Stereoselective umpolung tandem addition of heteroatoms to phenol

Article abstract of DOI:10.1021/ja801076z

Upon coordination to {TpW(PMe₃)(NO)}, phenol tautomerizes to a cyclohexadienone (a 2H-phenol). The uncoordinated, nonaromatic double bond of this ligand undergoes stepwise addition of electrophiles followed by nucleophiles to produce 4,5-disubstituted cyclohexenone complexes. The metal stabilizes the intermediate cationic ligand and sterically blocks one face of the ligand, resulting in a high degree of stereo- and regiocontrol. These substituted cyclohexenones are readily liberated from the metal by oxidative decomplexation. Copyright

Full text of DOI:10.1021/ja801076z

Published on Web 05/13/2008
Stereoselective Umpolung Tandem Addition of Heteroatoms to Phenol
†
†
‡
‡
,†
Michael A. Todd, Michal Sabat, William H. Myers, Timothy M. Smith, and W. Dean Harman*
Department of Chemistry, UniVersity of Virginia, CharlottesVille, Virginia 22904, and Department of Chemistry,
UniVersity of Richmond, Richmond, Virginia 23173
Received February 12, 2008; E-mail: wdh5z@virginia.edu
Although phenol normally exists in solution as an enol, when
coordinated to a transition metal, its dienone tautomers can become
Scheme 1. Stepwise Addition of An Electrophile and A Nucleophile
2
to TpW(NO)(PMe3)(η -2H-phenol); [W] ) {TpW(NO)(PMe3)}
energetically competitive. For example, the dihapto-coordinated
2
phenol complex, TpW(NO)(PMe
3
)(5,6-η -phenol), 1, can be iso-
1
,2
lated as a single diastereomer of the 2H-phenol tautomer. This
nonaromatic form of phenol was recently reported to undergo
2
regioselective [2 + 2] cycloaddition reactions with ketenes.
Interestingly, the electrophilic carbon of the ketene was found to
selectively add to C3, suggesting that the meta carbon of the phenol
ring was nucleophilic. This observation was an umpolung of the
reactivity pattern normally associated with phenol, in which
3
electrophiles add to C2, C4, or oxygen. We speculated that this
[
2 + 2] cyclization occurs sequentially, passing through an allyl
cation intermediate that is stabilized by the electron-rich tungsten
2
atom (Scheme 1). The aim of the present study was to determine
Scheme 2. The Synthesis of Complexes 2-7; [W] )
TpW(NO)(PMe3)
if this reaction pattern could be generalized for independent
combinations of electrophiles and nucleophiles.
Previously reported tandem addition sequences with dihapto-
coordinated arene complexes were initiated by the addition of a
4–7
proton or carbon-based electrophile. Heteroatomic electrophiles
are generally strong oxidants and were found to be incompatible
with this electron-rich W(0) system. However, the dienone ligand
of complex 1 is an excellent π-acid which has the effect of
considerably raising the reduction potential of the metal (Ep,a
)
1
+
0.80 V, cf -0.18 V for the anisole analogue (NHE)). We
reasoned that this property would improve the chances that a ligand-
centered reaction could pre-empt a reaction occurring at the metal
(
e.g., oxidation).
Our initial aim was to oxygenate C3 of the bound phenol of 1,
either directly (see Scheme 1, path B) or through an epoxide
intermediate (path A) that could be opened with a suitable
8
nucleophile. Gratifyingly, when meta-chloroperbenzoic acid (mCP-
2
BA) was added to TpW(NO)(PMe
3
)(η -2H-phenol) in CH
2
Cl
2
, at
0
°C, followed by methanol, the addition proceeded smoothly to
form the alkoxyhydroxyenone 2, as a single diastereomer, in 82%
yield (Scheme 2). Of note, mCPBA has previously been used in
our laboratories (unpublished observations) to oxidatively decom-
(H4) with 3.0 Hz coupling constants, analogous to that observed
for 2, implying that the tandem addition has similar stereochemistry.
A sequential addition of mCPBA and morpholine yielded the
aminohydroxyenone 4 in 69% yield. The H4-H3 coupling constant
of 4 (4.5 Hz) is slightly larger than that for 2 and 3, but single-
crystal X-ray diffraction analysis (Figure 1) reaffirms the cis-tandem
addition away from the metal.
3
plex alkene and arene complexes of {TpW(NO)(PMe )}, but in
this case, no metal oxidation was apparent. An analysis of NMR
and X-ray crystallographic data (Figure 1) indicates that both
electrophilic (OH) and nucleophilic (OMe) additions occur anti to
the metal fragment. Key spectral features include J3,4 and J4,5
We endeavored to expand the scope of this reaction to other
heteroatomic electrophiles. Recently, Kirschning et al. developed
a method for the functionalization of olefins by oxidizing halide
3
4
4 5
coupling constants of 3.0 Hz, indicating HC C H and HC C H
dihedral angles in the range of 60-90°. The X-ray structure also
confirms the regiochemistry of the addition.
9
,10
anions with diacetoxyiodobenzene (DIB).
when a solution of DIB and Ph PMeBr (MTPBr) in acetic acid is
True to expectation,
In order to test the generality of this reaction with other
nucleophiles, mCPBA was added, followed by thiophenol, to give
complex 3 in 83% yield. NMR data show a triplet at 4.56 ppm
3
added to 1, bromoacetoxylation results in analogue 5 in 61% yield.
This complex is water-sensitive both in solution and in the solid
state and decomposes to form a paramagnetic material within
approximately 1-2 days. While this reaction may be performed in
air, the complex should be stored under an inert atmosphere.
†
University of Virginia.
University of Richmond.
‡
6
906 9 J. AM. CHEM. SOC. 2008, 130, 6906–6907
10.1021/ja801076z CCC: $40.75  2008 American Chemical Society

