Journal of the American Chemical Society
Page 4 of 5
B.; GarciaꢀRubia, A.; Hayter, B.R.; Willis, M.C. Org. Biomol. Chem.
2012, 10, 4007.
ASSOCIATED CONTENT
1
2
3
4
5
6
7
8
(13) (a) Shengqing, Y.; Wu, J. Chem. Comm. 2012, 48, 7753. (b)
Shengqing, Y.; Wu, J. Chem. Comm. 2012, 48, 10037.
(14) (a) Caddick, S.; Wilden, J. D.; Judd, D. B. Chem. Commun.
2005, 2727. (b) Wilden, J.D.; Geldeard, L.; Lee, C.C.; Judd, D.B.;
Caddick, S. Chem. Commun. 2007, 1074. (c) Bornholdt, J.; Fjaere,
K.W.; Felding, J.; Kristensen, J.L. Tetrahedron 2009, 65, 9280.
(15) Buncel, E. Chem. Rev. 1970, 70, 323.
(16) Phenyl chlorosulfate is prepared by reacting phenol SO2Cl2
and pyridine at ꢀ78 °C. Compound 2a is stable in neat form for at
least one year when stored at 4 °C.
(17) No reaction was observed when solutions of 4ꢀ
methoxyphenylboronic acid (1.5 equiv) and 2a (1.0 equiv) in toluꢀ
ene or 1,4ꢀdioxane were stirred at 110 °C for 24 h.
(18) Subjecting a phenyl sulfonate ester (3) to the reaction condiꢀ
tions in the presence of 2a and ArB(OH)2 resulted in complete
recovery of 3. See Supporting Information for details.
(19) An alternative mechanism might involve reversible oxidaꢀ
tive addition to 2a, with transmetallation occurring at the −OPh
group of 7 in preference to the −Cl group of the related PdꢀCl speꢀ
cies. Oxidative addition is typically considered an irreversible proꢀ
cess, although examples of reductive elimination of aryl halides
have been reported. See: (a) Roy, A. H.; Hartwig, J. F. Organome-
tallics 2004, 23, 1533. (b) Newman, S.G.; Lautens, M. J. Am.
Chem. Soc. 2010, 132, 11416.
(20) Alkoxoꢀ and (phenoxo)Pd(II) complexes are known to unꢀ
dergo efficient transmetallation without the aid of base. For reviews
and discussions, see: (a) Miyaura, N. J. Organomet. Chem. 2002,
653, 54. (b) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(21) (a) Buncel, E.; Raoult, A. Can. J. Chem. 1972, 50, 1907. (b)
Buncel, E.; Choong, L.I.; Raoult, A. J. Chem. Soc., Perkin Trans. II,
1972, 691.
Experimental procedures and characterization data for all
compounds. This material is available free of charge via the
AUTHOR INFORMATION
Corresponding Author
Notes
The authors declare the following competing financial interꢀ
est(s): MIT has patents on ligands that are described in the
paper from which S.L.B. receives royalty payments.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ACKNOWLEDGMENT
We thank the National Institutes of Health for financial
support of this project (GM58160) and a fellowship to
J.R.D. (1F32GM099202). The Varian 300 and 500 MHz
NMR spectrometers used for portions of this work were
purchased with funds from NSF (Grants CHEꢀ9808061 and
DBIꢀ9729592).
REFERENCES
(
1) Drews, J. Science 2000, 287, 1960.
(2) (a) Bartholow, M. Top 200 Drugs of 2011. Pharmacy Times.
2/Topꢀ200ꢀDrugsꢀofꢀ2011. (b) For a list of top drugs by year see:
http://cbc.arizona.edu/njardarson/group/topꢀpharmaceuticalsꢀ
poster.
(3) Anderson, K. K. In Sulfonic Acids and Their Derivatives in
Comprehensive Organic Chemistry; Barton, D. H. R., Ollis, W. D.,
Jones, D. N., Eds.; Pergamon Press, Oxford, 1979; Vol. 3, pp 331ꢀ
350.
(4) Cremlyn. R.J. Chlorosulfonic Acid: A Versatile Reagent;
Royal Society of Chemistry: Cambridge, 2002; pp 7ꢀ21.
(5) (a) Baharami, K.; Khodaei, M.M.; Khaledian, D. Tetrahedron
Lett. 2012, 53, 354. (b) Prakash, G.K.S.; Mathew, T.; Olah, G.A. J.
Org. Chem. 2007, 72, 5847. (c) Wright, S.W.; Hallstrom, K.N. J.
Org. Chem. 2006, 71, 1080.
(6) (a) Percec, V.; Bera, T.K.; De, B.B.; Sanai, Y.; Smith, J.;
Holerca, M.N.; Barboiu, B.; Grubbs, B.B.B.; Fréchet, JMJ. J. Org.
Chem. 2001, 66, 2104. (b) (a) Watson, R. J.; Batty, D.; Baxter, A.
D.; Hannah, D. R.; Owen, D. A.; Montana, J. G. Tetrahedron Lett.
2002, 43, 683.
(7) (a) Alapafuja, S.O.; Nikas, S.P.; Shukla, V.G.; Papanastasiou,
I.; Makriyannis, A. Tetrahedron Lett. 2009, 50, 7028. (b) Bahrami,
K.; Khodaei, M. M.; Soheilizad, M. J. Org. Chem. 2009, 74, 9287.
