New oxidative demetalation protocol for molybdenum π-complexes: Enantiocontrolled synthesis of unsaturated ketones and lactones

Article abstract of DOI:10.1021/jo020002x

An efficient and general oxidative demetalation of (η³-allyl)molybdenum complexes using pyridinium dichromate allows the introduction of a carbonyl group at an allylic terminus of the π-system. The process takes place with high regiocontrol and can lead to the preparation of unsaturated ketones and lactones of high enantiopurity.

Full text of DOI:10.1021/jo020002x

New Oxid a tive Dem eta la tion P r otocol for Molybd en u m
π-Com p lexes: En a n tiocon tr olled Syn th esis of Un sa tu r a ted
Keton es a n d La cton es
Ana Alcudia, Ramo´n Go´mez Arraya´s, and Lanny S. Liebeskind*
Department of Chemistry, Emory University, 1515 Pierce Drive, Atlanta, Georgia 30322
chemLL1@emory.edu
Received J anuary 2, 2002
An efficient and general oxidative demetalation of (η3-allyl)molybdenum complexes using pyridinium
dichromate allows the introduction of a carbonyl group at an allylic terminus of the π-system. The
process takes place with high regiocontrol and can lead to the preparation of unsaturated ketones
and lactones of high enantiopurity.
In tr od u ction
which, after simple oxidation (air, ceric ammonium
nitrate), afforded the corresponding R-functionalized
olefins. Mo complexes carrying a pendant nucleophilic
group undergo regiocontrolled, intramolecular nucleo-
philic addition using this protocol.1b,8c,11,12 NO+-based
decomplexation protocols have also been extended to
analogous TpMo(CO)2(π-allyl) [Tp ) hydridotris(1-pyra-
zolyl)borate] complexes, where oxidative decomplexation
of the intermediate η2-alkene complex occurs spontane-
ously.1c,d,f,12
The ability of stoichiometric (η3-allyl)molybdenum
complexes of high enantiopurity to participate in multiple
and sequential, regio- and stereocontrolled bond con-
structions render them potent chiral scaffolds for the
asymmetric synthesis of complex organic molecules.1
Given the efficient preparation and ease of manipulation
of these air-stable, solid organometallic intermediates,
their synthetic potential depends on efficient and general
methods for decomplexation/functionalization that occur
with high regio- and stereoselectivity.
A variety of demetalation protocols are known. In 1976
Faller reported that CpMo(CO)2(η3-allyl) (Cp ) η5-cyclo-
pentadienyl) complexes are easily converted to allyl
cation equivalents by replacement of one CO ligand with
NO+ using NOBF4.2,3 Treatment of the resulting [CpMo-
(CO)(NO)(π-allyl)]+ cations with nucleophiles such as
hydride,4 deuteride,5 hydroxyl,4,5,6 enamines,5b,7 thio-
lates,4,8 dithiocarbamate,5 malonate,7b,9 and organocu-
prates1h,9a,10 gave the corresponding η2-alkene complexes
In 1985 Pearson reported the decomplexation of CpMo-
(CO)2(π-allyl) complexes by treatment with iodine13 or
bromine.14 Iodo (or bromo) alkenes are formed by addition
(5) (a) Faller, J . W.; Chao, K. H.; Murray, H. H. Organometallics
1984, 3, 1231-1240. (b) Faller, J . W.; Chao, K.-H. J . Am. Chem. Soc.
1983, 105, 3893-3898.
(6) Faller, J . W.; Chao, K.-H. Organometallics 1984, 3, 927-932.
(7) (a) Faller, J . W.; Lambert, C. Tetrahedron 1985, 41, 5755-5760.
(b) Faller, J . W.; Lambert, C.; Mazzieri, M. R. J . Organomet. Chem.
1990, 383, 161-177.
(8) (a) Liao, M.-F.; Lee, G.-H.; Peng, S.-M.; Liu, R.-S. Organometal-
lics 1994, 13, 4973-4977. (b) Yeh, M.-C. P.; Tsou, C.-J .; Cuang, C.-N.;
Lin, H.-C. J . Chem. Soc., Chem. Commun. 1992, 890-891. (c) Wang,
S.-H.; Cheng, Y.-C.; Lee, G.-H.; Peng, S.-M.; Liu, R.-S. Organometallics
1993, 12, 3282-3290.
(9) (a) Yu, R. H.; McCallum, J . S.; Liebeskind, L. S. Organometallics
1994, 13, 1476-1486. (b) Hansson, S.; Miller, J . F.; Liebeskind, L. S.
J . Am. Chem. Soc. 1990, 112, 9660-9661.
(10) (a) Christopher, J . A.; Kocienski, P. J .; Procter, M. J . Synlett.
1998, 425-427. (b) Kocienski, P. J .; Brown, R. C. D.; Pommier, A.;
Procter, M.; Schmidt, B. J . Chem. Soc., Perkin Trans. 1 1998, 9-39.
(11) (a) Lin, S.-H.; Lush, S.-F.; Cheng, W.-J .; Lee, G.-H.; Peng, S.-
M.; Liao, Y.-L.; Wang, S.-L.; Liu, R.-S. Organometallics 1994, 13, 1711-
1719. (b) Lin, S.-H.; Cheng, W.-J .; Liao, Y.-L.; Wang, S.-L.; Lee, G.-H.;
Peng, S.-M.; Liu, R.-S. J . Chem. Soc., Chem. Commun. 1993, 1391-
1393. (c) Yeh, M.-C.; Chaung, C.-N. J . Chem. Soc., Perkin Trans. 1
1996, 2167-2172.
* Corresponding author. Fax: 404-727-0845.
(1) For a recent review, see: (a) Li, C.-L.; Liu, R.-S. Chem. Rev. 2000,
100, 3127-3161. For recent examples, see also: (b) Pearson, A. J .;
Mesaros, E. F. Org. Lett. 2002, 4, 2001-2004. (c) Shu, C.; Alcudia, A.;
Yin, J .; Liebeskind, L. S. J . Am. Chem. Soc. 2001, 123, 12477-12487.
