Chiral magnesium bis(sulfonamide) complexes as catalysts for the merged enolization and enantioselective amination of N-acyloxazolidinones. A catalytic approach to the synthesis of arylglycines [6]

Full text of DOI:10.1021/ja971367f

6452
J. Am. Chem. Soc. 1997, 119, 6452-6453
Chiral Magnesium Bis(sulfonamide) Complexes as
Catalysts for the Merged Enolization and
Enantioselective Amination of N-Acyloxazolidinones.
A Catalytic Approach to the Synthesis of
Arylglycines
bases such as La(Ot-Bu)3 or NaOt-Bu also catalyze the
amination of imide 1 to afford the hydrazide 2a in g95:5 [2(S):
2
(R)] diastereoselectivity (eq 2). In an attempt to identify the
David A. Evans* and Scott G. Nelson1
Department of Chemistry and Chemical Biology
HarVard UniVersity, Cambridge, Massachusetts 02138
ReceiVed April 30, 1997
There is considerable interest in the development of catalyzed
enantioselective enolate-electrophile bond constructions to
complement existing procedures which typically employ sto-
ichiometric chiral controllers. In the design of these catalytic
processes it would be highly desirable to merge the enolization
event with the desired enantioselective bond construction.
participating base in the catalytic cycle, the competency of the
hydrazide conjugate base 2b in promoting enolization was
investigated. Indeed, 5 mol % of the sodium anion 2b catalyzed
the electrophilic amination of 1 with diastereoselectivity identical
to that obtained under NaOt-Bu catalysis, indicating that the
metal alkoxide is probably serving simply as an initiator, while
the hydrazide conjugate base functions as the base in the
catalytic cycle. This observation strongly suggests that hy-
2
Catalyzed â-ketoester conjugate additions, isocyanoacetic ester
3
4
aldol reactions, and nitro aldol reactions are among the few
examples that meet this design criterion. The purpose of this
Communication is to disclose a chiral metal complex that will
mediate the enolization and enantioselective electrophilic ami-
nation (El(+) ) BocNdNBoc) of aryl-substituted carboximides
(
eq 1) that possess a considerably lower predisposition toward
8
enolization than the substrates employed in those studies cited
above.
drazide anions (pKa DMSO ≈ 17-18) are effective bases for
2
-4
the enolization of carboximides such as 1.
Enantioselective Catalysis. The preceding observations
suggested that sulfonamide-derived bases should be sufficiently
basic to effect substrate enolization. Accordingly, we were
attracted to metallo-bis(sulfonamide) complexes derived from
chiral diamines as potential chiral catalysts. In conjunction with
the optimization process, diamine, metal, and sulfonamide
moieties were systematically screened to maximize turnover
rates and enantioselection. The most successful of this family
of promoters was generated by treating (S,S)-bis(sulfonamide)
Catalyzed Enolization. Aryl-substituted carboximides were
selected for the development of these processes with the
expectation that they would be moderately activated toward
enolization and would afford structurally well-defined enolate
9
10
3
with dimethylmagnesium in dichloromethane to provide
5
complexes. Azodicarboxylate esters (El(+) ) RO2CNdNCO2R)
11,12
the magnesium bis(sulfonamide) complex 4 (eq 3).
The
were chosen as the electrophilic reaction component to provide
a vehicle for evaluating catalyst-enolate structure and catalyst
turnover.6 We have previously demonstrated that oxazolidi-
none imide enolates generated using prototypical stoichiometric
conditions (1.0 equiv of LDA) undergo stereoselective electro-
philic amination using di-tert-butyl azodicarboxylate as the
catalyzed amination of phenylacetylimide 5a, employing mag-
,7
6
c,e
electrophilic nitrogen source [2(S):2(R) ) 97:3] (eq 2).
As
a precondition for the catalyzed reaction variant, we first
demonstrated that substoichiometric quantities (5 mol %) of
(
1) (a) NIH Postdoctoral Fellow 1992-1994. (b) Present address:
University of Pittsburgh, Department of Chemistry, Pittsburgh, PA 15260.
(
2) (a) Feringa, B. l.; de Vries, A. H. M. AdVances in Catalytic Processes;
JAI Press: London, 1995; pp 151-192 and references cited therein. (b)
Sasai, H.; Arai, T.; Satow, Y.; Houk, K. N.; Shibasaki, M. J. Am. Chem.
