);
C1-C2, 1.366(7); C2-C3, 1.448(8); C3-C4, 1.349(7); C4-
C5, 1.455(8); C5-C6, 1.338(7); C6-C7, 1.498(7); Ge1-O-
C1, 109.9(3); C1-C2-C7, 117.3(4); C7-Ge1-O1, 90.51(18).
Sch em e 1. Rea ction s of 1 w ith a Va r iety of
P h en on es
DFT calculations also suggest the formation of the
conjugated triene is enthalpically more stable than the
phenone and germylene independently.15 By comparison
of the product energy versus the reactants, it can be
determined that the reactions of 1 with 2, 4,4′-dimethyl-
benzophenone, 9-fluorenone, and isobutyrophenone lead
to products that are 10.2, 8.7, 3.9, and 2.4 kcal/mol,
respectively, more thermally stable that the individual
reactants. Since the 9-fluorenone reaction is thermo-
dynamically favorable, there must be some other reason
that the reaction does not occur, possibly an unfavorable
transition state. Calculations for methyl benzoate sug-
gest an increase of 19.2 kcal/mol, likely the reason no
reaction is observed. Similar calculations predict that,
for 4-methylbenzophenone, 8a is 0.7 kcal/mol more
favorable than 8b. This suggests a 3.3:1 ratio of 8a to
8b, somewhat larger than the experimentally observed
ratio of 1.4:1.
at C7. The small O-Ge-C7 angle of 90.51(18)° may be
due to the steric bulk of the ligands.
A number of other phenone species yield products
similar to 2 and propiophenone (Scheme 1). Interest-
ingly, the electronic effects induced by substitution on
the ring cause only subtle differences in the formation
of the product for many examples. The reaction occurs
with both weakly electron withdrawing and releasing
groups present on the rings (4,4′-dichlorobenzophenone
and 4,4′-dimethylbenzophenone respectively forming
compounds 6 and 7). Also, a mixture of products, 8a and
8b in a 1.4:1 ratio, is observed in the reaction of 1 with
4-methylbenzophenone, suggesting the unsubstituted
ring is the thermodynamically favored product (vide
infra). Curiously, 9-fluoreneone and methyl benzoate do
not react with the germylene, although the phenone
moiety is still present. Finally, since germylenes can
insert or undergo other reactions with C-X1,8-12 or N-H
Initially, there are a few viable mechanisms for the
addition of the germylene to a phenone moiety. In
addition to a concerted 1,4-addition mechanism, dipolar,
single electron transfer (SET) or diradical mechanisms
are possible. If one considers a single resonance form
(12) Riviere, P., Riviere-Baudet, M., Satge, J ., Davies, A. G., Eds.
Comprehensive Organometallic Chemistry II; Pergamon Press: London,
1995; Vol. 2, pp 137-217.
(13) Klein, B.; Neumann, W. P.; Weisbeck, M. P.; Wienken, S. J .
Organomet. Chem. 1993, 446, 149-159.
(14) Litz, K. E.; Bender, J . E.; Sweeder, R. D.; Banaszak-Holl, M.
M.; Kampf, J . W. Organometallics 2000, 19, 1186-1189.
(15) Spartan 5.0; Wavefuction, Inc., 18401 Von Karman Ave., Suite
370, Irvine, CA 92612, 1998.
(16) J aguar 3.5 Release 31; Schrodinger, Inc., 121 SW Morrison,
Suite 1212, Portland, OR 97204, 1998.
(8) Ohgaki, H.; Ando, W. J . Organomet. Chem. 1996, 521, 387-
389.
(9) Brauer, G.; Maslov, A.; Neumann, W. J . Organomet. Chem.
1989, 373, 11-19.
(10) Ko¨cher, J .; Lehnig, M.; Neumann, W. Organometallics 1988,
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(11) Schriewer, M.; Neumann, W. J . Am. Chem. Soc. 1983, 105,
897-901.

Communications
Organometallics, Vol. 21, No. 3, 2002 459
Sch em e 2. Rea ction of 1 w ith Cyclop r op yl P h en yl
Keton e
ring are not observed, the dipolar, SET, and diradical
mechanisms appear improbable. Further support for a
concerted reaction comes from exploring the reaction of
1 with 2 in THF, diethyl ether, benzene, and hexanes.
This leads to the observation that the reaction proceeds
at the same rate in each solvent, a characteristic
consistent with concerted or radical mechanisms but
inconsistent with dipolar or SET mechanisms.
In summary, the reaction of stable germylene 1 with
the phenone functional group provides a facile method
for converting a phenone into a conjugated triene
fragment in high yield and purity. The reaction has been
shown to be tolerant of the presence of some functional
groups.
of the phenone, one of the double bonds is located â to
the carbonyl poised for the 1,4-addition typical of
dimethylgermylene with vinyl ketones.17 The dipolar,
SET, and diradical mechanisms seem unlikely upon
consideration of the reaction of 1 with cyclopropyl
phenyl ketone (Scheme 2) to form 10. The development
of either a positive charge or a radical on the carbonyl
carbon should lead to ring opening of the cyclopropyl
ring.18,19 Since products derived from the opening of the
Ack n ow led gm en t. Support for this work from the
Research Corp. is gratefully acknowledged. M.M.B.H.
thanks the Alfred P. Sloan Foundation for a research
fellowship (1999-2002).
Su p p or tin g In for m a tion Ava ila ble: Text giving full
experimental and spectroscopic details for all compounds
reported. This material is available free of charge via the
Internet at http://pubs.acs.org.
(17) Michels, F.; Neumann, W. P. Tetrahedron Lett. 1986, 27, 2455.
(18) Dieter, R. K.; Pounds, S. J . Org. Chem. 1982, 47, 3174-3177.
(19) Tanko, J . M.; Phillips, J . P. J . Am. Chem. Soc. 1999, 121, 6078-
6079.
OM0108696