(d) Arraya´s, R. G.; Liebeskind, L. S. J . Am. Chem. Soc. 2001, 123,
6185-6186. (e) Yin, J .; Llorente, I.; Villanueva, L. A.; Liebeskind, L.
S. J . Am. Chem. Soc. 2000, 122, 10458-10459. (f) Moretto, A. F.;
Liebeskind, L. S. J . Org. Chem. 2000, 65, 7445-7455. (g) Malinakova,
H. C.; Liebeskind, L. S. Org. Lett. 2000, 2, 4083-4686. (h) Christopher,
J . A.; Kocienski, P. J .; Kuhl, A.; Bell, R. Synlett. 2000, 463.
(2) (a) Faller, J . W.; Rosan, A. M. J . Am. Chem. Soc. 1976, 98, 3388-
3389. (b) Faller, J . W.; Rosan, A. M. J . Am. Chem. Soc. 1977, 99, 4858.
See also: (c) Cosford, N. D. P.; Liebeskind, L. S. Organometallics 1994,
13, 1498-1503.
(12) The first general description of synthetically useful transforma-
tions of TpMo(CO)2(η3-allyl) and TpMo(CO)2(η4-diene) complexes is
documented within the Supporting Information for: (a) Ward, Y. D.;
Villanueva, L. A.; Allred, G. D.; Liebeskind, L. S. J . Am. Chem. Soc.
1996, 118, 897-898. See also: (b) Pearson, A. J .; Douglas, A. R.
Organometallics 1998, 17, 1446-1448. (c) Yin, J .; Liebeskind, L. S. J .
Am. Chem. Soc. 1999, 121, 5811-5812 and references 1c,d,f.
(13) (a) Pearson, A. J .; Khan, M. N. I.; Clardy, J . C.; Cun-Heng, H.
J . Am. Chem. Soc. 1985, 107, 2748-2757. (b) Pearson, A. J .; Khan,
M. N. I. J . Org. Chem. 1985, 50, 5276-5285.
(3) Faller also described that nucleophilic (π-allyl)Mo(NO)(X)Cp
(X ) halide) complexes, easily prepared from [(π-allyl)Mo(CO)(NO)-
Cp]+ by treatment with LiX, reacted with aldehydes to give demeta-
lated secondary homoallylic alcohols stereospecifically in high yields.
However, this three-step demetalation protocol has been used only with
few acyclic Mo complexes: (a) Faller, J . W.; Nguyen, J . T.; Ellis, W.;
Mazzieri, M. R. Organometallics 1993, 12, 1434-1438 and references
therein. See also: (b) Vong, W.-J .; Peng, S.-M.; Lin, S.-H.; Lin, W.-J .;
Liu, R.-S. J . Am. Chem. Soc. 1991, 113, 573-582.
(4) Adams, R. D.; Chodosh, D. F.; Faller, J . W.; Rosan, A. M. J . Am.
Chem. Soc. 1979, 101, 2570-2578.
(14) Pearson, A. J .; Mallik, S.; Mortezaei, R.; Perry, M. W. D.;
Shively, R. J .; Youngs, W. J . J . Am. Chem. Soc. 1990, 112, 8034-8042.
10.1021/jo020002x CCC: $22.00 © 2002 American Chemical Society
Published on Web 07/11/2002
J . Org. Chem. 2002, 67, 5773-5778
5773

Alcudia et al.
of halide to the intermediate cationic [CpMo(CO)(X)(η3-
allyl)]+ complex, trans to the metal.15 Poor regiocontrol
results with unsymmetrically substituted η3-allyl com-
plexes.13a,16 When combined with suitable nucleophiles,
iodo and bromo demetalations provide access to nucleo-
philic substitution products that are conceptually related
to the CO/NO+ ligand exchange protocol.13b,17 Complexes
containing a pendant nucleophile such as a carboxylate13
or hydroxyl group18 produce cyclization products with
high regio- and stereocontrol.
SCHEME 1
SCHEME 2
Protodemetalation of Cp and Tp (η3-allyl)molybdenum
complexes has also been achieved with TFA,9b,12c,19 AcOH/
hν,1c,e or HCl1c,9b and affords the corresponding alkenes.
Direct oxidative decomplexations are also known.
Pearson described an oxidative method for the direct
decomplexation of CpMo(CO)2(π-allyl) complexes accom-
panied by introduction of an OH group.13a In a related
transformation, cyclic Mo complexes bearing a methoxy
group1f,g,20 at a terminus of the π-allylic system have been
oxidatively demetalated with ceric ammonium nitrate or
CuCl2 to afford the corresponding R,â-unsaturated ke-
tones.21,22 As a complement to the preceding demetalation
procedures, we report herein a novel, efficient, and
general oxidative demetalation of (η3-allyl)molybdenum
complexes that allows the introduction of a carbonyl
group at an allylic terminus of the π-system. The process
takes place with high regiocontrol and leads to unsatur-
ated ketones and lactones. High enantiopurity (η3-allyl)-
molybdenum complexes lead to high enantiopurity un-
saturated ketones and lactones.
Oxidation of η3-allyl systems bearing a terminal elec-
tron-donating alkoxy substituent occurs at the alkoxy-
substituted terminus. For example, the 4-methoxytet-
rahydropyridinyl-Mo complex 1027 was oxidatively
demetalated to the tetrahydropyridone 1128 in 81% yield
and with complete regiocontrol (Scheme 2).
Related alkoxy-directed oxidative demetalations led to
the synthesis of the R,â-unsaturated lactones shown in
Scheme 3 and Table 1. A range of variously substituted
(η-2,3,4-pyranyl)molybdenum (12, 13)29 and (η-2,3,4-
chromenyl)molybdenum complexes (16-20)30 were con-
(25) Compounds 2 and 3 were prepared by following the synthetic
sequence shown below (see Supporting Information for details).
3-(Acetyloxy)-1-(ethoxycarbonyl)-1,2,3,6-tetrahydropyridine (I) was pre-
pared by following a previously described procedure: (a) Imanishi, T.;
Shin, H.; Hanaoka, M.; Momose, T.; Imanishi, I. Chem. Pharm. Bull.
1982, 30, 3617-3623. (b) Imanishi, T.; Imanishi, I.; Momose, T. Synth.
Commun. 1978, 8, 99-102.
Resu lts a n d Discu ssion
When various non-electron-deficient carbocyclic and
heterocyclic (η3-allyl)molybdenum complexes were treated
with pyridinium dichromate (PDC)/silica gel,23 demeta-
lations occurred concurrent with oxidation of a terminal
position of the π-system. The corresponding R,â-unsatur-
ated ketones were obtained in good yields (Scheme 1).24
Unsymmetrically substituted complexes (325 and 526) gave
enones in good yields with the carbonyl group situated
at the sterically less hindered terminal position of the
allylic system.
(26) Molybdenum complex 5 was prepared from 5-bromo-5,6-dihy-
dro-2H-pyran-2-one, II, as shown below (see Supporting Information
for experimental details and characterization data). For the synthesis
of (+)-4, (-)-4, and (+)-III, see ref 12a. For the synthesis of II, see:
Nakagawa, M.; Saegusa, J .; Tonozuka, M.; Obi, M.; Kiuchi, M.; Hino,
T.; Ban, Y. Org. Synth. 1977, 56, 49.
(15) When the anti attack of iodide is sterically disfavored, the metal
can deliver the iodo intramolecularly to the face of the π-ligand syn to
the molybdenum (see ref 12c).
(16) Chou, S.-S. P.; Sheng, H.-T. Organometallics 1996, 15, 4113-
4115.
(17) Bjurling, E.; J ohansson, M. H.; Andersson, C.-M. Organome-
tallics 1999, 5606-5613.
(18) Liao, M. F.; Lee, G.-H.; Peng, S.-M.; Liu, R.-S. Organometallics
1994, 14, 4973.
(19) Rubio, A.; Liebeskind, L. S. J . Am. Chem. Soc. 1993, 115, 891-
901.
(20) Malinakova, H.; Liebeskind, L. S. Org. Lett. 2000, 2, 3909-
3911.
(21) Birch has also reported the transformation of functionalized
tricarbonyl(3-methoxycyclohexa-2,4-dien-1-yl)iron complexes into de-
metalated 5-substituted-2-cyclohexenones using J ones’ reagent or
PCC: (a) Kelly, L. F.; Dahler, P.; Narula, A. S.; Birch, A. J . Tetrahedron
Lett. 1981, 22, 1433-1436. See also: (b) Pearson, A. J .; Khetani, V.
D.; Roden, B. A. J . Org. Chem. 1989, 54, 5141-5147.
(22) Mo complexes bearing a methyl substituent at an allyl terminus
of the π-system can also be demetalated with CAN/Et3N to afford a
diene (see ref 12c).
(27) Molybdenum complex 10 was prepared from 11 by following
the one-pot sequence shown (see Supporting Information for experi-
mental details and characterization data):
(23) For the use of PCC-silica gel system for oxidation of alcohols
to carbonyl compounds, see: Adams, L. L.; Luzzio, F. A. J . Org. Chem.
1989, 54, 5387-5390.
(24) For synthesis and characterization data for the molybdenum
complex 1, see: McCallum, J . S.; Sterbenz, J . T.; Liebeskind, L. S.
Organometallics 1993, 12, 927-932.
(28) For previous synthesis of 11, see: (a) Comins, D. L.; Chung,
G.; Foley, M. A. Heterocycles 1994, 37, 1121-1140. (b) Comins, D. L.;
Foley, M. A. Tetrahedron Lett. 1988, 29, 6711-6714.
5774 J . Org. Chem., Vol. 67, No. 16, 2002

Oxidative Demetalation Protocol for Mo π-Complexes
TABLE 1. Oxid a tive Dem eta la tion of (η3-Allyl)m olybd en u m Com p lexes
cmpd
product
R1
R2
R3
R4
%
ee (%)a
(-)-16b
(-)-17b
(-)-18c
(()-19
(()-20
(+)-21
(+)-22
(+)-23
(()-24
(()-25
CO2Me
COMe
CHO
CHO
-CON(Me) CO-
H
H
H
H
H
H
n-Bu
Me
H
H
H
H
Me
H
85
80
72
70
60
98
98
99.8
a
b
Measured by chiral HPLC. 98% ee. c 99.8% ee.
SCHEME 3
SCHEME 5
underwent oxidative demetalation as efficiently as its Tp
analogue (+)-26.
SCHEME 4
No racemization was observed in the demetalation of
the enantiomerically pure Mo complexes 26-28, pre-
pared from D-glucose. Lactone (-)-31 was transformed
into (+)-5-(hydroxymethyl)-δ-valerolactone, (+)-32, a ver-
satile intermediate in Corey’s synthesis of leukotriene B
(Scheme 5).31i,34
The mechanism of this oxidative demetalation must
accommodate the disparate demetalation paths followed
by the electron-deficient and non-electron-deficient (η3-
allyl)molybdenum complexes and account for the ob-
served regioselectivities. Oxidation of the non-electron-
deficient (η3-allyl)molybdenum complexes by PDC would
generate a cationic allylmolybdenum (Scheme 6). Those
η3-allyl complexes with a directly attached electron-
donating substituent should suffer addition of water anti
to the TpMo(CO)2 moiety and adjacent to the electron-
donating substituent; for those not bearing an electron-
donating substituent, the incoming water would be
verted into the corresponding 5,5-disubstituted dihydro-
pyranones and tetrahydrochromen-2-ones (21-25),30
respectively, in good yields. These combined results
demonstrate the compatibility of this method with vari-
ous functional groups.
In contrast to the PDC/silica gel mediated oxidation
of non-electron-deficient (η3-allyl)molybdenum complexes,
treatment of electron-deficient (η3-allyl)molybdenum com-
plexes with PDC/silica gel (CH2Cl2, room temperature,
24 h) followed a protodemetalation course. As shown in
Scheme 4, three different â,γ-unsaturated lactones (29-
31)31 were obtained in good yields32 from the correspond-
ing lactonylmolybdenum complexes (4 and 26-28)33
using the PDC/SiO2 protocol. Surprisingly, no aldehyde
was detected by NMR analysis of the crude reaction
mixture of (-)-31. The hydridotris(pyrazolyl)borate ligand
(Tp) does not seem to be a requirement for the success of
this procedure, since (+)-2719 (Cp ) cyclopentadienyl)
(31) For previous syntheses of 29, see: (a) Hattori, T.; Suzuki, Y.;
Uesugi, O.; Shuichi, O.; Miyano, S. Chem. Commun. 2000, 73-74. (b)
Yamada, S.; Matsumoto, M. Chem. Lett. 1992, 2273-2276. (c) Smadja,
W.; Zahouily, M.; Malacria, M. Tetrahedron Lett. 1992, 33, 5511-5514.
(d) Stensen, W.; Svedsen, J . S.; Hofer, O.; Sydnes, L. K. Acta Chem.
Scand., Ser. B 1988, B42, 259-268. (e) Suzuki, M.; Takada, H.; Noyori,
R. J . J . Org. Chem. 1982, 47, 902-904. (f) Nakashima, Y.; Imagawa,
T.; Kawanisi, M. Synth. Commun. 1979, 9, 889-894. (g) Aumann, R.;
Ring, H.; Krueger, C.; Goddard, R. Chem. Ber. 1979, 112, 3644-3671.
(h) Bonjouklian, R.; Ruden, R. A. J . Org. Chem. 1977, 42, 4095-40103.
Only one synthesis of (-)-30 has been described: (i) Corey, E. J .; Pyne,
S. G.; Su, W. G. Tetrahedron Lett. 1983, 24, 4883-4886.
(32) The moderate isolated yield of 29 was attributed to its low
boiling point.
(33) Compound (+)-28 was obtained from (+)-26 (ref 12a) after basic
hydrolysis of the acetate [LiOH, EtOH, room temperature, 97% (see
Supporting Information for details)]. For the synthesis of (+)-27, see
ref 19.
(29) Mo complexes 12 (ref 1d) and 13 (see Supporting Information
for experimental details and characterization data) were prepared from
IV (ref 12c) as shown:
(34) For previous enantioselective syntheses of (+)-32, see: (a) Liu,
Z.-Y.; J i, J .-X.; Li, B.-G. J . Chem. Soc., Perkin Trans. 1 2000, 3519-
3521. (b) Coutrot, Ph.; Grison, C.; Bomont, C. Tetrahedron Lett. 1994,
35, 8381-8384. (c) Lees, W. J .; Whitesides, G. M. J . Org. Chem. 1993,
58, 1887-1894. (d) Sugita, Y.; Sakaki, J .; Sato, M.; Kaneko, C. J . Chem.
Soc., Perkin Trans. 1 1992, 2855-2861. (e) Blaser, F.; Deschenaux, P.
F.; Kallimopoulos, T.; Gacot-Guillarmod, A. Helv. Chim. Acta 1991,
74, 141-145. (f) Leggeri, P.; Azzolina, O.; Pirillo, D.; Traverso, G.
Farmaco 1989, 44, 303-313. (g) Pianetti, P.; Pougny, J . R. J .
Carbohydr. Chem. 1988, 7, 811-815. (h) Gerth, D. B.; Giese, B. J . Org.
Chem. 1986, 51, 3726-3729.
(30) The oxidative demetalation of molybdenum complexes 16-19
was previously communicated (ref 1d). A complete description of the
synthesis and characterization data for compounds 16-19 is found
within the Supporting Information for ref 1d. For synthesis and
characterization data for compound 20, see the Supporting Information.
J . Org. Chem, Vol. 67, No. 16, 2002 5775

Alcudia et al.
SCHEME 6
(()-1-(E t h o x y c a r b o n y l)-1,2,3,6-t e t r a h y d r o -3-p y r i-
d on e (7).25a-b,38 Following the general procedure, 2 (250 mg,
0.48 mmol) was demetalated to afford, after chromatographic
purification (4:1 n-hexanes-EtOAc), the known 7 (56.7 mg,
70%) as a colorless oil. 1H NMR (CDCl3, 400 MHz): δ 7.03 (m,
1H), 6.16 (dt, J ) 10.2, 2.2 Hz, 1H), 4.27 (m, 2H), 4.16 (q, J )
7.0 Hz, 2H), 4.14 (s, 2H), 1.26 (t, J ) 7.0 Hz, 3H).
SCHEME 7
(()-1-(Eth oxyca r bon yl)-6-ben zyl-1,2,5,6-tetr a h yd r o-3-
p yr id on e (8). Following the general procedure, 3 (248 mg,
0.4 mmol) was demetalated to afford, after chromatographic
purification (11:1 n-hexanes-EtOAc), 8 (77.2 mg, 73%) as a
colorless oil. TLC (7:1 n-hexanes-EtOAc): Rf ) 0.4. IR (neat,
cm-1): 2934 (br), 2860 (w), 1737 (s), 1698 (s), 1428 (w), 1374
(m), 1336 (w), 1243 (s), 1173 (w), 1108 (w), 1077 (w), 1023 (m),
980 (w). 1H NMR (50:50 mixture of rotamers): δ 7.34-7.14
(m, 5H), 6.90 (dd, J ) 10.2, 4.8 Hz, 1H), 6.12 (d, J ) 4.8 Hz,
1H), 5.07 (bs, 0.5 H), 4.95 (bs, 0.5 H), 4.67 (bd, J ) 19.5 Hz,
0.5H), 4,49 (bd, J ) 18.4 Hz, 0.5H), 4.24-3.98 (m, 2H), 3.64-
3.46 (m, 1H), 3.08-2.95 (m, 2H), 1.24 (m, 3H). 13C NMR
(CDCl3, 100 MHz): δ 192.9, 155.0, 150.5, 149.6, 136.4, 129.5,
128.9, 127.3, 127.1, 70.6, 70.3, 62.2, 53.9, 53.4, 49.5, 48.9, 39.0,
directed to the sterically least hindered η3-allyl terminus.