C O M M U N I C A T I O N S
polarization of C3 and C4. Thus, oxygen, bromine, and fluorine
electrophiles may be combined with oxygen, sulfur, and nitrogen
nucleophiles to regio- and stereoselectively convert phenol into cis-
4,5-disubstitued cyclohex-2-en-1-ones. The versatility of this reac-
tion sequence and its stereofidelity coupled with the ease in handling
Figure 1. Ortep diagram of complexes 2 and 4.
Attempts to generalize the DIB-mediated addition of the bro-
minium ion using other nucleophiles failed, yielding either no
reaction or mixtures of complexes containing 5. To circumvent this
problem an alternate oxidant, phenyliodobis(trifluoroacetate) (PIFA),
was used. The trifluoroacetate groups in PIFA are less nucleophilic
than the acetate groups in DIB and do not react with the presumed
allyl cation intermediate. A solution of PIFA and MTPBr in
methylene chloride was added to 1 at -40 °C, followed by methanol
to generate the bromo-methoxy analogue 6 in 74% yield. This
reaction must be run at low temperature because the intermediate
complex is unstable under ambient conditions. As with 5, this
complex is water-sensitive.
11
of synthon 1 make this a potentially valuable new method for
the preparation of functionalized cyclohexenones.
Acknowledgment. This work was supported by the NSF (CHE-
0111558 (UVA), 9974875 (UVA), 0116492 (UR), and 0320669
(UR)).
Supporting Information Available: Full synthetic details for the
preparation of compounds 2-8, selected spectra of these compounds,
and crystallographic information for 2 and 4. This material is available
free of charge via the Internet at http://pubs.acs.org.
References
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-
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(
(
(
(
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metal by oxidative decomplexation. For example, the ligand
5
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(
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(
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(
11) In contrast to our earlier reports of analogous metal-arene complexes, the
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of these materials resulted in significant elimination of HX and
rearomatization to 4-acetoxy- and 4-methoxyphenol, respectively.
An electron-rich tungsten complex {TpW(NO)(PMe
3
)} has been
shown to trap phenol as its 2H-phenol tautomer and reverse the
JA801076Z
J. AM. CHEM. SOC. 9 VOL. 130, NO. 22, 2008 6907