Bruce H. Lipshutz et al.
COMMUNICATIONS
mercially sold KOTMS,[21] however, decreased the re-
ACHTUNGTRENaNGNU mines is ongoing, as are studies on related couplings
action time with KOH/t-BuOH from six to three with aryl chlorides.
hours. A more remarkable result was observed upon
addition of branched silanol 8[22] (i.e., TIPS-OH, also
an item of commerce):[23] coupling to the desired di- Experimental Section
ACHTUNGTRENNUNGarylamine 6 was complete in <30 min. The pro-
nounced effect of this additive, in anion form Representative Procedure A for Aryl Aminations:
(Table 1, entries S, T), appears to be due to its poten- N-(4-Methoxyphenyl)-p-toluidine (Table 1, Entry J)
tial as a phase-transfer agent according to Soder-
Inside a dry box, to a 5-mL round-bottom flask equipped
with a stir bar and fitted with a rubber septum under argon
quist,[22] in this case shuttling protons between the
inside of the micelle (from the amine) to the excess
KOH in the water surrounding the nanoparticles.
Lastly, phenolic derivatives as leaving groups were
also investigated. Both triflates and less expensive,
more lipophilic perfluorooctanesulfonates[24] could be
aminated at room temperature in PTS/H2O using p-
fluoroaniline as a model amine (Scheme 5). Et3N as
base appeared to minimize competing hydrolysis of
either type of sulfonate ester, seen to varying extents
in the presence of KO-t-Bu alone. Higher yields were
obtained with the more highly fluorinated derivative
in both cases.
were sequentially charged with [(p-allyl)PdCl]2 (2.1 mg,
0.006 mmol), cBRIDP (2) (7.6 mg, 0.022 mmol), 95% KO-t-
Bu (184 mg, 1.56 mmol), and p-toluidine (137 mg,
1.23 mmol). Outside the dry box, under a positive flow of
argon were added via syringe sequentially, degassed water
(0.8 mL), degassed 10 wt% PTS solution (0.2 mL) (to give a
degassed 2 wt% PTS solution (1.0 mL)), and 4-bromoanisole
(130 mL, 1.04 mmol). The milky reaction mixture was stirred
under argon at room temperature. After complete consump-
tion of the aryl bromide was observed by GC analysis
(21 h), the mixture was diluted with brine and extracted
with EtOAc (4ꢂ). The combined organic extracts was dried
over anhydrous Na2SO4, filtered, and concentrated by rotary
evaporation to give the crude residue. Purification by silica
gel chromatography (eluent: gradient from hexanes to 3%
EtOAc/hexanes) afforded the titled product as an off-white
solid; yield: 218 mg (99%); mp 83–848C. 1H NMR
(400 MHz, CDCl3) values match previously reported spectra
data.[3] The polar PTS is completely separated at the top of
the silica column.
Acknowledgements
Financial support provided by Zymes, LLC is warmly ac-
knowledged with thanks. We are indebted to Takasago for a
generous supply of the cBRIDP ligand (2).
References
[1] J. P. Wolfe, H. Tomori, J. P. Sadighi, J. Yin, S. L. Buch-
wald, J. Org. Chem. 2000, 65, 1158–1174.
[2] M. Kienle, S. R. Dubbaka, K. Brade, P. Knochel, Eur. J.
Org. Chem. 2007, 4166–4176.
[3] Q. Shen, T. Ogata, J. F. Hartwig, J. Am. Chem. Soc.
2008, 130, 6586–6596.
[4] a) E. A. B. Kantchev, C. J. OꢀBrien, M. G. Organ, Aldri-
chimica Acta 2006, 39, 97–110; b) M. G. Organ, M.
Abdel-Hadi, S. Avola, I. Dubovyk, N. Hadei, E. A. B.
Kantchev, C. J. OꢀBrien, M. Sayah, C. Valente, Chem.
Eur. J. 2008, 14, 2443–2452; c) D. S. Surry, S. L. Buch-
wald, Angew. Chem. 2008, 120, 6438–6461; Angew.
Chem. Int. Ed. 2008, 47, 6338–6361; d) J. F. Hartwig,
Acc. Chem. Res. 2008, 41, 1534–1544.
[5] Green Chemistry and Catalysis, (Eds.: R. A. Sheldon, I.
Arends, U. Hanefeld), Wiley-VCH, Weinheim, 2007.
[6] a) X. Huang, K. W. Anderson, D. Zim, L. Jiang, A.
Klapars, S. L. Buchwald, J. Am. Chem. Soc. 2003, 125,
Scheme 5. Aminations of fluorosulfonate derivatives.
In summary, a new method has been developed
that allows for aminations of aryl bromides with aryl-
amines to be conducted in the absence of both heat
and organic solvent. These mild conditions arise in
part due to micellar effects based on PTS,[11] an am-
phiphile that continues to demonstrate considerable
applicability to transition metal-catalyzed cross-cou-
plings.[25] Further work on aminations with alkyl-
1720
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2009, 351, 1717 – 1721