Imidazolylsulfonates: Electrophilic partners in cross-coupling reactions

Article abstract of DOI:10.1021/ol802381k

Aryl imidazolylsulfonates participate as electrophilic coupling partners in palladium-mediated cross-coupling reactions. The aryl imidazolylsulfonates display good stability while maintaining good reactivity in a variety of palladium-catalyzed coupling reactions. Imidazolylsulfonates are a practical and economic alternative to triflates.

Full text of DOI:10.1021/ol802381k

ORGANIC
LETTERS
2009
Vol. 11, No. 7
1463-1466
Imidazolylsulfonates: Electrophilic
Partners in Cross-Coupling Reactions
Jennifer Albaneze-Walker,* Ravinder Raju, Jennifer A. Vance,
Andrew J. Goodman, Michael R. Reeder, Jing Liao, Mathew T. Maust,
Patrick A. Irish, Peter Espino, and David R. Andrews
Synthetic Chemistry, Chemical & Physical Sciences, Schering-Plough Corporation,
1011 Morris AVenue, Union, New Jersey 07083
jennifer.albaneze-walker@spcorp.com
Received October 15, 2008
ABSTRACT
Aryl imidazolylsulfonates participate as electrophilic coupling partners in palladium-mediated cross-coupling reactions. The aryl imidazolyl-
sulfonates display good stability while maintaining good reactivity in a variety of palladium-catalyzed coupling reactions. Imidazolylsulfonates
are a practical and economic alternative to triflates.
Triflates have long been used in phenol activation toward
cross-coupling reactions due to their superior performance
as electrophilic coupling partners.1 Excellent reactivity,
however, comes at the expense of stability, and triflates can
often suffer from instability. This problem coupled with the
high cost of trifluoromethanesulfonic anhydride and triflimide
reagents, from which triflates are made, limits their usefulness
on larger scales. Recently, the palladium-catalyzed cross-
coupling repertoire has been expanded to include aryl
tosylates and aryl mesylates as viable electrophilic partners.2
Aryl tosylates and mesylates are easily prepared and exhibit
better stability than triflates and thus are more easily stored
and handled. However, reactivity is diminished in palladium-
mediated coupling reactions. Successful couplings of these
less reactive sulfonates typically require a bulky electron-
rich phosphine ligand on the palladium center2a and can
exhibit marked solvent dependence or substrate specificity.
coupling reactions. Imidazolesulfonates exhibit markedly
improved reactivity over aryl tosylates and improved stabil-
ity, handling properties, and cost over aryl triflates.
The imidazolylsulfonate moiety was introduced by the
Hanessian group as a superb leaving group for sugar
compounds.3 Since then, the imidazolylsulfonate moiety has
been reported primarily in the carbohydrate and nucleoside
literature as a useful electrophile in several total syntheses
of carbohydrate-containing natural products.4 The imida-
zolylsulfonate has also been used in the syntheses of a
cyclodextrin and of substituted estradiol compounds.5 More
recently, imidazole-1-sulfonyl azide hydrochloride has been
introduced as a useful and practical diazo donor reagent that
mimics trifluoromethanesulfonyl azide in reactivity.6
Given the versatile properties of the imidazolylsulfonate
group, we reasoned that aryl imidazolylsulfonates would
participate as electrophilic coupling partners in palladium-
catalyzed coupling reactions. We anticipated that imida-
zolylsulfonates would provide enough increased stability and
ease of handling to be useful on scale without sacrificing a
drastic loss in reactivity compared to aryl triflates.
We report herein the first use of imidazolylsulfonates as
effective electrophilic coupling partners in metal-catalyzed
(1) (a) Scott, W.; Crisp, G.; Stille, J. K. J. Am. Chem. Soc. 1984, 106,
4630–4632. (b) For a review of triflate chemsitry, see: Baraznenok, I.;
Nenajdenko, V.; Balenkova, E. Tetrahedron 2000, 56, 3077–3119. (c) For
a review of heterocycle synthesis via cross-coupling of triflates, see: Gilson,
Z.; Larock, R. Chem. ReV. 2006, 106, 4644–4680.
Hanessian et al. reported two methods for the generation
of imidazolylsulfonates. Method A employs a sequential
reaction of the hydroxyl compound with sulfuryl chloride
10.1021/ol802381k CCC: $40.75
Published on Web 03/12/2009
2009 American Chemical Society