In both cases the intermediate allylic alcohols would be
oxidized to enones by the excess PDC.
Electron-deficient (η3-allyl)molybdenum complexes 4
and 26-28 followed an unexpected oxidation-induced
protodemetalation path (Scheme 7).35 This can be ratio-
nalized by the presumed tendency of the electron-
deficient (η3-allyl)molybdenum complexes to undergo an
η3 η1 slippage, particularly after oxidation of Mo by PDC
diminishes stabilization of the η3 form through back-
bonding. The η1-molybdenum dienolate should then
undergo a well-established kinetic R-protonation.
38.5, 29.9, 29.5, 22.9, 14.7. HRMS (FAB): calcd for C15H17
-
NO3Li [M++Li], 259.1208; found, 259.1204.
Con clu sion s
(()-2-P h en yl-5,6-d ih yd r o-2H-p yr a n -3-on e (9). Following
the general procedure, 5 (460 mg, 0.85 mmol) was demetalated
to afford, after chromatographic purification (1:2 n-hexanes-
CH2Cl2), 9 (120 mg, 75%) as a colorless oil. TLC (1:2 n-hex-
anes-CH2Cl2 1:2): Rf ) 0.15. IR (neat, cm-1): 3034 (w), 2822
An efficient and general procedure for the demetalation
of molybdenum π-complexes using pyridinium dichro-
mate is reported. The reaction with non-electron-deficient
(η3-allyl)molybdenum complexes allows the introduction
of a carbonyl group at an allylic terminus of the π-system,
while electron-deficient complexes undergo an oxidation-
induced protodemetalation. In both cases the process
takes place with good yields and high regiocontrol and
leads to the preparation of unsaturated ketones and
lactones of high enantiopurity.
1
(w), 1695 (s), 1258 (m), 1096 (m). H NMR (CDCl3, 400 MHz):
δ 7.42-7.37 (m, 5 H), 7.12 (dd, J ) 10.5, 2.2 Hz, 1H), 6.28 (dd,
J ) 10.5, 2.2 Hz, 1H), 5.39 (m, 1H), 4.32 (d, J ) 16.3, Hz, 1H),
4.25 (dd, J ) 16.3, 1.6 Hz, 1H). 13C NMR (CDCl3, 100 MHz):
δ 194.3, 150.6, 137.7, 128.9, 128.8, 127.4, 126.9, 75.8, 70.9.
HRMS [M+]: calcd for C11H10O2, 174.0681; found, 174.0673.
(()-1-((P h en yloxy)ca r bon yl)-1,2,3,4-tetr a h yd r o-4-p yr i-
d on e (11).28 Following the general procedure, 10 (450 mg, 0.75
mmol) was demetalated to afford, after chromatographic
purification (8:1 n-hexanes-EtOAc), 11 (132 mg, 81%) as a
colorless oil. TLC (4:1 n-hexanes-EtOAc 4:1): Rf ) 0.4. IR
(neat, cm-1): 2362 (br), 2343 (br), 1741 (s), 1671 (s), 1602 (s),
1420 (w), 1351 (m), 1332 (m), 1305 (s), 1200 (s), 1181 (s), 1081
Exp er im en ta l Section 36
Gen er a l P r oced u r e for th e Dem eta la tion w ith P DC.
To a solution (or suspension) of the molybdenum complex (0.20
mmol) in CH2Cl2 (2.0 mL) was added a mixture of PDC (241
mg, 0.64 mmol) and silica gel (241 mg, 0.64 mmol) in one
portion as a solid. The mixture was stirred at room temper-
ature for 12-20 h. It was then passed through a short pad of
Celite with a thin layer of silica gel on the top (eluted with
2:1 CH2Cl2-EtOAc). After concentration, the residue was
purified by flash chromatography to afford the corresponding
pure demetalated product.
1
(w), 984 (w), 810 (w), 748 (w), 690 (w). H NMR (CDCl3, 400
MHz): δ 8.97 (d, J ) 7.9 Hz, 1H), 7.44-7.15 (m, 5H), 5.60-
5.39 (bs, 1H), 4.21-4.00 (bs, 2H), 2.75-2.50 (m, 2H). 13C NMR
(CDCl3, 100 MHz): δ 193.1, 150.3, 143.4, 142.6, 129.6, 126.4,
121.2, 108.3, 77.3, 77.0, 76.6, 42.7, 35.6. HRMS (FAB): cald
for C12H11N1O3 [M+], 217.0743; found, 217.0739. Anal. Calcd
(()-5,5-Dim eth ylh ex-2-en -1-on e (6).37 Following the gen-
eral procedure, 1 (200 mg, 0.42 mmol) was demetalated to
afford, after chromatographic purification (7:1 n-hexanes-
EtOAc), the known 6 (38.1 mg, 73%) as a colorless oil. 1H NMR
(CDCl3, 400 MHz): δ 6.86 (dt, J ) 10.1, 4.1 Hz, 1H), 6.02 (dt,
J ) 10.1, 1.9 Hz, 1H), 2.27 (s, 2H), 2.24 (dd, J ) 4.1, 1.9 Hz,
2H), 1.04 (s, 6H).
(37) (a) Hiegel, G. A.; Burk, P. J . Org. Chem. 1973, 38, 3637-3639.
