A novel route to 2-cyclohexenones via reaction of the manganese carbene anions [(η5-MeC5H4)(CO) 2Mn=C(OEt)CHR]- (R = H, Me) with α,β-unsaturated ketones

Article abstract of DOI:10.1021/om9704206

The carbene anions [Cp×(CO)₂Mn=C(OEt)-CHR]- ([1]^-, Cp'× = η⁵-MeC₅H₄; R = H, Me) react at -78 °C with the α,β-unsaturated ketones R¹H)C=C(H)C{O}-Me (2, R¹ = H, Me, Ph) to give the Michael adducts Cp×(CO)₂Mn=C(OEt)CH(R)CH(R¹)CH₂C{O}Me (3) upon acidic hydrolysis at low temperature. By contrast, quenching the reaction after warming up to room temperature allows isolation of the cyclohexenone complexes Cp×(CO)₂Mn(η²-CH=CHCH(R)CH(R¹)CH ₂C{O} (5), from which the corresponding substituted 2-cyclohexenones (9) can be readily released by reaction with triphenylphosphine or carbon monoxide.

Full text of DOI:10.1021/om9704206

Organometallics 1997, 16, 3873-3875
3873
A Novel Rou te to 2-Cycloh exen on es via Rea ction of th e
Ma n ga n ese Ca r ben e An ion s
[(η5-MeC5H4)(CO)2Mn dC(OEt)CHR]- (R ) H, Me) w ith
r,â-Un sa tu r a ted Keton es
Carole Mongin, Noe¨l Lugan,*,† and Rene´ Mathieu
Laboratoire de Chimie de Coordination du CNRS (UPR 8241), 205 route de Narbonne,
31077 Toulouse Cedex 4, France
Received May 20, 1997X
Summary: The carbene anions [Cp′(CO)2MndC(OEt)-
CHR]- ([1]-, Cp′ ) η5-MeC5H4; R ) H, Me) react at -78
°C with the R,â-unsaturated ketones R1(H)CdC(H)C{O}-
Me (2, R1 ) H, Me, Ph) to give the Michael adducts
Cp′(CO)2MndC(OEt)CH(R)CH(R1)CH2C{O}Me (3) upon
acidic hydrolysis at low temperature. By contrast,
quenching the reaction after warming up to room tem-
perature allows isolation of the cyclohexenone complexes
-78 °C,5a effectively readily react with the R,â-unsatur-
ated ketones R1(H)CdC(H)C{O}R2 (2, see Table 1).
After acidic hydrolysis at low temperature, the Michael-
addition complexes Cp′(CO)2MndC(OEt)CH(R)CH(R1)-
CH2C(O)R2 (3, Scheme 1; Table 1, conditions A, entries
1-8) are obtained in moderate to excellent yields.6 Only
from the reaction between [1a ]- and 2d (Table 1, entry
4) is the aldol adduct Cp′(CO)2MndC(OEt)CH2C(Me)-
(OH)CHdCH(Ph) (4d ) detected in trace amounts. In
contrast to the previously reported Michael additions
Cp′(CO)2Mn(η2-CH)CHCH(R)CH(R1)CH2C{O}) (5), from
which the corresponding substituted 2-cyclohexenones (9)
can be readily released by reaction with triphenylphos-
phine or carbon monoxide.
of [(CO)5CrdCOCH2CH2CH]- to 2c or 2d that were not
found to be diastereoselective,3a we find that 3e, 3g, and
3h are, respectively, formed with diastereomeric ex-
cesses of 33%, 50%, and 70% (Table 1, entries 5, 7-8).
Combinations of NMR and X-ray diffraction studies
allowed us to establish an anti configuration for each
of the major diastereomers.7,8
Carbene anions formed upon deprotonation of Fis-
cher-type carbenes at the â-carbon atom are known to
react with a variety of electrophilic substrates,1 includ-
ing carbonyl compounds, to give aldol2 or Michael3
adducts. Until recently,4 such reactions were almost
exclusively developed with group 6 carbene anions. Our
own interest in manganese derivatives [Cp′(CO)2Mnd
C(OR′)CHR]- ([1]-) stems in part on experimental
evidences of their enhanced reactivity toward electro-
philes as compared with the chromium and tungsten
analogs [(CO)5M)C(OR’)CHR]-.5 This can be rational-
ized in terms of the relative acceptor abilities of the
fragments Cp′(CO)2Mn (Cp′ ) η5-MeC5H4) and (CO)5M
(M ) Cr, W). Keeping in mind the pioneering work of
Casey et al. on the chromium alkylalkoxy carbene
anion,3a we were curious to examine the reactivity of
[1]- (R′ ) OEt; R ) H, Me) toward R,â-unsaturated
ketones. This led us to observe the formation of
cyclohexenone complexes, thus revealing an unprec-
edented reactivity pattern for these carbene anions.