followed by addition of a large excess of imidazole. In
Method B, alkoxide formation with sodium hydride was
followed by reaction with the commercially available crystal-
line reagent 1,1′-sulfonyldiimidazole.4a
Method A was used initially to generate the aryl imida-
zolylsulfonates (Table 1, entries 1-3 and 7). Yields were
metric amount of cesium carbonate in 20 vol of THF at room
temperature. Most reactions were complete within 16 h, and
yields of the desired imidazolysulfonates improved to 85%
or greater in all cases (Table 1). o-Methyl groups do not
hinder the reaction (entry 5), and both electron-withdrawing
and electron-releasing groups are well tolerated.
With a general method in hand to make the required aryl
imidazolylsulfonates, we next turned our attention to their
performance in cross-coupling reactions. The aryl imida-
zolylsulfonates were subjected to typical Suzuki-Miyaura
and Negishi-type conditions, and the expected products were
isolated in good yields (Scheme 1).8 A variety of palladium
Table 1. Synthesis of Imidazolylsulfonates
Scheme 1
.
Imidazolylsulfonates in Suzuki-Miyaura and
Negishi Cross-Coupling Reactionsa
a Method A conditions: sulfuryl chloride then imidazole in CH2Cl2, 0
°C to rt. b Method B conditions: 1,1′-sulfonyldiimidazole plus Cs2CO3 in
THF at rt. c Method A produced 2,4-dichloronaphthol as the only product.
a Isolated yields were not optimized.
fair to moderate for the phenols, but no desired imidazolyl-
sulfonate product was formed from 1-naphthol (entry 6). Not
surprisingly, chlorination is a competitive pathway under
these conditions.
A screen of alternatives to replace sodium hydride, called
for in Method B, revealed cesium carbonate as the most
effective base. Optimal conditions employ a slight excess
of the reagent 1,1′-sulfonyldiimidazole7 with a substoichio-
catalysts were used successfully to effect the couplings. The
reactions were achieved in a variety of solvents as well.
Addition of lithium chloride showed no benefit or detriment:
yield and rate were essentially unchanged in THF.9 More-
over, the aryl imidazolylsulfonates exhibited good shelf life;
coupling yields were not reduced by using imidazolylsul-
fonates that had been stored at ambient temperature for 7
months.
1464
Org. Lett., Vol. 11, No. 7, 2009

