Efficient diastereoselective intermolecular rhodium-catalyzed C-H amination

Article abstract of DOI:10.1002/anie.200601248

(Chemical Equation Presented) Successful matchmaking: The combination of a chiral nitrene precursor with a chiral rhodium(II) catalyst is the key factor that allows efficient intermolecular regioselective C-H amination. Good-to-excellent yields and excellent diastereoselectivities can be obtained with a stoichiometric amount of the C-H bond containing substrate. nttl = N-1,8-naphthoyl-tert-leucine.

Full text of DOI:10.1002/anie.200601248

Angewandte
Chemie
[
1]
of valuable building blocks from simple molecules. Consid-
ering the ubiquity of CÀH bonds in organic compounds,the
search for a process that allows their selective transformation
remains challenging. Methodologies have been recently
[
2]
[3]
[4,5]
developed for regioselective CÀC, CÀO, or CÀN
bond
[
6]
formations that have found applications in total synthesis.
In the case of CÀH amination,significant results have
been obtained by using transition-metal-catalyzed nitrene
[
5,7]
transfer that starts from iminoiodanes.
This field,pio-
[
8]
[9]
neered by Breslow and Mansuy, has progressed consid-
erably over the last five years with the discovery of new
[
5a,d,10]
methodologies for the generation
of these hypervalent
iodine(III) reagents in situ. Thus,PhI(OAc) -mediated CÀH
2
[
5a–c]
amination has been shown to be catalyzed by ruthenium,
[
5a]
[5d–g]
[5i]
manganese,
rhodium,
and silver
complexes with
sulfonamides,sulfamates,or carbamates as nitrene precur-
sors. However,although the intramolecular process occurs
efficiently,the intermolecular version suffers from low con-
versions or the need for a large excess of the starting alkane
[
1g,5a,b,h,11]
(5–100 equivalents) to obtain good yields.
The
involvement of transition-metal catalysts has also allowed
the development of enantioselective nitrene CÀH inser-
[
12]
tions.
Although good enantioselectivities have been
reported for intramolecular CÀH aminations,an excess of
Transition-Metal Catalysis
alkane in the intermolecular version is again required to reach
[
12a,b,g]
satisfactory selectivities.
It is therefore in this context
DOI: 10.1002/anie.200601248
that we report herein an efficient diastereoselective intermo-
lecular CÀH amination that occurs under stoichiometric
Efficient Diastereoselective Intermolecular
Rhodium-Catalyzed CÀH Amination**
conditions and starts from an enantiomerically pure nitrene
precursor (that is,( S)-N-(p-toluenesulfonyl)-p-toluenesulfon-
imidamide (1a)).
We recently reported the generation of chiral imino-
Chungen Liang, Fabien Robert-Peillard, Corinne Fruit,
Paul Müller,* Robert H. Dodd,* and Philippe Dauban*
[
13]
iodanes from sulfonimidamides in situ. It was found that
the nitrene intermediates generated from these chiral sul-
fur(VI) reagents are highly reactive species that add to
various olefins in the presence of copper(I) catalysts to afford
aziridines in good yields but with moderate diastereoselecti-
In memory of Pierre Potier
[
13a]
The selective functionalization of a CÀH bond is an area of
vities.
Rhodium(II) complexes have also been found to
intense investigation as such a reaction leads to the formation
catalyze the aziridination of alkenes,and in particular the use
of chiral ligands has been shown to improve diastereoselecti-
[
13b]
vities.
Given the greater ability of rhodium(II) tetracar-
[
*]Dr. C. Fruit, Prof. Dr. P. Müller
Department of Organic Chemistry
University of Geneva
boxylates to mediate CÀH amination and the high reactivity
of sulfonimidamide-derived nitrenes,we thus decided to
combine these properties with the aim of developing an
efficient intermolecular CÀH amination (Scheme 1).
30 quai Ernest Ansermet, 1211 Geneva 4 (Switzerland)
Fax: (+41)223-287-396
E-mail: paul.muller@chiorg.unige.ch
Initial experiments were aimed at screening various
rhodium(II) complexes and enantiomerically pure substituted
Dr. C. Liang, F. Robert-Peillard, Dr. R. H. Dodd, Dr. P. Dauban
Institut de Chimie des Substances Naturelles
CNRS
Avenue de la Terrasse, 91198 Gif-sur-Yvette (France)
Fax: (+33)1-6907-7247
sulfonimidamides 1 in the presence of PhI(OAc) and MgO in
2
[
5d]
dichloromethane. We found that a combination of (À)-(S)-
N-(p-toluenesulfonyl)-p-nitrobenzenesulfonimidamide
[
13a,b,14]
(1b)
and the chiral rhodium carboxylate catalysts
E-mail: dodd@icsn.cnrs-gif.fr
dauban@icsn.cnrs-gif.fr
[
**]We wish to thank the Institut de Chimie des Substances Naturelles
and the Swiss National Science Foundation for financial support
and fellowships. Support and sponsorship concerted by COST
Action D24 “Sustainable Chemical Processes: Stereoselective
Transition Metal-Catalyzed Reactions” are kindly acknowledged.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Scheme 1. Intermolecular CÀH amination under stoichiometric condi-
tions.
Angew. Chem. Int. Ed. 2006, 45, 4641 –4644
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4641

Communications
[
15]
[
Rh {(S)-nttl} ] (2a;
nttl = N-1,8-naphthoyl-tert-leucine;
and selectivities. On the other hand,the mismatched combi-
nation of the enantiomer (R)-1a and catalyst 2a gives ent-4a
in only 10% yield with 53% de,whereas the same reaction
starting from racemic 1a affords 4a in 33% yield with 97%
2
4
Scheme 2) gave good results with indane 3 as a model
substrate. Starting with one equivalent of 3,the p-nitro
analogue of the CÀH amination product 3a was isolated in
[
21]
4
5% yield and with > 90% diastereoisomeric excess,as
de.
It should also be mentioned that the presence of
1
estimated by H NMR spectroscopic analysis. However,when
applied to other substrates,such as tetrahydronaphthalene 4,
these conditions led to lower yields.
methanol has a major influence on the matched effect. This
result was applied to the preparation of ent-4a,obtained in
83% yield with 99% de (entry 3) from the matched combi-
nation of the sulfonimidamide (R)-1a and the rhodium
[
22]
catalyst [Rh {(R)-ntv} ] (2b; ntv = N-1,8-naphthoylvaline).
2
4
Substrates with allylic CÀH bonds were also studied to
enhance the scope of the reaction. The reaction still occurred
efficiently in 55–75% yield,but the diastereoselectivities
were moderate (38–50%,entries 12–14). These results,how-
ever,compare favorably with those described in previous
[
1g,12]
studies.
More interestingly,competitive rhodium-cata-
lyzed aziridination does not take place in the case of
Scheme 2. Structures of the S enantiomer of the sulfonimidamides 1
and of the rhodium catalysts 2. Ts=tosyl.
cyclohexene (13) and cyclopentene (14),contrary to previous
[23]
reports of the use of sulfonamides and sulfamates or of
[
13b]
rhodium acetate with sulfonimidamides.
This result is
likely to be the consequence of the matched effect which
favors CÀH insertion as the reaction of racemic 1a with the
chiral catalyst 2a affords a mixture of CÀH amination product
Thus,we decided to study the influence of other reaction
parameters. We were very surprised to observe that CÀH
amination with (S)-1a takes place in methanol,albeit in
13a and aziridine in the case of cyclohexene. Finally,the high
reactivity of the sulfonimidamide-derived nitrenes has been
confirmed by application of the procedure to simple alkanes
(entries 15 and 16). Adamantane 16 gives rise to the
corresponding CÀH insertion product 16a in 69% yield,
[
16]
moderate yields. A possible explanation is that methanol,
contrary to dichloromethane,allows the solubilization of 1a.