(8) (a) Pandya, R.; Murashima, T.; Tedeschi, L.; Barret, A.G.M. J.
Org. Chem. 2003, 68, 8274. (b) Woolven, H.; GonzálezꢀRodrígues,
C.; Marco, I.; Thompson, A.L.; Willis, M.C. Org. Lett. 2011, 13,
4876. (c) Monovich, L.G.; Tommasi, R.A.; Fujimoto, R.A.; Blancuzꢀ
zi, V.; Clark, K.; Cornell, W.D.; Doti, R.; Doughty, J.; Fang, J.; Farꢀ
ley, D.; Fitt, J.; Ganu, V.; Goldberg, R.; Goldstein, R.; Lavoie, S.;
Kulathila, R.; Macchia, W.; Parker, D.T.; Melton, R.; O’Byrne, E.;
Pastor, G.; Pellas, T.; Quadros; E.; Reel, N.; Roland, D.M.; Sakane,
Y.; Singh, H.; Skiles, J.; Somers, J.; Toscano, K.; Wigg, A.; Zhou, S.;
Zhu, L.; Shieh, W.; Xue, S.; McQuire, L.W. J. Med. Chem. 2009,
52, 3523.
(9) (a) Ho, D.K.H.; Chan, L.; Brennan, P.E. Tetrahedron Lett.
2011, 52, 820. (b) Bonk, J. D.; Amos, D. T.; Olson, S. J. Synth.
Commun. 2007, 37, 2039.
(10) Diazonium salts have been used as direct precursors to sulꢀ
fonyl chlorides. For a recent example, see: MaletꢀSanz, L.; Madrzak,
J.; Ley, S.V.; Baxendale; I.R. Org. Biomol. Chem. 2010, 8, 5324.
(11) Alternatively, sulfonyl compounds can be prepared in oneꢀ
pot from Grignard additions to SO2 (see refs 8aꢀb), but subsequent
chlorination requires SO2Cl2, which readily chlorinates aromatic
rings.
(22) Bruno, N. C., Tudge, M. T, Buchwald, S. L. Chem.
Sci. 2012, 4, 916.
(23) For examples of crossꢀcouplings using XPhos precatalysts,
see: (a) Kinzel, T., Zhang, Y., and Buchwald, S.L. J. Am. Chem.
Soc. 2010, 132, 14073. (b) Oberli, M.A., and Buchwald, S.L. Org.
Lett. 2012, 14, 4606.
(24) Similarly, little to no product was observed using SPhos or
RuPhos ligands. For a review of Suzuki−Miyaura reactions employꢀ
ing dialkylbiaryl phosphine ligands, see: Martin, R.; Buchwald, S.L.
Acc. Chem. Res. 2008, 41, 1461.
(25) Both Pd(0) and phosphine ligands can potentially react with
4; thus to limit product decomposition and promote complete conꢀ
version of 2a, we chose to increase the reaction temperatures acꢀ
cordingly rather than adjust the respective catalyst loadings.
(26) Electronꢀpoor arylboronic acids typically undergo
transmetallation at a slower rate than electronꢀneutral and elecꢀ
tronꢀrich arylboronic acids.
(27) The volatility of 4dꢀ4i may also contribute to lower yields.
(28) The stoichiometry of the amine can be reduced to 1.2 equivꢀ
alents if DIPEA is used as a sacrificial base. See conditions for
product 5d (Table 3).
(29) Currently, boronic acids derived from nitrogen heterocycles
do not couple in useful yields. This inefficiency is due to deboronaꢀ
tion of the starting material and/or the instability of the correꢀ
sponding sulfonyl chlorides. See: Caldwell, W.T.; Kornfeld, E.C. J.
Am. Chem. Soc. 1950, 72, 4890.
(30) The order of reactivity of electrophiles for SuzukiꢀMiyaura
crossꢀcoupling is: ArI > ArSO2Cl > ArBr >> ArCl (see ref 32c).
(31) Aryl sulfonyl chlorides have been used as precursors to diꢀ
aryl sulfones. See: Bandgar, B.P.; Bettigeri, S.V.; Phopase; J. Org.
Lett. 2004, 6, 2105.
(32) For examples of desulfonylative crossꢀcouplings of sulfonyl
chlorides to form C—C bonds, see: (a) Miura, M.; Itoh, K. Chem.
Lett. 1989, 18, 77. (b) Dubbaka; S.R.; Vogel; P. J. Am. Chem. Soc.
2003, 125, 15292. (c) Dubbaka; S.R.; Vogel; P. Org. Lett. 2004, 6,
95. (d) Dubbaka; S.R.; Vogel; P. Tetrahedron Lett. 2006, 47, 3345.
(33) We observe homocoupling (< 15% biaryl) of certain elecꢀ
tronꢀdeficient and orthoꢀsubstituted arylboronic acids (e.g. correꢀ
sponding to 5f and 5j). This side reaction may occur at the expense
of 2a via an oxidative addition/desulfonylation pathway.
(34) A control experiment in which 2c is introduced after comꢀ
plete conversion of 2b verified that 2c is not converted to 2b. See
Supporting Information for details.
(12) (a) Nguyen, B.; Emmet, E.J.; Willis, M.C. J. Am. Chem. Soc.
2010, 132, 16372. (b) Emmet, A.J.; RichardsꢀTaylor, C.S.; Nguyen,
ACS Paragon Plus Environment