Soc. 1995, 117, 6194-6198.
nesium complex 4 (10 mol %) and N-methyl-p-toluenesulfon-
amide (20 mol %) in 2:1 CH2Cl2/Et2O, afforded the hydrazide
(
3) Ito, Y.; Sawamura, M.; Hayashi, T. J. Am. Chem. Soc. 1986, 108,
6
a with an enantiomeric ratio of 2(S):2(R) ) 93:7 in 92% yield
6
405-6406.
4) (a) Sasai, H.; Suzuki, T.; Arai, S.; Arai, T.; Shibasaki, M. J. Am.
Chem. Soc. 1992, 114, 4418-4420. (b) Reference 2b, footnote 2.
5) Alkali metal enolates of oxazolidinone-derived imides exhibit a strong
(eq 4). This amination procedure is applicable to a variety of
(
aryl-substituted imides (Table 1); substrates incorporating either
(
proclivity for adopting chelated (Z) enolate structures, see: (a) Evans, D.
A. Aldrichimica Acta 1982, 15, 23-32. (b) Evans, D. A.; Britton, T. C.;
Ellman, J. A.; Dorow, R. L. J. Am. Chem. Soc. 1990, 112, 4011-4030. (c)
Evans, D. A.; Rieger, D. L.; Bilodeau, M. T.; Urpi, F. J. Am. Chem. Soc.
(8) This value is an estimate of the pKa of the hydrazide in DMSO derived
from values reported for related functional groups, see: Bordwell, F. G.
Acc. Chem. Res. 1988, 21, 456-463.
(9) Bis(sulfonamide) 3 was prepared by treating (1S,2S)-diphenylethyl-
enediamine with 2,5-dimethylbenzenesulfonyl chloride; see Supporting
Information for full procedural details.
1
991, 113, 1047-1049.
(
6) For the electrophilic amination of enolates using azodicarboxylate
esters, see: (a) Gennari, C.; Colombo, L.; Bertolini, G. J. Am. Chem. Soc.
(10) The dimethylmagnesium employed in this study was prepared as
an ∼0.5 M solution in diethyl ether, see: Ashby, E. C.; Arnott, R. J.
Organomet. Chem. 1968, 14, 1-11.
1
986, 108, 6394-6395. (b) Oppolzer, W.; Moretti, R. HelV. Chim. Acta.
1
986, 69, 1923-1926. (c) Evans, D. A.; Britton, T. C.; Dorow, R. L.;
Dellaria, Jr., J. F. J. Am. Chem. Soc. 1986, 108, 6395-6397. (d) Trimble,
L. A.; Vederas, J, C. J. Am. Chem. Soc. 1986, 108, 6397-6399. (e) Evans,
D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J. F., Jr. Tetrahedron 1988,
(11) Structure 4 is provided to represent metal-ligand stoichiometry.
1
Catalyst aggregation, alluded to by H NMR spectroscopy, may affect the
exact nature of the catalytic species.
4
4, 5525-5540.
(
(12) Catalyst architecture, specifically the structure of the diamine
backbone and of the sulfonamide aryl moiety, dramatically influences the
catalytic competency of the derived magnesium complex. The catalyst
complex optimized for each of these variables is reported herein.
7) Vederas has recently reported the diastereoselective amination of
enolates using chiral azodicarboxylate reagents: Harris, J. M.; McDonald,
R.; Vederas, J. C. J. Chem. Soc., Perkin Trans. 1 1995, 2669-2674.
S0002-7863(97)01367-X CCC: $14.00 © 1997 American Chemical Society

Communications to the Editor
J. Am. Chem. Soc., Vol. 119, No. 27, 1997 6453
Table 1. Enantioselective Amination of N-Acyloxazolidinones 5a,b
Figure 1. Chiral magnesium bis(sulfonamide)-enolate complex.
Our analysis leads us to conclude that catalyst turnover, rather
than enolization, is the rate-determining step in this reaction
and that the observed first order dependence on N-methyl-p-
toluenesulfonamide results from an accelerated rate of hydrazide
conjugate protonation and the associated liberation of the active
catalyst.
a
Reactions were carried out using the conditions given in ref 14 at
b
The sense of asymmetric induction in the preceding reactions
can be rationalized by assuming that the reaction proceeds via
the intermediacy of the chelated tetrahedral magnesium enolate
the indicated times and temperatures. Absolute configuration of
adducts 6 were assigned by the procedure outlined in ref 13. c Enan-
tiomeric purity was determined by chiral HPLC assay (Daicel Chiralcel
OD-H). Values reported are those for chromatographically purified
hydrazides. Values reported are those for recrystallized hydrazides.