Preliminary comparative rate studies revealed that the
reactivity of naphthyl imidazolylsulfonates is similar to that
of naphthyl triflates (Scheme 2). The conversion rate is
Imidazolylsulfonates are also useful intermediates for
functional group transformation of the phenol (Scheme 3).
Scheme 3
.
Hydrogenolysis and Carbonylation Reactions of
2-Naphthylimidazolylsulfonate
Scheme 2. Suzuki Cross-Coupling Reactivity Comparison:
Triflate versus Imidazylate versus Tosylate
Reduction of 2-naphthol imidazolylsulfonate was achieved
under very mild hydrogenolysis conditions to produce
naphthalene in good yield. Palladium-catalyzed carbonylation
to generate the ester also proceeded in excellent yield under
exceedingly mild conditions.10
An important added benefit to using imidazolylsulfonates
is the inherent potential for self-destruction of the cross-
coupling byproduct imidazolesulfonic acid. Recently, there
has been a greater regulatory focus on alkyl and aryl
sulfonates as potential genotoxic impurities (PGIs).11 The
byproduct of the imidazolylsulfonate cross-coupling is imi-
dazolesulfonic acid (Scheme 4).12 Unlike tosic, methane-
sulfonic, and triflic acids, imidazolesulfonic acid hydrolyzes
in the presence of water and acid to produce imidazole and
sulfuric acid, and thus the potential formation of alkyl or
aryl sulfonates from the residual sulfonic acid is eliminated.
The imidazolylsulfonate moiety is conveniently designed for
degradation under aqueous and acidic conditions.
somewhat slower: the 2-naphthyl triflate conversion was 98%
in 30 min, whereas the analogous 2-nathphyl imidazolylsul-
fonate required 2.5 h to reach full conversion. In sharp
contrast, the 2-naphthyl tosylate analogue was inert under
the same conditions.
(2) (a) Roy, A.; Hartwig, J. J. Am. Chem. Soc. 2003, 125, 8704–8705.
(b) Nguyen, H.; Huang, X.; Buchwald, S. J. Am. Chem. Soc. 2003, 125,
11818–11819. (c) Zhang, L.; Meng, T.; Wu, J. J. Org. Chem. 2007, 72,
9346–9349. (d) Steinhuebel, D.; Baxter, J.; Palucki, M.; Davies, I. J. Org.
Chem. 2005, 70, 10124–10127. (e) Baxter, J.; Steinhuebel, D.; Palucki, M.;
Davies, I. Org. Lett. 2005, 7, 215–218. (f) Wu, J.; Zhu, Q.; Fathi, R.; Yang,
Z. J. Org. Chem. 2003, 68, 670–673. (g) Molander, G.; Yun, C. Tetrahedron
2002, 58, 1465–1470. (h) Ackermann, L.; Althammer, A. Org. Lett. 2006,
8, 3457–3460. (i) Huffman, M.; Yasuda, N. Synlett 1999, 471–473. (j) For
an example of Sonogashira coupling of a vinyl tosylate, see: Woo, J.;
Walker, S.; Faul, M. Tetrahedron Lett. 2007, 48, 5679–5682. (k) Fu, X.;
Zhang, S.; Yin, J.; Schumacher, D. Tetrahedron Lett. 2002, 43, 6673–6676.
(l) For reductive deoxygenation of aryl mesylate, see: Sajiki, H.; Mori, A.;
Mizusaki, T.; Ikawa, T.; Maegawa, T.; Hirota, K. Org. Lett. 2006, 8, 987–
990. (m) For an amination of mesylates, see: So, C.; Zhou, Z.; Lau, C.;
Kwong, F. Angew. Chem., Int. Ed. 2008, 47, 1–6.
In conclusion, we have demonstrated the practical and
scalable synthesis of aryl imidazolylsulfonates and their
(6) Goddard-Borger, E.; Stick, R. Org. Lett. 2007, 9, 3797–3800.
(7) (a) Staab, H.; Wendel, K. Angew. Chem. 1961, 73, 26. (b) Staab,
H.; Wendel, K. J. Liebigs Ann. Chem. 1966, 694, 86–90. (c) 1,1′-
Sulfonyldiimidazole has been used recently as an imidazole transfer reagent;
see: Keith, J. J. Org. Chem. 2008, 73, 327–330.
(8) (a) For recent reviews of the Suzuki-Miyaura coupling reaction see:
Doucet, H. Eur. J. Org. Chem. 2008, 7, 1133-1155 and(b) Alonso, F.;
Beletskaya, I.; Yus, M. Tetrahedron 2008, 64, 3047–3101. (c) For a recent
review of Negishi couplings, see: Negishi, E.-I. Bull. Chem. Soc. Jpn. 2007,