(b) Clark, R. D.; Heathcock, C. H. J . Org. Chem. 1973, 38, 3658. See
also: (c) Blankenship, R. M. Burdett, K. A.; Swenton, J . S. J . Org.
Chem. 1974, 39, 2300-2301. (d) J ulia, M.; Blasioli, C. Bull. Soc. Chim.
Fr. 1976, 1941-1946. (e) Baldwin, S. W.; Wilkinson, J . M. J . Am.
Chem. Soc. 1980, 102, 3634-3635. (f) Martinez, A. G.; Alvarez, R. A.;
Casado, M. M.; Subramanian, L. R.; Hanack, M. Tetrahedron 1987,
43, 275-279. (g) Frimer, A. A.; Gilinsky-Sharon, P.; Aljadeff, G.;
Gottlieb, H. E. Hameiri-Bunch, J .; Marks, V.; Philosof, R.; Rosental,
Z. J . Org. Chem. 1989, 54, 4853-4866. (h) Wang, W.; Pan, X.; Cui, Y.;
Chen, Y. Tetrahedron 1996, 52, 10659-10666. (i) Dauben, W. G.;
Shaffer, G. W.; Vietmeyer, N. D. J . Org. Chem. 1968, 33, 4060-4069.
(38) Chen, L. C.; Wang, E. C.; Lin, J . H.; Wu, S. S. Heterocycles 1984,
22, 2769.
(35) The protodemetalation is not simply due to the acidic nature
of PDC, since neither HCl nor TFA induced protodemetalation of
complex (()-16 under the same conditions.
(36) For general methods, see the Supporting Information.
5776 J . Org. Chem., Vol. 67, No. 16, 2002

Oxidative Demetalation Protocol for Mo π-Complexes
for C12H11NO3: C, 66.35; H, 5.10; N, 6.45. Found: C, 66.08;
H, 5.23; N, 6.54.
(()-(7R,8S,8a R)-7,8-Dim eth yl-8-for m yl-6,7,8,8a -tetr a h y-
d r o-2H-ch r om en -2- on e [(()-24].1d Following the general
procedure, (()-19 (65 mg, 0.12 mmol) was demetalated to
afford, after chromatographic purification (5:1 n-hexanes-
EtOAc), (()-24 (18 mg, 75%) as a white solid. TLC (3:1
n-hexanes-EtOAc): Rf ) 0.20. Mp: 112-113 °C. IR (cm-1):
2980 (w), 2918 (w), 2883 (w), 1718 (s), 1698 (s), 1648 (m), 1455
(w), 1401 (m), 1243 (m), 1023 (m). 1H NMR: δ 9.91 (s, 1H),
7.01 (d, J ) 9.5 Hz, 1H), 6.11 (m, 1H), 5.91 (d, J ) 9.5 Hz,
1H), 5.00 (m, 1H), 2.56 (bd, J ) 20.6 Hz, 1H), 2.27 (pent, J )
6.7 Hz, 1H), 2.05 (dd, J ) 20.6, 5.1 Hz, 1H), 1.31 (s, 3H), 1.00
(d, J ) 7.0 Hz, 3H). 13C NMR: δ 203.4, 164.2, 143.2, 135.0,
127.8, 117.6, 77.7, 50.5, 33.0, 31.4, 17.4, 15.9. HRMS [M+]:
calcd for C12H14O3, 206.0944; found, 206.0943.
(()-5-Hydr oxy-5-vin yl-5,6-dih ydr o-2H-pyr an -2-on e (14).
Following the general procedure, 12 (275 mg, 0.56 mmol) was
demetalated to afford, after chromatographic purification (2:1
n-hexanes-EtOAc), 14 (59.0 mg, 75%) as a colorless oil. TLC
(2:1 n-hexanes-EtOAc 2:1): Rf ) 0.12. IR (neat, cm-1): 3424
1
(s), 2930 (w), 1749 (s), 1208 (m). H NMR (CDCl3, 400 MHz):
δ 7.43 (d, J ) 5.7 Hz, 1H), 6.12 (d, J ) 5.7 Hz, 1H), 5.92 (dd,
J ) 17.4, 10.6 Hz, 1H), 5.43 (d, J ) 17.4 Hz, 1H), 5.33 (d, J )
10.6 Hz, 1H), 3.88 (d, J ) 12.1 Hz, 1H), 3.78 (d, J ) 12.1 Hz,
1H), 2.65 (bs, 1H). 13C NMR (CDCl3, 100 MHz): δ 172.5, 155.9,
131.9, 121.7, 118.4, 91.2, 65.3. HRMS [M - OH]+: calcd for
C7H7O2, 123.0446; found, 123.0447.
(()-(3a S,9a S,9bS)-2-Meth yl-1,2,3-tr ioxo-3a ,8,9a ,9b-tet-
r a h yd r o-2H,4H-p yr a n o[2,3-e]isoin d ole [(()-25]. Following
the general procedure, (()-20 (75 mg, 0.13 mmol) was demeta-
lated to afford, after chromatographic purification (9:1 CH2-
Cl2-EtOAc), (()-25 (25.0 mg, 83%) as a white solid. TLC (1:1
n-hexanes-EtOAc): Rf ) 0.06. Mp: >200 °C. IR (cm-1): 2957
(w), 2926 (w), 1938 (w), 1849 (w), 1725 (s), 1695 (s), 1436 (m),
(()-5-(Acet yloxy)-5-m et h yl-5,6-d ih yd r o-2H -p yr a n -2-
on e (15). Following the general procedure, 13 (400 mg, 0.77
mmol) was demetalated to afford, after chromatographic
purification (9:1 n-hexanes-EtOAc), 15 (98 mg, 75%) as a
colorless oil. TLC (8:1 n-hexanes-EtOAc 8:1): Rf ) 0.31. IR
(neat, cm-1): IR (neat, cm-1): 1733 (s), 1235 (s), 1131 (m), 1100
1
(m), 1061 (m), 1015 (w), 829 (w). H NMR (CDCl3, 400 MHz):
1
1386 (m), 1289 (m), 1231 (m), 1092 (m). H NMR: δ 6.91 (d,
δ 7.18 (dd, J ) 10 Hz, J ) 1.44 Hz, 1H), 5.99 (d, J ) 10 Hz,
1H), 4.51 (dd, J ) 12 Hz, J ) 1.44 Hz, 1H), 4.21 (d, J ) 12 Hz,
1H), 2.02 (s, 3H), 1.59 (s, 3H). 13C NMR (CDCl3, 100 MHz):
169.9, 162.2, 147.2, 120.7, 73.6, 72.1, 21.3, 20.3. HRMS
(FAB): Cald for C8H10O4Li [M+ + Li], 177.0739; found,
177.0741. Anal. Calcd for C8H10O4: C, 56.47; H, 5.92. Found:
C, 56.45; H, 5.60.