The carbene anions [Cp′(CO)MndC(OEt)CHR]- ([1a]-,
R ) H; [1b]-, R ) Me), generated in situ by treatment
In attempts to optimize the reaction conditions of the
above Michael addition, we to discovered that the nature
of the resulting complexes is dramatically affected by
the maximum temperature reached before the acidic
workup. Indeed, once the carbene anions [1]- were
allowed to react with the R,â-unsaturated ketones R1-
(H)CdC(H)C{O}Me (2b-d ) at -78 °C, acidic hydrolysis
carried out at room temperature afforded the 2-cyclo-
hexenone complexes Cp′(CO)2Mn(η2-CHdCHCH(R)CH-
(R1)CH2C{O}) (5, Scheme 1; Table 1, conditions B,
entries 2-4, 6-8).6,9 These complexes were character-
ized by the usual spectroscopic techniques and for some
of them by X-ray diffraction. Complexes 5c, 5d , and 5f
were isolated as single diastereomers, each of them
exhibiting an exo configuration.10 Since partial decom-
position to give paramagnetic species precluded NMR
analysis of the crude reaction mixtures, the formation
n
of Cp′(CO)2MndC(OEt)CH2R (1) with BuLi in THF at
† Email: lugan@lcc-toulouse.fr.
X Abstract published in Advance ACS Abstracts, August 1, 1997.
(1) Wulff, W. D. In Comprehensive Organometallic Chemistry; Abel,
E. W., Stone, F. G. A., Wilkinson, G., Eds.; Elsevier: Oxford, 1995,
Vol. 12, p 469.
(6) The detailed experimental, spectroscopic, and crystallographic
information are provided as Supporting Information.
(7) For a definition of the syn/anti convention used, see: Masamune,
S.; Ali, Sk. A.; Snitman, D. L.; Garvey, D. S. Angew. Chem., Int. Ed.
Engl. 1980, 19, 557.
(2) (a) Wulff, W. D.; Gilbertson, S. R. J . Am. Chem. Soc. 1985, 107,
503. (b) Wulff, W. D.; Anderson, B. A.; Toole, A. J . Am. Chem. Soc.
1989, 111, 5485. (c) Wulff, W. D.; Anderson, B. A.; Toole, A. J .; Xu,
Y.-C. Inorg. Chim. Acta 1994, 220, 215 and references cited therein.
(d) Powers, T. S.; Shi, Y.; Wilson, K. J .; Wulff, W. D. J . Org. Chem.
1994, 59, 6882.
(3) (a) Casey, C. P.; Brunsvold, W. R.; Scheck, D. M. Inorg. Chem.
1977, 16, 3059. (b) Anderson, B. A.; Wulff, W. D.; Rahm, A. J . Am.
Chem. Soc. 1993, 115, 4602. (c) Iyoda, M.; Zhao, L.; Matsuyama, H.
Tetrahedron Lett. 1995, 36, 3699.
(4) Yi, C. S.; Geoffroy, G. L.; White, C. A.; Rheingold, A. L. J . Am.
Chem. Soc. 1993, 115, 3806.
(5) (a) Kelly, C.; Lugan, N.; Terry, M. R.; Geoffroy, G. L.; Haggerty,
B. S.; Rheingold, A. L. J . Am. Chem. Soc. 1992, 114, 6735. (b) Rabier,
A.; Lugan, N.; Mathieu, R.; Geoffroy, G. L. Organometallics 1994, 13,
4676. (c) Gimenez, C.; Lugan, N.; Mathieu, R.; Geoffroy, G. L. J .
Organomet. Chem. 1996, 517, 133.
