A R T I C L E S
Liang et al.
iodine(III) reagents of general formula PhIdNR which are now
easily handled.12 Rhodium(II) complexes have been found to
be the catalysts of choice to perform amination of various Cs
H bonds11b,12b,13 but ruthenium,12a,14 manganese,12a,14a,b,15 cop-
per,16 palladium,17 and silver18 based systems can also be used.
Nevertheless, despite this plethora of nitrene precursors and
transition metal catalysts, the efficiency of the subsequent Cs
H functionalization is almost always dependent upon the
involvement of an internal tether. While intramolecular CsH
amination is now a well-established methodology that has found
applications in total synthesis,19 the intermolecular version, by
contrast, suffers from being low yielding20 and limited in scope
to benzylic positions and cyclic ethers. Moreover, the rare
examples of enantioselective intermolecular nitrene CsH inser-
tions reported so far involve substrates used in excess. This work
therefore reports our recent efforts aimed at developing a
catalytic stereoselectiVe intermolecular CsH amination of
Various types of hydrocarbons used in stoichiometric amounts.
The high reactivity of the system based on cooperative effects
between a chiral rhodium(II) complex 1 and a sulfonimidamide
2 is one of the key elements allowing the efficient selective
CsH functionalization of benzylic and allylic substrates as well
as simple alkanes.
Figure 1. Diastereoselective rhodium-catalyzed benzylic C-H amination
using sulfonimidamide 2a.
organic synthesis.22 Recent development of simple methodolo-
gies for the in situ generation of iminoiodanes12 from various
nitrogen sources (i.e., sulfonamides, sulfamates, or carbamates)
prompted us to apply these conditions to sulfonimidamides. We
were thus very pleased to observe that, in our hands, these
reagents appear to be highly useful for the generation of chiral
nitrenes and their subsequent catalytic transfer. While their use
in the copper-catalyzed aziridination of olefins met with limited
success,23 the combination of the enantiomerically pure sulfon-
imidamide (S)-2a with the chiral rhodium(II) complex [Rh2-
{(S)-nttl}4] 1a as catalyst allowed us to discover a highly
efficient diastereoselective intermolecular C-H amination with
the C-H bond-containing substrate being the limiting compo-
nent (Figure 1).24
This efficient transformation is the consequence of an initial
screening of various reaction parameters using tetrahydronaph-
thalene 3a as a test substrate (see Supporting Information). We
thus found suitable conditions that involve use of 1.4 equiv of
the commercially available bis(tert-butylcarbonyloxy)iodosyl-
benzene PhI(OCOt-Bu)2 in a 3:1 mixture of 1,1,2,2-tetrachlo-
roethane/MeOH at -35 °C.24 Dichloromethane can also be used
instead of (Cl2CH)2, but yields are lower. The combination of
a halogenated solvent with methanol provides a completely
homogeneous reaction medium. Methanol allows solubilization
of the sulfonimidamide, but its compatibility with the catalytic
nitrene transfer is clearly unexpected (Vide infra). As far as the
oxidizing reagent is concerned, use of a slight excess of the
soluble PhI(OCOt-Bu)2 was shown to give higher yields than
those observed with the more commonly used PhI(OAc)2 and
PhIdO. Increasing the amount of PhI(OCOt-Bu)2 up to 2 equiv
does not improve the yields significantly (Vide infra), while
lengthening reaction times does.
Results and Discussion
Initial Results. Sulfonimidamides are analogues of sulfona-
mides in which one of the oxygen atoms of the sulfonyl moiety
has been replaced by a nitrogen group thereby making these
sulfur(VI) compounds chiral. They were first described by
Levchenko in the early 1960s21 but rarely used since then in
(12) (a) Yu, X.-Q.; Huang, J.-S.; Zhou, X.-G.; Che, C.-M. Org. Lett. 2000, 2,
2233-2236. (b) Espino, C. G.; Du Bois, J. Angew. Chem., Int. Ed. 2001,
40, 598-600. (c) Dauban, P.; Sanie`re, L.; Tarrade, A.; Dodd, R. H. J. Am.
Chem. Soc. 2001, 123, 7707-7708.
(13) (a) Na¨geli, I.; Baud, C.; Bernardinelli, G.; Jacquier, Y.; Moran, M.; Mu¨ller,
P. HelV. Chim. Acta 1997, 80, 1087-1105. (b) Fruit, C.; Mu¨ller, P. HelV.
Chim. Acta 2004, 87, 1607-1615. (c) Fruit, C.; Mu¨ller, P. Tetrahedron:
Asymmetry 2004, 15, 1019-1026. (d) Espino, C. G.; Wehn, P. M.; Du
Bois, J. J. Am. Chem. Soc. 2001, 123, 6935-6936. (e) Wehn, P. M.; Lee,
J.; Du Bois, J. Org. Lett. 2003, 5, 4823-4826. (f) Kim, M.; Mulcahy, J.
V.; Espino, C. G.; Du, Bois, J. Org. Lett. 2006, 8, 1073-1076. (g) Fiori,
K. W.; Du Bois, J. J. Am. Chem. Soc. 2007, 129, 562-568. (h) Yamawaki,
M.; Tsutsui, H.; Kitagaki, S.; Anada, M.; Hashimoto, S. Tetrahedron Lett.
2002, 43, 9561-9564. (i) Reddy, R. P.; Davies, H. M. L. Org. Lett. 2006,
8, 5013-5016.