J ) 9.8 Hz, 1H), 6.10 (m, 1H), 5.93 (d, J ) 9.8 Hz, 1H), 5.26
(dt, J ) 6.0, 2.8 Hz,1H), 3.65 (dd, J ) 8.9, 6.7 Hz, 1H), 3.24
(bt, J ) 8.9 Hz, 1H), 2.97 (ddd, J ) 16.5, 7.0, 1.3 Hz, 1H), 2.92
(s, 3H), 2.10-2.02 (m, 1H). 13C NMR: δ 178.1, 174.3, 161.2,
139.5, 131.1, 127.9, 118.1, 74.3, 44.1, 36.9, 25.2, 25.0.
(()-3,6-Dih yd r o-2H-p yr a n -2-on e [(()-29].31a-h Following
the general procedure, (()-4 (370 mg, 0.79 mmol) was demeta-
lated to afford, after chromatographic purification (4:1 n-hex-
anes-EtOAc), the known (()-29 (39 mg, 50%) as a colorless
oil. 1H NMR (300 MHz): δ 3.12 (m, 2H), 4.93 (m, 2H), 5.92
(m, 2H).
(+)-(8S,8a S)-8-(Meth oxyca r bon yl)-6,7,8,8a -tetr a h yd r o-
2H-ch r om en -2-on e [(+)-21].1d Following the general proce-
dure, a 98% ee sample of (-)-16 (136 mg, 0.24 mmol) was
demetalated to afford, after chromatographic purification (CH2-
Cl2), (+)-21 (43.0 mg, 85%) in 98% ee {[R]D +438.5 (c 0.6, CH2-
Cl2)} as a white solid. TLC (4:1 n-hexanes-EtOAc 4:1) Rf )
0.07. Mp: 117-118 °C. IR (cm-1): 2953 (w), 1714 (s), 1644
(m), 1436 (w), 1239 (w), 1197 (m), 1166 (m), 1119 (w), 1054
(-)-(6S)-6-((Acetyloxy)m eth yl)-3,6-d ih yd r o-2H-p yr a n -
2-on e [(-)-30].39 Following the general procedure, (+)-26 (360
mg, 0.66 mmol) was demetalated to afford, after chromato-
graphic purification (5:1 n-hexanes-EtOAc), (-)-30 (79 mg,
71%) as a colorless oil: [R]D -112 (c 2.1, CHCl3) {lit. [R]D
-113.2 (c 1.25, CHCl3)}.31i TLC (4:1 n-hexanes-EtOAc): Rf )
0.30. IR (cm-1): 1741 (s) 1378 (m), 1220 (s), 1166 (w), 1104
1
(m). H NMR: δ 6.98 (d, J ) 9.8 Hz, 1H), 6.09 (m, 1H), 5.85
(d, J ) 9.8 Hz, 1H), 5.21 (m, 1H), 3.70 (s, 3H), 3.30 (q, J ) 5.4
Hz, 1H), 2.47-2.36 (m, 1H), 2.32-2.82 (m, 1H), 2.20-2.13 (m,
1H), 2.03-1.95 (m, 1H). 13C NMR: δ 171.1, 163.6, 143.4, 133.9,
128.5, 117.2, 74.3, 51.8, 41.8, 23.2, 23.0. HRMS [M+]: calcd
for C11H12O4, 208.0736; found, 208.0742.
1
(m), 1046 (m), 714 (w). H NMR (300 MHz): δ 5.99-5.91 (m,
1H), 5.86-5.75 (m, 1H), 5.15 (bs, 1H), 4.35-4.17 (m, 1H), 3.08
(bs, 1H), 2.08 (s, 3H). 13C NMR: δ 170.4, 167.9, 123.9, 122.1,
77.3, 64.9, 29.7, 20.6. HRMS (FAB): cald for C8H10O4Li [M++
Li], 177.0739; found, 177.0740. Anal. Calcd for C8H10O4: C,
56.47; H, 5.92. Found: C, 56.40; H, 5.74.
(+)-(8S,8a S)-8-Acetyl-6,7,8,8a -tetr a h yd r o-2H-ch r om en -
2-on e [(+)-22].1d Following the general procedure, a 98% ee
sample of (-)-17 (57 mg, 0.10 mmol) was demetalated to afford,
after chromatographic purification (22:1 CH2Cl2-EtOAc), (+)-
22 (16.1 mg, 80%) in 98% ee {[R]D +285 (c 1, CH2Cl2)} as a
white solid. TLC (1:1 n-hexanes-EtOAc 1:1): Rf ) 0.21. Mp:
104-105 °C. IR (cm-1): 2930 (w), 1710 (s), 1644 (m), 1355 (w),
1239 (m), 1162 (m), 1504 (m). 1H NMR: δ 6.98 (d, J ) 10.1
Hz, 1H), 6.08 (m, 1H), 5.84 (d, J ) 10.1 Hz, 1H), 5.25 (m, 1H),
3.33 (q, J ) 4.4 Hz, 1H), 2.46-2.34 (m, 1H), 2.28-2.19 (m,
1H), 2.25 (s, 3H), 2.14-2.07 (m, 1H), 1.99-1.90 (m, 1H). 13C
NMR: δ 206.7, 163.8, 143.5, 134.3, 128.5, 117.1, 74.7, 47.9,
30.8, 23.3, 22.3. HRMS [M+]: calcd for C11H12O3, 192.0786;
found, 192.0790.