(8) (a) Assignments of the configurations have been made by 1H
NMR, considering the upfield chemical shift of the substituent gauche
to the phenyl ring for the most stable rotamer (hydrogens anti) in each
diastereomer, see: Oare, D. A.; Heathcock, C. H. J . Org. Chem. 1990,
55, 157. (b) The anti configuration of the Cp analog of anti-3h has been
confirmed by X-ray crystallography; crystal data: monoclinic C2h,5 P21/
c, a ) 15.075(6) Å, b ) 8.766(2) Å, c ) 16.691(2) Å, â ) 111.06(7)°, V
) 2058(2) Å3, Z ) 4, R ) 0.0394, Rw ) 0.0423 for 2171 observations
and 244 variable parameters.
(9) The 2-cyclohexenone complex 5b was originally obtained in 30%
yield upon photolysis of Cp′(CO)3Mn in the presence of 2-cyclohexenone,
see: Giffard, M.; Gentric, E.; Touchard, D.; Dixneuf, P. J . Organomet.
Chem. 1977, 129, 371.
S0276-7333(97)00420-2 CCC: $14.00 © 1997 American Chemical Society

3874 Organometallics, Vol. 16, No. 18, 1997
Communications
Ta ble 1. Rea ction s of Ca r ben e Com p lexes Cp ′(CO)2Mn dC(OEt)CH2R (1) w ith r,â-Un sa tu r a ted Keton es
R1(H)CdC(H)C{O}R2 (2)
carbene
R,â-unsaturated ketone
R1 R2
Ph
conditions Aa
yieldc
conditions Bb
yieldc
entry
R
product(s)
anti/synd
product(s)
cis/transe,f
1
2
3
4
5
6
7
8
1a
1b
H
H
H
H
Me
Me
Me
Me
2a
2b
2c
2d
2a
2b
2c
2d
Ph
3a
3b
3c
3d g
3e
3f
98
66
88
85
85
61
82
94
H
Me
Me
Me
Ph
Me
Me
Me
5b
5c
5d
66
65
49
Me
Ph
Ph
H
66:34
5f
5g
5h
59
69
90
Me
Ph
3g
3h
75:25
85:15
80:20
91:9
a
Conditions A: the carbene anion [1]- was generated in situ by reaction of 1 with 1.1 equiv of nBuLi at -78 °C in THF, and after 20
min, 1.1 equiv of R,â-unsaturated ketone was added. After 15 min, the reaction was quenched by the addition of a saturated solution of
b
NH4Cl. Conditions B: as in conditions A, except after the addition of the R,â-unsaturated ketone the reaction medium was allowed to
reach room temperature, stirred for 2 h, and then the reaction was quenched by the addition of a saturated solution of NH4Cl. c Isolated
overall yield. Estimated by 1H NMR on crude reaction mixtures after a short filtration on alumina. e cis/trans refers to the relative
d
position of the R and R1 substituents within the cyclohexenone ring. f Ratio of isolated complexes after chromatographic workup. 1,2-
g
Addition product formed in trace amounts (<5%).
Sch em e 1
20 ratios, respectively. The structure of the major
stereoisomer of cis-5h has been determined by X-ray
crystallography: 12 the methyl and phenyl substituents
within the cyclohexenone ring are found in a relative
cis position, and the Cp′(CO)2Mn fragment is coordi-
nated onto the opposite face. The configuration of the
minor species trans-5g and trans-5h could not be fully
3
elucidated, although the observed J HH of 9.1 and 10.1
Hz, respectively, between the protons of the adjacent
CH(R) and CH(R1) groups within the cyclohexenone ring
indicate a relative trans position for the R and R1
substituents in each complex.
Scheme 2 illustrates a possible mechanism for 5h that
would account for the unexpected formation of cyclo-
hexenone complexes 5. Nucleophilic attack of the
carbene anion [1b]- on benzylideneacetone 2d would
give the anti enolate anion [anti-3h ]- as the major
diastereomer. According to Casey et al., related types
of enolate anions generated from chromium carbene
complexes readily equilibrate in favor of the correspond-
ing carbene anions.3a Such a process would not pre-
dominate in the present case due to the destabilizing
effect of the Cp′(CO)2Mn fragment toward carbene
anions. Instead, a small portion of [anti-3h ]- would
isomerize to give the terminal enolate, allowing an
intramolecular nucleophilic substitution for the ethoxy
group on the carbene carbon to take place upon warming
to room temperature, thus producing [6h ]-,13 in which
the 4-Me and 5-Ph substituents are in a cis position, as
found in the major final product cis-5h . The acidic
hydrolysis of [6h ]- would lead to the neutral carbene
complex 8h , from which a final 1,2-hydride shift14 would
produce the cyclohexenone complex cis-5h . (Similarly,
the minor cyclohexenone complex trans-5h would be
produced from the minor syn enolate anion [6h -syn]-,
not represented on Scheme 2.)
