Communications
bearing more bulky acyl substituents were also investigated.
The reaction between methyl a-keto butyrate (5d) and 4 gave
d with 89% ee at room temperature (Table 2, entry 4).No
by flash chromatography.For analytical data and determinations of
the ee values see the Supporting Information.
6
Received: June 14, 2004
conversion was observed at lower temperatures.The sterically
more-demanding ethyl 2-oxo-4-phenyl butyrate (5e) yielded
Keywords: aldol reaction · asymmetric catalysis · copper ·
N ligands · sulfoximines
6
e with 96% ee at À208C (Table 2, entry 5).Apparently, the
.
catalyst tolerates an enlarged alkyl chain adjacent to the acyl
function, although in some cases higher temperatures are
required.
[
[
1] J.K.Whitehead, H.R.Bentley, J. Chem. Soc. 1952, 1572 – 1574.
2] Reviews: a) C.R.Johnson, Acc. Chem. Res. 1973, 6, 341 – 347;
b) S.G.Pyne, Sulfur Rep. 1992, 12, 57 – 59; c) M.Reggelin, C.
Zur, Synthesis 2000, 1 – 64.
To test the applicability of another enolsilane, benzyl
pyruvate (5b) was treated with 1-methyl-1-(trimethylsilyl-
oxy)ethane (11) to afford the corresponding product 6 f with
9
1% ee in 71% yield (Scheme 3).
[3] Selected reviews: a) A.Meister, Biochim. Biophys. Acta 1995,
1271, 35 – 42; b) M.E. Anderson, Chem.-Biol. Interact. 1998,
11, 1 – 14; h) L.L. Muldoon, L.S.L. Walker-Rosenfeld, C.
1
Hale, S.E.Purcell, L.C.Bennett, E.A.Neuwelt,
J. Pharmacol.
Exp. Ther. 2001, 296, 797 – 805.
[
4] a) W.L.Mock, J .- T.Tsay, J. Am. Chem. Soc. 1989, 111, 4467 –
4
6
1
472; b) W.L.Mock, J.Z.Zhang, J. Biol. Chem. 1991, 266, 6393 –
400; c) C.Bolm, G.Moll, J.D.Kahmann, Chem. Eur. J. 2001, 7,
118 – 1128; d) C.Bolm, D.Müller, C.P.R.Hackenberger,
Org.
Scheme 3. Synthesis of 6 f. Tf=trifluoromethanesulfanyl.
Lett. 2002, 4, 893 – 896; e) C.Bolm, D.Müller, C.Dalhoff,
C.P.R.Hackenberger, E.Weinhold, Bioorg. Med. Chem. Lett.
2
003, 13, 3207 – 3211.
In summary, we have described the synthesis of new C1-
symmetric benzene-bridged aminosulfoximines, which are
capable of serving as efficient ligands in copper-catalyzed
enantioselective Mukaiyama-type aldol reactions.Aldol
products with quarternary centers, which are commonly
[
5] For selected contibutions, see: a) M.Reggelin, T.Heinrich,
Angew. Chem. 1998, 110, 3005 – 3008; Angew. Chem. Int. Ed.
1998, 37, 2883 – 2886; ; b) M.Harmata, X.Hong, C.L.Barnes,
Tetrahedron Lett. 2003, 44, 7261 – 7264; c) S.Koep, H .- J.Gais, G.
Raabe, J. Am. Chem. Soc. 2003, 125, 9653 – 9667.
[6] Reviews: a) M.Harmata, Chemtracts 2003, 16, 660 – 666; b) H.
Okamura, C.Bolm, Chem. Lett. 2004, 33, 482 – 487, and
references therein.
[
17]
difficult to prepare in enantiomerically enriched form,
have been obtained with up to 99% ee in high yields.In
terms of ee values and yield, the new catalysts compare well
[
7] For Pd-catalyzed allylic alkylations, see: a) C.Bolm, O.Simic, M.
Martin, Synlett 2001, 12, 1878 – 1880; b) M.Harmata, S K. .
Ghosh, Org. Lett. 2001, 3, 3321 – 3323.
2
+
2+
with the established [Cu(tBubox)] or [Sn(pybox)] sys-
tems.
[
10,18]
Ongoing studies are directed to further expand the
substrate scope and to demonstrate the applicability of the
novel aminosulfoximines in other enantioselective catalyses.
[8] For Cu-catalyzed cycloadditions reactions, see: a) C.Bolm, O.
Simic, J. Am. Chem. Soc. 2001, 123, 3830 – 3831; b) C.Bolm, M.
Martin, O.Simic, M.Verrucci, Org. Lett. 2003, 5, 427 – 429; c) C.
Bolm, M.Verrucci, O.Simic, P.G.Cozzi, G.Raabe, H.Okamura,
Chem. Commun. 2003, 2826 – 2827.
Experimental Section
[9] C.Bolm, M.Martin, G.Gescheidt, C.Palivan, D.Neshchadin, H.
Representative example for the syntheses of aminosulfoximines 3a–
e: Preparation of 3e: Glacial acetic acid (172 mL, 3.00 mmol) was
added to a solution of aniline 10 (3.00 mmol, 739 mg) and 2,4,6-
triisopropylbenzaldehyde (3.60 mmol, 837 mg) in MeOH (20 mL) at
RT.The solution was stirred for 3 h and then cooled to 0 8C.
Bertagnolli, M.P.Feth, A.Schweiger, G.Mitrikas, J.Harmer,
Am. Chem. Soc. 2003, 125, 6222 – 6227.
[10] For examples of highly enantioselective addition reactions of
enolsilyl ethers and pyruvate esters or glyoxalates, see: a) K.
Mikami, S.Matsukawa, J. Am. Chem. Soc. 1994, 116, 4077 –
J.
Subsequently, NaBH (7.50 mmol, 284 mg) was added over 20 min,
4078; b) D.A. Evans, J.A. Murry, M.C. Kozlowski,
Chem. Soc. 1996, 118, 5814 – 5815; c) D.A. Evans, M.C.
Kozlowski, C.S. Burgey, D.W.C. MacMillan, J. Am. Chem.
J. Am.
4
and the mixture was stirred at RT overnight.The solution was
partitioned between 10% aqueous K CO3 (20 mL) and CH Cl
2
2
2
(
2
20 mL), and the aqueous layer was extracted with CH Cl (3
Soc. 1997, 119, 7893 – 7894; d) D.A.Evans, D.W.C.MacMillan,
K.R. Campos, J. Am. Chem. Soc. 1997, 119, 10859 – 10860;
e) D.A.Evans, M.C.Kozlowski, J.A.Murry, C.S.Burgey, K.R.
Campos, B.T.Connel, R.J.Staples, J. Am. Chem. Soc. 1999, 121,
669 – 685; f) D.A. Evans, C.S. Burgey, M.C. Kozlowski, S.W.
Tregay, J. Am. Chem. Soc. 1999, 121, 686 – 699; g) D.A.Evans,
C.E.Masse, J.Wu, Org. Lett. 2002, 4, 3375 – 3378.
2
2
0 mL).The combined organic layers were dried over MgSO , and
4
the solvent was evaporated.The product was purified by flash
chromatography on silica gel (pentane/EtOAc 10:1) to afford 1.14 g
(
2.46 mmol, 82%) of 3e as a colorless solid.For analytical data see the
Supporting Information.
General procedure for the Mukaiyama-type aldol reaction: A
flame-dried Schlenk flask under Ar atmosphere was charged with
Cu(OTf)2 (18.1 mg, 0.05 mmol) and the aminosulfoximine 3a–e
[11] For example, copper(ii) complexes of 1a and 1b gave 6a with
only 35 and 58% ee, respectively.For the results obtained with
metal complexes bearing N-quinolyl-substituted sulfoximine 2,
see: M.Verrucci, dissertation RWTH Aachen, 2004.
(
0.05 mmol). Dry THF (2 mL) was then added and the resulting
deep green solution was stirred for 30 min at RT.The mixture was
subsequently cooled to the selected temperature, and the a-keto ester
[12] a) R.Fusco, F.Tericoni, Chem. Ind. (Milan) 1965, 47, 61 – 62;
b) C.R.Johnson, C.W.Schroeck, J. Am. Chem. Soc. 1973, 95,
5
a–e (0.5 mmol), silylenol ether 4 (0.6 mmol, 123 mL), and 2,2,2-
trifluoroethanol (0.6 mmol, 44 mL) were added.After stirring the
reaction mixture for the indicated period of time, it was warmed to
RT, diluted with diethyl ether (50 mL) and filtered through a plug of
silica gel.The solvent was evaporated, and the product was purified
7418 – 7423; c) J.Brandt, H .J .Gais,
1997, 8, 909 – 912.
[13] a) C.Bolm, J.P.Hildebrand, Tetrahedron Lett. 1998, 39, 5731 –
5734; b) C.Bolm, J.P.Hildebrand, J. Org. Chem. 2000, 65, 169 –
Tetrahedron: Asymmetry
5
986
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2004, 43, 5984 –5987