Journal of the American Chemical Society
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dearomatized intermediates generated from para-lithiated benzyl-
We thank the ERC (670668) and the EPSRC (EP/I038071/1) for
1
2
3
4
amines did not undergo a double 1,3-borotropic shift sequence
(Scheme 6c). Instead, a non-stereoselective von Auwers-type
reaction16 afforded arylboronic ester 3uo’ with formal inverse
1,4’-benzylidene insertion.
financial support. S.A. thanks the Austrian Science Fund (FWF)
for an Erwin Schrödinger fellowship (J3919-N28). R.B. thanks
the Swiss National Science Foundation fellowship program
(P2EZP2_165268).
The synthetic utility of the dearomatized intermediate is not re-
stricted to the 1,3-borotropic-shift process (Scheme 7). For exam-
ple, allylboration of benzaldehyde or ethyl glyoxalate afforded the
corresponding alcohols 5 and 6 with excellent diastereo- and
enantiocontrol (dr > 20:1, er = 95:5 and 91:9, respectively).17
Similarly to benzylic boronic esters (Scheme 6a), the intermediate
prepared from allylBpin underwent an enantiospecific Cope rear-
rangement to give 7 with 97:3 er. That the Cope rearrangement is
significantly more facile than the 1,3 borotropic shift was con-
firmed through computation (see SI for details). Finally, treatment
of the intermediate with TBAF trihydrate18 selectively yielded
protodeboronation product 8, an example in which the benzylic
amine acted as a traceless directing group.
5
6
7
8
REFERENCES
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9
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15
16
17
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28
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52
53
54
55
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57
58
59
60
Scheme 7. Synthetic Utility of Intermediate
In conclusion, a new strategy for the stereospecific synthesis of
ortho-substituted benzylic boronic esters has been developed. The
method relies on a 1,2-metalate rearrangement/anti-SN2’ reaction
followed by a suprafacial 1,3-borotropic shift giving rise to sp2–
sp3 cross-coupled products in high enantiopurity in which the
boronic ester moiety is retained for further transformations.
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ASSOCIATED CONTENT
Supporting Information.
The Supporting Information is available free of charge on the
ACS Publications website.
Detailed experimental procedures and characterization of all
products (PDF).
(14) (a) Kitazawa, Y.; Takita, R.; Yoshida, K.; Muranaka, A.; Matsub-
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S.; Kobayashi, H.; Mori, A.; Nagira, A.; Nie, J.; Sonoda, T.; Yagupolskii,
Y. Chem. Lett. 2000, 29, 62.
AUTHOR INFORMATION
Corresponding Author
(15) Due to 1H NMR signal overlap, determination of the dr of the
crude product was complicated, therefore the dr of isolated product after
flash chromatography is reported.
*v.aggarwal@bristol.ac.uk
Author Contributions
(16) Dumeunier, R.; Jaeckh, S. Chimia 2014, 68, 522.
(17) Ramachandran, P. V.; Gagare, P. D.; Nicponski, D. R. Al-
lylborons. In Comprehensive Organic Synthesis, 2nd ed.; Knochel, P.;
Molander, G. A., Eds.; Elsevier: Oxford, 2014; Vol. 2; p 1.
(18) Hesse, M. J.; Butts, C. P.; Willis, C. L.; Aggarwal, V. K. Angew.
Chem., Int. Ed. 2012, 51, 12444.
‡These authors contributed equally.
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
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