We also discovered that the reaction works equally well in the
absence of MgO. These observations prompted us to run the
reaction in mixtures of CH Cl and MeOH without a base. We
whereas the use of five equivalents of cyclohexane 17 affords
17a in 65% yield,which is identical to the highest yield
2
2
thus found that a 1:3 mixture of MeOH/CH Cl gives better
2
2
[
5h]
conversions; consequently,compound 4a could be isolated
starting from tetrahydronaphthalene in 48% yield. Further
obtained so far with cyclohexane as the solvent.
As both enantiomers of 1a are resolved with (S)- or (R)-a-
[
13a,b]
improvements were obtained by replacing CH Cl2 with
methylbenzylamine,
the absolute configuration at the
2
1
,1,2,2-tetrachloroethane and PhI(OAc) with the more
newly created asymmetric center for the CÀH insertion
product 5a,and by analogy for 3a–12a,was readily deter-
mined. Thus,the use of ( S)-1a with rhodium catalyst 2a leads
to the R configuration at the benzylic center. This result was
confirmed after removal of the sulfonimidoyl moiety from
ent-4a. The free amine 18,whose optical rotation corresponds
2
[
17]
soluble PhI(OCOtBu)2. The CÀH amination product 4a is
formed in 80% yield with 96% de (Table 1,entry 2) under
[
18]
these conditions and at À358C.
Application of this optimized procedure to electron-rich
CÀH bonds is particularly efficient (entries 1–6 and 8–11),
[
24]
whereas the reactivity drops slightly in the presence of an
electron-withdrawing group,as observed with p-nitroethyl-
benzene (8) (entry 7). Therefore,except in the latter case,this
stoichiometric intermolecular CÀH amination leads to the
to the S isomer,
was produced in 84% yield by using
sodium naphthanelide in THF at room temperature; whereas,
application of these conditions to 4a afforded (R)-18,as
indicated by the opposite optical rotation (Scheme 3). Impor-
tantly,chiral HPLC indicated that removal of the sulfonimi-
doyl group takes place without epimerization at the benzylic
center.
In conclusion,we have discovered a highly efficient
rhodium-catalyzed intermolecular CÀH amination procedure
with a sulfonimidamide as the nitrene precursor and the CÀH-
formation of a single product in 62–93% yield with nearly
[
19]
complete diastereoselectivity (ꢀ 93% de). These results,in
terms of reactivity and selectivity,are superior to those
reported so far,even in the presence of an excess of
[
1g,12]
substrate.
Moreover,with 2-methoxyindane ( 11),only
the trans isomer 11a was isolated in 62% yield with 99% de,
as indicated by NOESY experiments (entry 10). This result
illustrates the synthetic utility of the intermolecular CÀH
bond-containing substrate as the limiting component. This
reaction occurs with good-to-excellent diastereoselectivities
of up to 99%,particularly at secondary benzylic positions,
and can be applied with equal success to the synthesis of both
isomers of the resulting amine. The high reactivity and
selectivity have been shown to be the consequence of a
pronounced matched effect between the enantiomerically
pure sulfonimidamide and the chiral rhodium catalyst. Such a
procedure is of high interest for the total synthesis of natural
amination,as it stands in contrast to the intramolecular
[
5c–e,i]
version that affords only the corresponding cis isomer.
The high efficiency of this stereoselective CÀH function-
alization,which occurs with retention of configuration
[
5d,20]
through a concerted nitrene insertion,
dramatic matched effect between the chiral rhodium catalyst
a and the sulfonimidamide (S)-1a. On one hand,reaction of
is correlated to a
2
[
25]
the latter with [Rh (OAc) ] leads to very poor conversions
products,for example,colchicine
or biologically active
2
4
4
642 www.angewandte.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2006, 45, 4641 –4644

Angewandte
Chemie
[
a]
Table 1: Intermolecular CÀH amination with sulfonimidamide (S)-1a and catalyzed by [Rh {(S)-nttl} ] 2a.
