Journal of the American Chemical Society
Communication
complex, with, e.g., both Me and bulky groups considered to be
nonmigrating in specific cases. The final outcome is a delicate
balance between the intrinsic reactivity of the migrating group
Pure Appl. Chem. 2006, 78, 215. (and references therein). (b) Elliott, M.
C.; Smith, K. Organometallics 2013, 32, 4878.
(8) Indeed we had previously found that secondary alkyl groups
25
migrated in preference to Me groups, see Elford, T. G.; Nave, S.;
Sonawane, R. P.; Aggarwal, V. K. J. Am. Chem. Soc. 2011, 133, 16798.
and conformational effects.
In conclusion, lithiation-borylation methodology has been
used to construct adjacent multiple quaternary substituted
stereocenters with full control over relative and absolute
stereochemistry. The key to success has been the use of mixed
boranes which are more electrophilic and have a lower barrier to
(9) (a) Cabiddu, S.; Maccioni, A.; Secci, M. Gazz. Chim. Ital. 1972, 102,
5
55. (b) Shchegoleva, T. L.; Shashkova, E. M.; Mikhailov, B. M. Bull.
Acad. Sci. USSR Div. Chem. Sci. 1981, 858. (c) Hupe, E.; Marek, I.;
Knochel, P. Org. Lett. 2002, 4, 2861. (d) Fernandez, E.; Maeda, K.;
Hooper, M. W.; Brown, J. M. Chem.Eur. J. 2000, 6, 1840.
(10) The solutions can be stored indefinitely and the exact
concentration can be determined by 1H NMR, see Hoye, T. R.;
Eklov, B. M.; Voloshin, M. Org. Lett. 2004, 6, 2567.
1
,2-migration than boronic esters. In addition, an expedient
amination of tertiary boranes was developed, giving highly
hindered C-tertiary amines with excellent diastereo- and
enantioselectivity.
(
11) Without modification of conditions, 5−10% of ent-5a was also
formed. We believe this originates from the presence of a small amount
of unreacted iPrMe B which remained after the first homologation and
then reacted twice with excess ent-Li-1. This was solved by evaporation
of all the volatiles after the first homologation which removed the excess
2
ASSOCIATED CONTENT
Supporting Information
Experimental procedures, spectroscopic data for all products, and
■
*
S
iPrMe
12) Pulis, A. P.; Blair, D. J.; Torres, E.; Aggarwal, V. K. J. Am. Chem.
Soc. 2013, 135, 16054.
13) The homologation of EtBMe with carbamate 1a gave a 2:3 ratio
B and thus led to high diastereoselectivity.
2
(
(
2
of methyl and ethyl migrated products.
AUTHOR INFORMATION
(14) It is possible that racemization occurred by a boron-magnesium
metathesis reaction. See Reichle, M. A.; Breit, B. Angew. Chem., Int. Ed.
2012, 51, 5730.
(15) Nave, S.; Sonawane, R. P.; Elford, T. G.; Aggarwal, V. K. J. Am.
Chem. Soc. 2010, 132, 17096.
Author Contributions
C.G.W. and A.B. contributed equally.
(16) Burns, M.; Essafi, S.; Bame, J. R.; Bull, S. P.; Webster, M. P.;
Balieu, S.; Dale, J. W.; Butts, C. P.; Harvey, J. N.; Aggarwal, V. K. Nature
2014, 513, 183.
Notes
(
17) In Zweifel olefination of boranes, it is known that the smallest
group usually migrates. See (a) Slayden, S. W. J. Org. Chem. 1981, 46,
311. (b) Slayden, S. W. J. Org. Chem. 1982, 47, 2753. (c) Brown, H. C.;
The authors declare no competing financial interest.
2
ACKNOWLEDGMENTS
■
Basavaiah, D.; Kulkarni, S. K.; Lee, H. D.; Negishi, E.; Katz, J. J. J. Org.
Chem. 1986, 51, 5270.
(18) For amination of dimethylalkylboranes with NH Cl see
We thank EPSRC (Grant EP/I038071/1) and the European
Research Council (FP7/2007-2013, ERC grant no. 246785) for
support. We thank Hazel Sparkes for X-ray analysis.
2
(a) Kabalka, G. W.; Wang, Z.; Goudgaon, N. M. Synth. Commun.
1
989, 19, 2409. For original reports see (b) Brown, H. C.; Heydkamp,
W. R.; Breuer, E.; Murphy, W. S. J. Am. Chem. Soc. 1964, 86, 3565.
c) Kabalka, G. W.; Sastry, K. A. R.; McCollum, G. W.; Yoshioka, H. J.
Org. Chem. 1981, 46, 4296.
19) Tertiary boronic esters have been aminated, after first conversion
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(
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(
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4) For example, tBu CiPr is believed to be the smallest saturated
4
77, 308.
(22) Hampel, C.; Werner, H.-J. J. Chem. Phys. 1996, 104, 6286.
(
3
(23) All three conformers have been studied and their energies are
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7) For discussion of relative migratory aptitudes see ref 6a and
given in the Supporting Information but only the conformer involving
Me migration with the lower energy and TS is given here.
(
(24) As shown in the Supporting Information, the relative free energy
of the key TSs is sensitive to the level of theory and the model used,
though in all calculations tBu migration is predicted to be favored (see
the Supporting Information). Indeed, the 0.2 kcal mol free energy gap
obtained with our “best” level of theory, using a truncated model of the
carbamate group, is the smallest gap obtained. Dispersion-corrected
DFT and use of a larger model both lead to larger energy gaps.
5
−1
(
(25) Robiette, R.; Fang, G. Y.; Harvey, J. N.; Aggarwal, V. K. Chem.
Commun. 2006, 741.
(
(
a) Aggarwal, V. K.; Fang, G. Y.; Ginesta, X.; Howells, D. M.; Zaja, M.
D
dx.doi.org/10.1021/ja509029h | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX