Formation of o-quinone methides from η2-coordinated phenols and their controlled release from a transition metal to generate chromans

Article abstract of DOI:10.1021/om0305317

Phenol or p-cresol is bound to osmium(II) and combined with an aldehyde to generate remarkably stable η²-coordinated o-quinone methide complexes. When these materials are treated with an oxidant (CAN, Cu(II)), the o-quinone methide is liberated and can be trapped with suitable alkenes to generate chromans.

Full text of DOI:10.1021/om0305317

4170
Organometallics 2003, 22, 4170-4171
F or m a tion of o-Qu in on e Meth id es fr om η2-Coor d in a ted
P h en ols a n d Th eir Con tr olled Relea se fr om a Tr a n sition
Meta l To Gen er a te Ch r om a n s
Sterling M. Stokes, J r., Fei Ding, Philip L. Smith, J oseph M. Keane,
Michael E. Kopach, Ramiro J ervis, Michal Sabat, and W. Dean Harman*
Department of Chemistry, University of Virginia, Charlottesville, Virginia 22904-4319
Received J uly 9, 2003
Sch em e 1. Meta l-P r om oted F or m a tion of o-QM
Summary: Phenol or p-cresol is bound to osmium(II) and
combined with an aldehyde to generate remarkably
stable η2-coordinated o-quinone methide complexes. When
these materials are treated with an oxidant (CAN,
Cu(II)), the o-quinone methide is liberated and can be
trapped with suitable alkenes to generate chromans.
a n d Its Con tr olled Relea se
While quinone methides (QMs) are usually far too
reactive to be isolated,1 they represent an important
class of intermediates in synthetic chemistry and in
biochemistry.2 In particular, o-QMs are valuable as
precursors to chromans, serving as heterodienes for both
inter- and intramolecular Diels-Alder reactions.3 One
of the most common methods for their generation is from
the dehydration of o-hydroxybenzyl alcohols, by pyroly-
sis,4 photolysis,5 or catalysis by Lewis acids.6 Recently,
two independent research groups have reported ex-
amples of QMs stabilized by coordination to a transition
metal.7,8 If a hydroxybenzyl alcohol bound to a transition
metal were to undergo dehydration, the resulting o-QM
could be stabilized and subsequently released in the
presence of a dienophile to form the chroman ring
system.
Our longstanding interest in transition-metal-based
dearomatization agents9 led us to investigate the reac-
tivity of η2-phenol complexes with various carbon elec-
trophiles.10 Herein we wish to report that phenols, when
bound to pentaammineosmium(II), readily react with
aldehydes to generate complexes of o-quinone methides.
While these complexes are remarkably stable, when
exposed to air or dissolved in water, treatment with
CAN oxidizes the metal and releases the intact QM
ligand, which can be trapped by a suitable dienophile
(Scheme 1).
pound [Os(NH3)5(η2-phenol)](OTf)2 (1).10 When 1 was
treated with crotonaldehyde under neutral conditions,
three osmium complexes were isolated. Although two
of these were Michael adducts, the third was the product
of an aldol condensation followed by dehydration to form
the o-QM complex 2.
Repeating this reaction with acetaldehyde in place of
crotonaldehyde resulted in the formation of the o-QM
3 along with small amounts of the η2-acetaldehyde
Our first experience with this reaction was during an
investigation of the Michael reactions with the com-
complex [Os(NH3)5(acetaldehyde)]2+ 11
The addition of
.
a small amount of pyridine accelerated the aldol con-
densation, thus preempting ligand substitution. DEPT
* To whom correspondence should be addressed. E-mail: wdh5z@
virginia.edu.
(1) McIntosh, C. L.; Chapman, O. L. J . Chem. Soc., Chem. Commun.
1971, 771.
(2) Tomasz, M.; Chawla, A. K.; Lipman, R. Biochemistry 1988, 27,
3182.
(3) Boger, D. L.; Weinreb, S. N. Hetero Diels-Alder Methodology in
Organic Synthesis; Academic Press: New York, 1987.
(4) Yato, M.; Ohwada, T.; Shudo, K. J . Am. Chem. Soc. 1990, 112,
5341.
(5) Diao, L.; Yang, C.; Wan, P. J . Am. Chem. Soc. 1995, 117, 5369.
(6) Chiba, K.; Hirano, T.; Y., K.; Tada, M. Chem. Commun. 1999,
691.
(7) Milstein, D.; Vigalok, A. Acc. Chem. Res. 2001, 34, 798.
(8) Amouri, H.; Le Bras, J . Acc. Chem. Res. 2002, 35, 501.
(9) Harman, W. D. Chem. Rev. 1997, 97, 1953-1978.
(10) Kopach, M. E.; Harman, W. D. J . Am. Chem. Soc. 1994, 116,
6581.
1
and H NMR data for 3 indicate three downfield (6.5-
7.1 ppm) and two upfield (4.7-5.2 ppm) methine reso-
nances along with a methyl and two ammine signals,
while 13C NMR data include resonances corresponding
to a carbonyl (199.8 ppm) and three uncoordinated
methine carbons (133, 131, and 118 ppm). Homonuclear
decoupling experiments and NOE data support the
formation of the E diastereomer, as shown in Chart 1.
While the NMR spectra indicated only one species
present in a sample of 3, cyclic voltammetry disclosed
(11) Harman, W. D.; Sekine, M.; Taube, H. J . Am. Chem. Soc. 1988,
110, 2439-2445.
10.1021/om0305317 CCC: $25.00 © 2003 American Chemical Society
Publication on Web 09/16/2003