(-)-(6S)-6-(H yd r oxym et h yl)-3,6-d ih yd r o-2H -p yr a n -2-
on e [(-)-31]. Following the general procedure, (+)-28 (475 mg,
0.95 mmol) was demetalated to afford, after chromatographic
purification (2:1 n-hexanes-EtOAc), (-)-31 (99 mg, 82%) as a
colorless oil: [R]D -48 (c 0.8, CHCl3). TLC (2:1 n-hexanes-
EtOAc): Rf ) 0.16. IR (cm-1): 3424 (br), 2922 (br), 2856 (w),
2362 (br), 1729 (s), 1459 (w), 1417 (w), 1382 (w), 1247 (m),
1
1166 (m), 1054 (m), 934 (w). H NMR: δ 6.06-5.78 (m, 2H),
5.05 (m, 1H), 3.85 (dd, J ) 13.7, 4.0 Hz, 1 H), 3.65 (dd, J )
13.7, 7.1 Hz, 1 H), 3.11-2.89 (m, 2H), 3.84 (bs, 1H). 13C NMR:
δ 171.6, 81.1, 64.7, 29.5, 23.5, 18.2. HRMS (FAB): cald for
C8H10O4Li [M+ + Li], 135.0687; found, 135.0633. Anal. Calcd
for C6H8O3: C, 56.25; H, 6.29; N, 37.46. Found: C, 56.47; H,
6.49; N, 37.24.
(+)-(8R,8a S)-8-Bu tyl-8-for m yl-6,7,8,8a -tetr a h yd r o-2H-
ch r om en -2-on e [(+)-23].1d Following the general procedure,
a 99.8% ee sample of (-)-18 (77 mg, 0.13 mmol) was demeta-
lated to afford, after chromatographic purification (6:1 n-hex-
anes-EtOAc), (+)-23 (22.2 mg, 72%) in 99.8% ee {[R]D +256.5
(c 0.5, CH2Cl2)} as a white solid. TLC (6:1 n-hexanes-EtOAc
6:1): Rf ) 0.11. Mp: 78-80 °C. IR (cm-1): 2961 (m), 2934 (m),
(+)-(6S)-6-(Hyd r oxym eth yl)-3,4,5,6-tetr a h yd r o-2H-p y-
r a n -2-on e [(+)-32].39 To a solution of (-)-31 (160 mg, 1.25
mmol) in 1.5 mL of ethyl acetate was added 10 wt % Pd/C (50
mg, 0.11 mmol), and the mixture was stirred at room temper-
ature under H2 (1 atm) for 12 h. The reaction mixture was
passed through a pad of Celite, and the filtrate was concen-
trated to give pure (+)-32 (14 mg, 85%) as a colorless oil: [R]D
+35.2 (c 1.3, CHCl3) {lit. [R]D +34.68 (c 1.25, CHCl3)}.31i TLC
(2:1 n-hexanes-EtOAc): Rf ) 0.37. 1H NMR (300 MHz): δ
1
2868 (w), 1718 (s), 1644 (m), 1401 (w), 1235 (m), 1046 (m). H
NMR: δ 9.88 (d, J ) 1.6 Hz, 1H), 6.97 (d, J ) 9.5 Hz, 1H),
6.10 (bs, 1H), 5.88 (d, J ) 9.5 Hz, 1H), 5.11 (m, 1H), 2.47-
2.35 (m, 1H), 2.32-2.22 (m, 1H), 2.19 (dd, J ) 14.0, 6.3 Hz,
1H), 1.95-1.88 (m, 1H), 1.73-1.65 (m, 1H), 1.54-1.45 (m, 1H),
1.38-1.27 (m, 3H), 1.22-1.13 (m, 1H), 0.91 (t, J ) 7.3 Hz, 3H).
13C NMR: δ 203.0, 163.9, 143.4, 136.5, 128.5, 116.9, 78.2, 51.0,
32.2, 25.4, 25.1, 23.5, 23.1, 13.9.
(39) Although compounds (-)-30 and (+)-32 are known (see ref 31i),
their analytical and spectroscopic data have not been reported.
J . Org. Chem, Vol. 67, No. 16, 2002 5777

Alcudia et al.
4.45-4.38 (m, 1H), 3.78 (dd, J ) 12.1, 3.2 Hz, 1H), 3.66 (dd,
J ) 12.1, 5.5 Hz, 1H), 2.66-2.57 (m, 1H), 2.49-2.41 (m, 1H),
1.97-1.82 (m, 1H), 1.73-1.68 (m, 1H). 13C NMR: δ 171.5, 81.1,
64.8, 29.5, 23.5, 18.2.
Llorente, and J ingjun Yin for their earlier preparation
of samples of molybdenum complexes (+)-27, 10, and
13, respectively.
Su p p or tin g In for m a tion Ava ila ble: A complete descrip-
tion of the synthesis and analytical and spectral characteriza-
tion data of all molybdenum complexes used in this study and
copies of proton and carbon NMR spectra of all new com-
pounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
Ack n ow led gm en t. This work was supported by
Grant No. GM43107, awarded by the National Institute
of General Medical Sciences, DHHS. A.A. and R.G.A.
thank the Secretar´ıa de Estado de Educacio´n y Univer-
sidades (Spain) and NATO, respectively, for postdoctoral
fellowships. We also thank Drs. Almudena Rubio, Isidro
J O020002X
5778 J . Org. Chem., Vol. 67, No. 16, 2002