C O M M U N I C A T I O N S
Table 3. Exploration of Scope for Suzuki Reaction in Upper Ring
Scheme 1. Further Functionalization of Tetra-ortho-Substituted
Biaryl 16b
In conclusion, a DAB strategy has been developed for the
construction of highly functionalized biaryl templates utilizing
arylacetylenic stannanes and cyclic dienes. The sequential func-
tionalization of a representative template compound 11c has been
demonstrated. Highly active boroxine-based, anhydrous Suzuki
coupling conditions have been developed which should be of
considerable interest to the synthetic community. Finally, the ability
to resolve an axially chiral anilino phenol has been demonstrated.
Further application of this DAB strategy will be reported in due
course.
as 13a through our own unsuccessful previous experience with tetra-
ortho-substituted aryl chlorides in our phosphorus-containing
biaryls.2b As a methyl moiety is the least sterically demanding of
the carbon-based nucleophiles, we used commercially available
methyl boroxine as the coupling partner for the initial investigation.
We screened a wide range of coupling systems including those
developed by Fu [(t-Bu3P)2Pd]5 and Buchwald [Pd(OAc)2, S-Phos].6
We were disappointed to observe only poor or no reaction in all
cases. We next turned our attention to the recently developed and
commercially available PEPPSI-IPr catalyst (15) by Organ and co-
workers.7 We were quite pleased to observe clean conversion to
the Suzuki product 16a in good yield (74%). When we explored
alternate boron-based nucleophiles such as PhB(OH)2, we were
surprised to observe no reactionseven at high catalyst loading and
with excess boronic acid. As our boron source for the successful
coupling to produce 16a had employed the boroxine 14, we felt it
would be prudent to screen the analogous phenyl boroxine 14b8 in
the reaction protocol. We were quite gratified to find clean
construction of the tetra-ortho-substituted biaryl 16b. Optimum
conditions employed 3 equiv of the boroxine 14 and powdered 4
Å molecular sieves in order to remove any adventitious water. To
the best of our knowledge, the unique and powerful role of the
boroxines in Suzuki couplings has not been previously reported.9
These conditions have proven to be the most reactive that we have
found during our studies in challenging C-C bond forming
reactions.2 Additionally, reasonable functional group tolerance was
observed using this reaction protocol. Electron donating substituents
in the ortho, meta, and para positions of the aryl boroxine are all
tolerated. One limitation appears to be the 2,6-dimethylphenyl
boroxine 14f. Successful coupling with electron deficient boroxine
14g was also observed in reasonable yield (50%).
Orthogonal and/or tandem functionalization of these highly
substituted biaryls could be readily accomplished (Scheme 1).
Selective formation of the ortho-anilino or ortho-phenolic func-
tionalities were demonstrated using Zn/HOAc or BCl3, respectively.
Tandem reduction using Pd/C, H2 revealed the anilino phenol rac-
19 in excellent yield. This biaryl could be readily resolved using
chiral HPLC separation (Daicel OD column). These axially chiral
anilino phenols 19-(aR) and 19-(aS)10 should be of considerable
interest to the synthetic community as they closely resemble the
2-amino-2′-hydroxy-1,l′-binaphthyl (NOBIN) class of binapthalene-
based ligands. Interestingly, while NOBIN has been utilized in
asymmetric catalysissincluding in Carreira’s asymmetric aldol
methodology,11 little variation of the binapthalene core structure
has been explored to date.
Acknowledgment. Financial support was provided by the
National Science Foundation (CHE-0549884). The authors would
like to thank Professor Max Deinzer (OSU) and Dr. Jeff Morre´
(OSU) for mass spectra data and Bradley O. Ashburn (OSU) and
Dr. Roger Hanselmann (Rib-X Pharmaceuticals) for their helpful
discussions.
Supporting Information Available: Complete experimental pro-
1
cedures, including H and 13C spectra, of all new compounds. This
References
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