Communications
Organometallics, Vol. 22, No. 21, 2003 4171
Ch a r t 1
An example of an intramolecular Diels-Alder reac-
tion was achieved using the o-QM 12, formed by treating
the phenol complex 1 with (R)-citronellal and pyridine.
Treatment of 12 with CAN effected demetalation and
cycloaddition to form the benzo[c]chromene 13 in 52%
yield. Proton NMR data indicate that 13 is formed as a
single diastereomer, as was originally reported by
Talley.13 1H NMR data exactly match those reported for
the isomer shown above.
the presence of a significant byproduct (30-40%) char-
acterized by a cathodic wave near -1.0 V vs NHE.
Attempts to purify 3 by recrystallization resulted in-
stead in isolation of the impurity, determined by X-ray
diffraction (Supporting Information) to be the phenoxide
complex [OsIII(NH3)5(OPh)]2+. Attempts to remove this
impurity from 3 (as the triflate salt) by recrystallization
or chromatography were unsuccessful.
Although the reactions reported herein do not occur
with optimal efficiency, they represent a novel approach
to the manipulation of QMs in which a transition metal
promotes the formation and protects the QM for later
use. Related to our findings, Milstein et al. have
reported a palladium complex of an η2-bound p-QM
(derived from BHT) that sheds the free p-QM upon
exposure to an electron-deficient alkene.7 Given the
exceptionally mild reaction conditions required for the
π-base-promoted aldol condensation of a phenol and
aldehyde and the ability to release the QM using a one-
electron oxidant, η2-coordinated QM complexes may
prove to be useful tools for synthetic chemistry and
biochemistry.
The phenol complex 1 also reacted with isobutyralde-
hyde, benzaldehyde, p-anisaldehyde, 4-(trifluoromethyl)-
benzaldehyde, 3-furaldehyde, and 2-furaldehyde to form
o-quinone methide complexes 4-9 (Chart 1). An o-QM
complex derived from crotonaldehyde (10) was prepared
by substituting the p-cresol complex for 1 in order to
block the competing Michael reaction (vide supra). In
1
all cases, H and 13C NMR data indicate formation of
only one diamagnetic species, but electrochemical data
indicate that the isolated materials contain ∼40% Os-
(III). These o-QM complexes can be purified by a
laborious procedure involving ion exchange chromatog-
Ack n ow led gm en t is made to the donors of the
Petroleum Research Fund, administered by the Ameri-
can Chemical Society, for partial support of this re-
search. This work was also supported by the NSF
(Grant Nos. CHE0111558 and 9974875) and the NIH
(NIGMS: Grant No. R01-GM49236).
-
raphy followed by precipitation from water as the BPh4
salts,11 but for ease we elected to use these materials
without purification.
The o-QM complex 3 was found to be completely
unreactive with electron-rich (e.g., dihydropyran) or
electron-deficient dienes (e.g., N-methylmaleimide). How-
ever, when an acetonitrile solution of 3 was combined
with an excess of 3,4-dihydropyran and 1.5 equiv of
CAN, the tetrahydropyranochromene 11 was recovered
in 41% yield (based on available o-QM), as a 3:1 ratio
of diastereomers. Although 11 has not previously been
Su p p or tin g In for m a tion Ava ila ble: Text giving experi-
mental preparations for 3-13 and an ORTEP diagram for [Os-
(NH3)5(OPh)](OTf)2. This material is available free of charge
via the Internet at http://pubs.acs.org.
OM0305317
(12) Amantini, D.; Fringuelli, F.; Pizzo, F. J . Org. Chem. 2002, 67,
7238.
(13) Talley, J . J . J . Org. Chem. 1985, 50, 1695.
1
prepared, 13C and H NMR data closely correspond to
those of the nitromethyl analogue.12