of the endo isomers cannot be excluded.11 The disub-
stituted 2-cyclohexenone complexes 5g and 5h were
isolated as two of four potential diastereomers cis-5g
and trans-5g and cis-5h and trans-5h in 78:22 and 80:
5
(10) Crystal data for 5d : monoclinic C2h
,
P21/n, a ) 9.516(2) Å, b
As it can now be expected, cyclohexenone complexes
5 can be alternatively obtained from the corresponding
) 14.691(3) Å, c ) 12.447(3) Å, â ) 105.26(2)°, V ) 1678.7(7) Å3, Z )
4, R ) 0.0262, Rw ) 0.0296 for 2088 observations and 217 variable
parameters. Crystal data for 5f: triclinic Ci,1 P1, a ) 6.826(3) Å, b )
9.506(1) Å, c ) 11.789(2) Å, R ) 69.23(1)°, â ) 86.65(3)°, γ ) 74.21-
(3)°, V ) 687.6(4) Å3, Z ) 2, R ) 0.0383, Rw ) 0.0443 for 1805
observations and 172 variable parameters.
5
(12) Crystal data for cis-5h : monoclinic C2h
,
P21/n, a ) 10.022(1)
Å, b ) 7.067(2) Å, c ) 25.551(3) Å, â ) 90.65(1)°, V ) 1809.5(5) Å3, Z
) 4, R ) 0.0543, Rw ) 0.0623 for 1055 observations and 166 variable
parameters.
(11) Column chromatography of freshly prepared 5 on alumina
shows a relatively fast moving band containing an extremely air-
sensitive unidentified purple complex, along with traces of the corre-
sponding free cyclohexenone. As this phenomenon disappears upon
repeated chromatographic workup, we suspect it might be due to a
selective decomposition of unstable stereoisomers. In few instances,
after a first purification, traces of another complex could be observed
along with 5d , the 13C NMR spectrum of which may correspond to the
endo stereoisomers.6
(13) At this stage, IR spectroscopy does indicate the formation of
an anionic carbene complex (IR νCO (THF): 1897, 1830 cm-1). Further
evidence for the nature of the elusive intermediate [6h ]- was obtained
by a methylation reaction leading to the fully characterized cyclic
vinylcarbene 7h .6
(14) (a) Casey, C. P.; Brunsvold, W. R. Inorg. Chem. 1977, 16, 391.
(b) Roger, C.; Bodner, G. S.; Hatton, W. G.; Gladysz, J . A. Organome-
tallics 1991, 10, 3266 and references cited therein.

Communications
Organometallics, Vol. 16, No. 18, 1997 3875
Sch em e 2
Ta ble 2. F or m a tion of Cycloh exen on e Com p lexes
5 fr om Mich a el Ad d u cts 3a a n d Dem eta la tion
Rea ction sb
We are now currently attempting to elucidate the
factors which govern the diastereoselectivity of the
initial nucleophilic attack of prochiral manganese car-
bene anions on Michael acceptors, as well as to explore
further possibilities to functionalize the cyclohexenone
ring within diastereomerically pure substituted cyclo-
hexenone complexes.
complex 3
R1 R2
Me 5b
complex 5
yield
90 9b
59 9c
cyclohexenone 9
entry
R
yieldc
1
2
3
4
5
6
7
8
3b
3c
3d
3f
H
H
77
82
92
80
75
78
86
88
H
H
Me Me 5c
Ph Me 5d
49 9d
95 9f
72 cis-9g
77 trans-9g
87 cis-9h
70 trans-9h
Me
H
Me 5f
anti-3g Me Me Me cis-5g
syn-3g Me Me Me trans-5g
anti-3h Me Ph Me cis-5h
syn-3h Me Ph Me trans-5h
Ack n ow led gm en t. We thank the CNRS for finan-
cial support, the French Ministe`re de l’Education Na-
tionale, de l’Enseignement Supe´rieur et de la Recherche
Scientifique for a fellowship to C.M., and Dr. Guy
Lavigne for helpful discussion.