2
4
[
b]
[c]
[b]
[c]
Entry
Substrate
Product
Yield [%]
de [%]
Entry
Substrate
Product
Yield [%]
de [%]
1
88
>99
9
62
99
2
3
80
96
10
11
62
78
99
98
[
d]
[d]
83
99
4
5
6
73
87
93
97
96
98
12
13
14
75
72
55
38
50
50
7
8
51
80
80
93
15
16
69
–
–
[
e]
65
[
a]All reactions were conducted at À358C in Cl CHCHCl /MeOH (3:1) with (S)-1a (1.2 equiv), PhI(OCOt-Bu) (1.4 equiv), and 2a (3 mol%). [b]Yield
2
2
2
of the isolated products. [c]The de values were determined by HPLC (Hypercarb or Symmetry Shield Column). [d] ent-4a was obtained using 3 mol%
of [Rh {(R)-ntv} ] (2b) and 1.2 equivalents of (R)-1a. [e]With 5.0 equivalents of cyclohexane.
2
4
[
26]
compounds,such as sertraline.
this area.
Studies are in progress in
Received: March 30,2006
Published online: June 21,2006
Keywords: amination · CÀH insertion · hypervalent iodine ·
.
nitrenes · rhodium
[
1] For recent reviews,see: a) C. Jia,T. Kitamura,Y. Fujiwara, Acc.
Chem. Res. 2001, 34,633 – 639; b) J. A. Labinger,J. E. Bercaw,
Nature 2002, 417,507 – 514; c) V. Ritleng,C. Sirlin,M. Pfeffer,
Chem. Rev. 2002, 102,1731 – 1769; d) F. Kakiuchi,N. Chatani,
Adv. Synth. Catal. 2003, 345,1077 – 1101; e) H. M. L. Davies,
Scheme 3. Deprotection of the CÀH insertion products under reductive
racemization-free conditions.
Angew. Chem. Int. Ed. 2006, 45, 4641 –4644
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 4643

Communications
R. E. J. Beckwith, Chem. Rev. 2003, 103,2861 – 2903; f) A. S.
Y. Yu,C.-M. Che, Angew. Chem. 2002, 114,3615 – 3618; Angew.
Chem. Int. Ed. 2002, 41,3465 – 3468; e) J. Zhang,P. W. Hong
Chan,C.-M. Che, Tetrahedron Lett. 2005, 46,5403 – 5408; f) C.
Fruit,P. Müller, Helv. Chim. Acta 2004, 87,1607 – 1615; g) C.
Fruit,P. Müller, Tetrahedron: Asymmetry 2004, 15,1019 – 1026.
[13] a) P. Di Chenna,F. Robert-Peillard,P. Dauban,R. H. Dodd,
Org. Lett. 2004, 6,4503 – 4505; b) C. Fruit,F. Robert-Peillard,G.
Bernardinelli,P. Müller,R. H. Dodd,P. Dauban, Tetrahedron:
Asymmetry 2005, 16,3484 – 3487; for a recently reported
analogous diastereoselective copper-catalyzed nitrene transfer,
see: c) D. Leca,A. Toussaint,C. Mareau,L. Fensterbank,E.
Lacôte,M. Malacria, Org. Lett. 2004, 6,3573 – 3575.
Goldman,K. I. Goldberg in Activation and Functionalization of
CÀH Bonds (Eds.: K. I. Goldberg,A. S. Goldman),ACS
Symposium Series 885,American Chemical Society,Washing-
ton,DC, 2004,pp. 1 – 43; g) A. R. Dick,M. S. Sanford, Tetrahe-
dron 2006, 62,2439 – 2463.
[
[
2] For recent examples,see: a) F. Kakiuchi,S. Kan,K. Igi,N.
Chatani,S. Murai, J. Am. Chem. Soc. 2003, 125,1698 – 1699;
b) O. Baudoin,A. Herrbach,F. GuØritte, Angew. Chem. 2003,
1
15,5914 – 5918; Angew. Chem. Int. Ed. 2003, 42,5736 – 5740;
c) R. K. Thalji,J. A. Ellman,R. G. Bergman, J. Am. Chem. Soc.