80, 233–257. (d) Reeder, M.; Gleaves, H.; Hoover, S.; Imbordino, R.
Pangborn. J. Org. Proc. Res. DeV. 2003, 7, 696–699. (e) Anderson, B.;
Becke, L.; Booher, R.; Flaugh, M.; Harn, N.; Kress, T.; Varie, D.; Wepsiec,
J. J. Org. Chem. 1997, 62, 8364–8369. (f) Anderson, B.; Harn, N. Synthesis
1996, 5, 583–585. (g) Crowe, E.; Hossner, F.; Hughes, M. Tetrahedron
1995, 51, 8889–8890.
(3) (a) Hanessian, S.; Vate`le, J.-M. Tetrahedron Lett. 1981, 37, 3579–
3582. (b) Vate`le, J.-M.; Hanessian, S. Tetrahedron 1996, 52, 10557–10568,
and references therein.
(4) (a) Ingram, L.; Taylor, S. Angew. Chem., Int. Ed. 2006, 45, 3503–
3506. (b) Beaudion, S.; Kinsey, K.; Burns, J. J. Org. Chem. 2003, 68, 115–
119. (c) Ma, T.; Pai, B.; Zhu, Y.; Lin, J.; Shanmuganathan, K.; Du, J.;
Wang, C.; Kim, H.; Newton, M.; Cheng, Y.; Chu, C. J. Med. Chem. 1996,
39, 2835–2843. (d) Ahmed, F.; David, S.; Vate`le, J.-M. Carbohydr. Res.
1986, 155, 19–31. (e) David, S.; Malleron, A.; Dini, C. Carbohydr. Res.
1989, 158, 193–200. (e) Duan, S.; Binkley, E.; Binkley, R. J. Carbohydr.
Chem. 1998, 17, 391–396. (f) Tann, C.; Brodfuehrer, P.; Brundidge, S.;
Sapino, C.; Howell, H. J. Org. Chem. 1985, 50, 3644–3647. (g) Chou, T.;
Becke, L.; O’Toole, J.; Carr, M.; Parker, J Tetrahedron Lett. 1996, 37,
17–20. (h) Alais, J; David, S. Carbohydr. Res. 1992, 230, 79–87. (i) Best,
W.; Macdonald, J.; Skelton, B.; Stick, R.; Tilbrook, D.; White, A. Can.
J. Chem. 2002, 80, 857–865. (j) Meloncelli, P.; Stick, R. Aust. J. Chem.
2006, 59, 827–833.
(9) (a) Scott, W.; Stille, J. K. J. Am. Chem. Soc. 1986, 108, 3033–3040.
(b) Echavarren, A.; Stille, J. K. J. Am. Chem. Soc. 1987, 109, 5478–5486.
(c) Casado, A.; Espinet, P.; Gallego, A. J. Am. Chem. Soc. 2000, 122,
11771–11782.
(10) Albaneze-Walker, J.; Bazaral, C.; Leavey, T.; Dormer, P.; Murry,
J. Org. Lett. 2004, 6, 2097–2100.
(11) (a) Elder, D.; Teasdale, A.; Lipczynski, A. J. Pharm. Biomed. Anal.
2008, 46, 1–8. (b) Snodin, D. Reg. Toxicol. Pharm. 2006, 45, 79–90. (c)
Glowienke, S.; Frieauff, W.; Allmendinger, T.; Martus, H.-J.; Mueller, L.
Mutat. Res. 2005, 581, 23–34. (d) Committee for Medicinal Products
(CHMP); Guideline on the Limits of Genotoxic Impurities; European
Medicines Agency: London, 2008 (CPMP/SWP/5199/02, EMEA/CHMP/
QWP/251344/2006).
(5) (a) Teranishi, K.; Hisamatsu, M.; Yamada, T. Tetrahedron Lett. 2000,
41, 933–936. (b) Fevig, T.; Mao, M.; Katzenellenbogen, J. Steroids 1988,
51, 471–479. (d) Ahmed, F.; David, S.; Vate`le, J.-M. Carbohydr. Res. 1986,
155, 19–31.
(12) (a) Staab, H. Angew. Chem.m Int. Ed. Engl. 1962, 1, 351–367. (b)
Botchkavvieva, T; Passet, B. Zh. Obshch. Khim. 1983, 2221–2222.
Org. Lett., Vol. 11, No. 7, 2009
1465

Suzuki-Miyaura and Negishi-type couplings, as well as
participants in both hydrogenolysis and carbonylation reac-
tions. Imidazolylsulfonates are a practical and economical
alternative to triflates for a variety of palladium catalyzed
reactions. Further development of coupling reactions is
underway in our laboratories and will be reported in due
course.
Scheme 4
.
Degradation of Imidazolesulfonic Acid
Post-Coupling
Acknowledgment. We thank our colleagues Bruce A.
Pearlman, Donald Hou, and Guy Gloor for many helpful
discussions and Ilia Zavialov for help with translation of the
Russian reference.
Supporting Information Available: Experimental and
characterization data details. This material is available free
of charge via the Internet at http://pubs.acs.org.
utility in palladium-mediated reactions. Imidazolylsulfonates
act as fully competent electrophilic coupling partners in
OL802381K
1466
Org. Lett., Vol. 11, No. 7, 2009