a
LDA (1.1 equiv) was added at -78 °C to a solution of complex
3 in THF. The reaction medium was allowed to reach room
temperature. After 2 h, the reaction was quenched by the addition
b
of a saturated solution of NH4Cl. Triphenylphosphine (1.5 equiv)
Su p p or tin g In for m a tion Ava ila ble: Text giving experi-
mental and spectroscopic data for all the new complexes and
full experimental data for the X-ray studies, tables of atomic
coordinates, anisotropic temperature factors, and bond dis-
tances and angles for anti-3h (Cp analog), 5d , 5f, and cis-5h ,
and figures showing perspective views of complexes anti-3h
(Cp analog), 5d , 5f, and cis-5h (39 pages). Ordering informa-
tion is given on any current masthead page.
was added to a solution of cyclohexenone complex 5, and the
mixture was heated under reflux until total disapperance (by IR)
of 5 (2 h). c Isolated yieds after chromatographic workup on
alumina.
Michael adducts 3 upon treatment with LDA at -78 °C
and subsequent acidic hydrolysis at room temperature
(Scheme 1; Table 2).6 Complexes cis-5g or trans-5g and
cis-5h or trans-5h can, thus, be selectively obtained from,
respectively, the separated anti or syn diastereomers of
3g and 3h (Table 2, entries 5-8).
Finally, the overall reaction sequence represented on
Scheme 1 could be of synthetic use since 2-cyclohex-
enones 9 can easily be released upon treatment of the
type 5 complexes either with triphenylphosphine in
refluxing THF15 or under a moderate pressure (4 atm)
of carbon monoxide (Table 2).16 It is noteworthy that
this is the first diastereoselective synthesis of the 4,5-
disubstituted 2-cyclohexenones 9g17 and 9h 18 reported
so far.19,20
OM9704206
(17) (a) Kugatova-Shemyakina, G. P.; Lutsenko, V. V. Izv. Akad.
Nauk SSSR, Ser. Khim. 1962, 8, 1429. (b) For the use of cis/trans-
4,5-dimethyl 2-cyclohexenone as a flavoring agent, see: Flament, I.
Fr. Pat. Appl. 73.28312, 1973.
(18) The synthesis of 5-phenyl-4-methyl 2-cyclohexenone (9h ) as a
cis/trans mixture has only recently been reported, see: Aurell, M. J .;
Gavin˜a, P.; Mestres, R. Tetrahedron 1994, 50, 2571.
(19) For other metal-mediated stoichiometric syntheses of 2-cyclo-
hexeneones, see, for instance: (a) Mortimer, M. D.; Carter, J . D.;
McElwee-White, L. Organometallics 1993, 12, 4493. (b) McDaniel, K.
F.; Kracker, L. R., II; Thamburaj, P. K. Tetrahedron Lett. 1990, 31,
2373. (c) Potter, G. A.; McCague, R. J . J . Chem. Soc., Chem. Commun.
1990, 1172. (d) Muzart, J .; Pale, P.; Pete, J .-P. J . Chem. Soc., Chem.
Commun. 1981, 668. (e) Birch, A. J .; Pearson, A. J . J . Chem. Soc.,
Chem. Commun. 1976, 601.
(15) (a) Angelici, R. J .; Loewen, W. Inorg. Chem. 1967, 6, 682. (b)
Schinzer, D.; Blume, T.; Rojas Wahl, R. U. Synlett 1994, 297.
(16) This procedure yields Cp′Mn(CO)3 as the only organometallic
“byproduct”, which may be recycled to regenerate 1.
(20) For relevent syntheses in terms of bond disconnections of
substituted 2-cyclohexenones, see for instance: (a) Yamada, S.-I.;
Otani, G. Tetrahedron Lett. 1969, 4237. (b) Ito, Y.; Sawamura, M.;
Kominami, K.; Saegusa, T. Tetrahedron Lett. 1985, 26, 5303.-