004, 126,7192 – 7193; d) D. Kalyani,N. R. Deprez,L. V. Desai,
2
M. S. Sanford, J. Am. Chem. Soc. 2005, 127,7330 – 7331.
3] For recent examples,see: a) S. Lee,P. L. Fuchs, J. Am. Chem.
Soc. 2002, 124,13978 – 13979; b) L. V. Desai,K. L. Hull,M. S.
Sanford, J. Am. Chem. Soc. 2004, 126,9542 – 9543; c) R. Giri,J.
Liang,J.-G. Lei,J.-J. Li,D.-H. Wang,X. Chen,I. C. Naggar,C.
Guo,B. M. Foxman,J.-Q. Yu, Angew. Chem. 2005, 117,7586 –
[14] For previous preparations of sulfonimidamides,see: a) E. S.
Levchenko,N. Y. Derkach,A. V. Kirsanov, Zh. Obshch. Khim.
1962, 32,1208 – 1212; b) S. Tsushima,Y. Yamada,T. Onami,K.
Oshima,M. O. Chaney,N. D. Jones,J. K. Swartzendruber, Bull.
Chem. Soc. Jpn. 1989, 62,1167 – 1178.
[
[
15] P. Müller,Y. Allenbach,E. Robert, Tetrahedron: Asymmetry
2003, 14,779 – 785.
7590; Angew. Chem. Int. Ed. 2005, 44,7420 – 7424; d) B. H.
16] This result is unexpected as it has been shown that protic
solvents induce hydrolysis of the (presumably formed) imino-
iodane in the presence of transition-metal complexes; see:
a) R. E. White, Inorg. Chem. 1987, 26,3916 – 3919; b) D. A.
Evans,M. M. Faul,M. T. Bilodeau, J. Am. Chem. Soc. 1994, 116,
Brodsky,J. Du Bois, J. Am. Chem. Soc. 2005, 127,15391 – 15393.
4] For recent examples,see: a) J. L. Brice,J. E. Harang,V. I.
Timokhin,N. R. Anastasi,S. S. Stahl, J. Am. Chem. Soc. 2005,
[
127,2868 – 2869; b) W. C. P. Tsang,N. Zheng,S. L. Buchwald, J.
Am. Chem. Soc. 2005, 127,14560 – 14561; c) H. Lebel,K. Huard,
S. Lectard, J. Am. Chem. Soc. 2005, 127,14198 – 14199; d) T.
Katsuki, Chem. Lett. 2005, 34,1304 – 1309.
2742 – 2753.
[
[
17] J. Du Bois, Chemtracts: Org. Chem. 2005, 18,1 – 13.
18] Under these conditions,the sulfonimidamide ( S)-1b is less
soluble than 1a,thus leading to lower yields.
[
5] For the most relevant examples using iminoiodanes,see: a) X.-
Q. Yu,J.-S. Huang,X.-G. Zhou,C.-M. Che, Org. Lett. 2000, 2,
[
19] It is also worth mentioning that no competitive sulfimidation
takes place with 2-ethylthiophene (entry 11). T. Otani,Y.
2233 – 2236; b) S.-M. Au,J.-S. Huang,C.-M. Che,W.-Y. Yu,
J.
Org. Chem. 2000, 65,7858 – 7864; c) J.-L. Liang,S.-X. Yuan,J.-S.
Sugihara,A. Ishii,J. Nakayama,
549 – 5552.
Tetrahedron Lett. 1999, 40,
Huang,C.-M. Che, J. Org. Chem. 2004, 69,3610 – 3619; d) C. G.
Espino,J. Du Bois, Angew. Chem. 2001, 113,618 – 620; Angew.
Chem. Int. Ed. 2001, 40,598 – 600; e) C. G. Espino,P. M. Wehn,J.
Chow,J. Du Bois, J. Am. Chem. Soc. 2001, 123,6935 – 6936;
f) P. M. Wehn,J. Lee,J. Du Bois, Org. Lett. 2003, 5,4823 – 4826;
5
[
[
[
[
20] I. Nꢁgeli,C. Baud,G. Bernardinelli,Y. Jacquier,M. Moran,P.
Müller, Helv. Chim. Acta 1997, 80,1087 – 1105.