(14) (a) Zhou, X.-G.; Yu, X.-Q.; Huang, J.-S.; Che, C.-M. Chem. Commun.
1999, 2377-2378. (b) Liang, J.-L.; Yuan, S.-X.; Huang, J.-S.; Yu, W.-Y.;
Che, C.-M. Angew. Chem., Int. Ed. 2002, 41, 3465-3468. (c) Liang, J.-
L.; Huang, J.-S.; Yu, X.-Q.; Zhu, N.; Che, C.-M. Chem.sEur. J. 2002, 8,
1563-1572. (d) Liang, J.-L.; Yuan, S.-X.; Huang, J.-S.; Che, C.-M. J. Org.
Chem. 2004, 69, 3610-3619.
(15) Kohmura, Y.; Katsuki, T. Tetrahedron Lett. 2001, 42, 3339-3342.
(16) (a) Fructos, M. R.; Trofimenko, S.; Mar Diaz-Requejo, M.; Perez, P. J. J.
Am. Chem. Soc. 2006, 128, 11784-11791. (b) He, L.; Yu, J.; Zhang, J.;
Yu, X.-Q. Org. Lett. 2007, 9, 2277-2280.
Under these conditions, very good yields up to 93% but also
excellent diastereoselectivities up to 99% could be obtained
(17) (a) Thu, H.-Y.; Yu, W.-Y.; Che, C.-M. J. Am. Chem. Soc. 2006, 128, 9048-
9049. (b) Dick, A. R.; Remy, M. S.; Kampf, J. W.; Sanford, M. S.
Organometallics 2007, 27, 1365-1370.
(22) (a) Takei, H.; Watanabe, I.; Mukaiyama, T. Bull. Chem. Soc. Jpn. 1965,
38, 1989-1993. (b) Jones, M. R.; Cram, D. J. J. Am. Chem. Soc. 1974,
96, 2183-2190. (c) Johnson, C. R.; Jonsson, E. U.; Bacon, C. C. J. Org.
Chem. 1979, 44, 2055-2061. (d) Okuma, K.; Koike, T.; Ohta, H. J. Org.
Chem. 1988, 53, 4190-4193. (e) Tsushima, S.; Yamada, Y.; Onami, T.;
Oshima, K.; Chaney, M. O.; Jones, N. D.; Swartzendruber, J. K. Bull. Chem.
Soc. Jpn. 1989, 62, 1167-1178. (f) Toth, J. E.; Grindey, G. B.; Ehlhardt,
W. J.; Ray, J. E.; Boder, G. B.; Bewley, J. R.; Klingerman, K. K.; Gates,
S. B.; Rinzel, S. M.; Schultz, R. M.; Weir, L. C.; Worzalla, J. F. J. Med.
Chem. 1997, 40, 1018-1025. (g) Cathers, B. E.; Schloss, J. V. Bioorg.
Med. Chem. Lett. 1999, 9, 1527-1532.
(23) (a) Di Chenna, P.; Robert-Peillard, F.; Dauban, P.; Dodd, R. H. Org. Lett.
2004, 6, 4503-4505. (b) Fruit, C.; Robert-Peillard, F.; Bernardinelli, G.;
Mu¨ller, P.; Dodd, R. H.; Dauban, P. Tetrahedron: Asymmetry 2005, 16,
3484-3487. See also: (c) Leca, D.; Toussaint, A.; Mareau, C.; Fensterbank,
L.; Lacoˆte, E.; Malacria, M. Org. Lett. 2004, 6, 3573-3575.
(24) Liang, C.; Robert-Peillard, F.; Fruit, C.; Mu¨ller, P.; Dodd, R. H.; Dauban,
P. Angew. Chem., Int. Ed. 2006, 45, 4641-4644.
(18) (a) Cui, Y.; He, C. Angew. Chem., Int. Ed. 2004, 43, 4210-4212. (b) Li,
Z.; Capretto, D. A.; Rahaman, R.; He, C. Angew. Chem., Int. Ed. 2007,
46, 5184-5186.
(19) For some recent relevant applications in total synthesis, see: (a) Hinman,
A.; Du Bois, J. J. Am. Chem. Soc. 2003, 125, 11510-11511. (b) Fleming,
J. J.; McReynolds, M. D.; Du Bois, J. J. Am. Chem. Soc. 2007, 129, 9964-
9975. (c) Trost, B. M.; Gunzner, J. L.; Dirat, O.; Rhee, Y. H. J. Am. Chem.
Soc. 2002, 124, 10396-10415. (d) Huang, H.; Panek, J. S. Org. Lett. 2003,
5, 1991-1993. (e) Parker, K. A.; Chang, W. Org. Lett. 2005, 7, 1785-
1788.
(20) Development of the highly reactive rhodium(II) complex Rh2(esp)2 has
allowed circumvention of this lack of reactivity in the case of benzylic
positions. See ref 13g and: Espino, C. G.; Fiori, K. W.; Kim, M.; Du Bois,
J. J. Am. Chem. Soc. 2004, 126, 15378-15379.
(21) (a) Levchenko, E. S.; Derkach, N. Y.; Kirsanov, A. V. Zh. Obshch. Khim.
1962, 32, 1208-1212. (b) Levchenko, E. S.; Markovskii, L. N.; Sher-
molovich, Yu. G. Zh. Org. Khim. 2000, 36, 167-181.
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