d
15
complex depicted in Figure 1. Important structural attributes
e
of this complex include the (Z) enolate geometry and the
conformational rigidity enforced by chelation of both the imide
enolate and bis(sulfonamide) ligand to the tetrahedral magne-
sium ion. Our studies on chiral oxazolidinone-derived imide
enolate mediated bond constructions that uniformly proceed
through analogous structures with chelating metals (Li, Na, Mg,
Ti), provide circumstantial support for this assumption.5 Gear-
ing between the aryl groups resident within the diamine
backbone and the arylsulfonamide residues forces one aromatic
ring to project over the enolate π-system, exposing the (Si)
enolate R carbon diastereoface to the incoming electrophile.1
The present study establishes that lanthanide and alkali metal
alkoxides as well as magnesium-bis(sulfonamide) complexes
are effective catalysts for executing enantioselective enolate
amination in simple carboxylate ester synthons. Extension of
these concepts to a general catalytic enantioselective approach
to the synthesis of R-amino acids as well as other enolate-
electrophile bond constructions is the subject of ongoing
investigations.
electron-withdrawing (entry b) or electron-donating substituents
(
entry c) as well as disubstituted aryl substituents (entries d-f)
afford relatively high enantiomeric ratios [2(S):2(R) ) 95:5 to
9
1
3
0:10]. The amination adducts 6a-f illustrated in Table 1
are all highly crystalline. In each instance, a single recrystal-
lization of the product hydrazides leads to enantiomer enrich-
ment (96 f 99% ee).14 Finally, the potential for utilizing lower
catalyst loadings was demonstrated by the preparation of
hydrazide 6c from imide 5c in >99% ee and 81% yield after
recrystallization using 5 mol % of 4 and 10 mol % N-methyl-
p-toluenesulfonamide.
The role of N-methyl-p-toluenesulfonamide in this catalytic
process has not yet been completely elucidated; however, this
addend clearly accelerates the reaction. A kinetic investigation
reveals a first-order dependence of this addend on reaction rate.
6
(
13) The absolute configuration of the R-hydrazido imides 6 (Table 1)
were established by conversion to the corresponding R-hydrazido carboxylic
acids and correlation of their optical rotation to those of authentic samples
of known configuration. See ref 6d.
Acknowledgment. We gratefully acknowledge the NIH, the NSF,
and Merck for research support. The NIH BRS Shared Instrumentation
Grant Program 1-S10-RR04870 and the NSF (CHE 88-14019) are
acknowledged for providing NMR facilities.
(14) Typical experimental procedure: Under an inert atmosphere (Ar
or N2), 15 mg (25 µmol) of bis(sulfonamide) 3 in 0.5 mL of CH2Cl2 is
treated with 1.0 equiv (25 µmol) of dimethylmagnesium at ambient
temperature. After stirring 1 h, the turbid catalyst solution is cooled to -78
Supporting Information Available: Experimental procedures and
enantiomeric purity assays for all compounds are provided (6 pages).
See any current masthead page for ordering and Internet access
instructions.
°
C and a solution of 0.25 mmol of imide 5, 69 mg (1.2 equiv, 0.30 mmol)
of di-tert-butylazodicarboxylate, and 9.4 mg (50 µmol) of N-methyl-p-
toluenesulfonamide in 1 mL of 1:1 CH2Cl2/Et2O is added via cannula. The
reaction mixture is then warmed to -65 °C and stirred 48-72 h. The
reaction is quenched at -65 °C by the addition of glacial acetic acid (200
µL), and the reaction mixture is then poured into a saturated aqueous sodium
bicarbonate solution. The crude product is isolated by extraction with
dichloromethane and concentration of the organic extracts in Vacuo.
Purification of the product mixture by flash chromatography affords the
desired hydrazide 6 with the indicated yield and enantioselectivity, along
with recovered bis(sulfonamide) 3. The enantiomeric excess of the isolated
hydrazide 6 is g96% after a single recrystallization (ethyl acetate-hexane).
JA971367F
(15) The magnesium enolate complex depicted in Figure 1 was minimized
using the Spartan Modeling Package (Version 4.0). Geometry optimizations
were performed using the PM3 parameter set.
(16) For a discussion of “gearing” in related bis(sulfonamide) ligands,
see: Corey, E. J.; Imwinkelried, R.; Pikul, S.; Xiang, Y. B. J. Am. Chem.
Soc. 1989, 111, 5493-5495.