21] This result strongly suggests a kinetic resolution of 1a,the scope
and application of which are currently under investigation.
22] P. Müller,G. Bernardinelli,Y. Allenbach,M. Ferri,H. D. Flack,
Org. Lett. 2004, 6,1725 – 1728.
g) M. Kim,J. V. Mulcahy,C. G. Espino,J. Du Bois,
006, 8,1073 – 1076; h) M. M. Diaz-Requejo,T. R. Belderrain,
M. C. Nicasio,S. Trofimenko,P. J. Perez, J. Am. Chem. Soc. 2003,
Org. Lett.
2
23] a) K. Guthikonda,J. Du Bois, J. Am. Chem. Soc. 2002, 124,
125,12078 – 12079; i) Y. Cui,C. He, Angew. Chem. 2004, 116,
13672 – 13673; b) P. Müller,C. Baud,Y. Jacquier,M. Moran,I.
4306 – 4308; Angew. Chem. Int. Ed. 2004, 43,4210 – 4212.
Nꢁgeli, J. Phys. Org. Chem. 1996, 9,341 – 347.
[
6] a) J. A. Johnson,N. Li,D. Sames, J. Am. Chem. Soc. 2002, 124,
[
[
[
24] O. Cervinka,V. Dudek, Collect. Czech. Chem. Commun. 1973,
6900 – 6903; b) A. Hinman,J. Du Bois, J. Am. Chem. Soc. 2003,
3
8,1159 – 1164.
25] T. Graening,H.-G. Schmalz, Angew. Chem. 2004, 116,3292 –
3318; Angew. Chem. Int. Ed. 2004, 43,3230 – 3256.
26] G. J. Quallich, Chirality 2005, 17,3230 – 3256.
125,11510 – 11511; c) S. J. OꢀMalley,K. L. Tan,A. Watzke,R. G.
Bergman,J. A. Ellman, J. Am. Chem. Soc. 2005, 127,13496 –
3497.
7] For general reviews,see: a) P. Müller,C. Fruit, Chem. Rev. 2003,
3
1
[
103,2905 – 2919; b) P. Dauban,R. H. Dodd, Synlett 2003,1571 –
1586; c) J. A. Halfen, Curr. Org. Chem. 2005, 9,657 – 669;
d) C. G. Espino,J. Du Bois in Modern Rhodium-Catalyzed
Organic Reactions (Ed.: P. A. Evans),Wiley-VCH,Weinheim,
2
005,pp. 379 – 416; e) H. M. L. Davies,M. S. Long,
Chem. 2005, 117,3584 – 3586; Angew. Chem. Int. Ed. 2005, 44,
518 – 3520.
8] a) R. Breslow,S. H. Gellman, J. Chem. Soc. Chem. Commun.
Angew.
3
[
[
1
1
982,1400; b) R. Breslow,S. H. Gellman, J. Am. Chem. Soc.
983, 105,6728 – 6729.
9] D. Mansuy,J.-P. Mahy,A. Dureault,G. Bedi,P. Battioni,
J.
Chem. Soc. Chem. Commun. 1984,1161 – 1162.
[
[
[
10] P. Dauban,L. Sani›re,A. Tarrade,R. H. Dodd, J. Am. Chem.
Soc. 2001, 123,7707 – 7708.
11] C. G. Espino,K. W. Fiori,M. Kim,J. Du Bois, J. Am. Chem. Soc.
2
004, 126,15378 – 15379.
12] a) Y. Kohmura,T. Katsuki, Tetrahedron Lett. 2001, 42,3339 –
342; b) M. Yamawaki,H. Tsutsui,S. Kitagaki,M. Anada,S.
Hashimoto, Tetrahedron Lett. 2002, 43,9561 – 9564; c) J.-L.
Liang,J.-S. Huang,X.-Q. Yu,N. Zhu,C.-M. Che, Chem. Eur. J.
002, 8,1563 – 1572; d) J.-L. Liang,S.-X. Yuan,J.-S. Huang,W.-
3
2
4
644 www.angewandte.org
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