C2-Symmetric Tin(II) complexes as chiral Lewis acids, catalytic enantioselective anti aldol additions of enolsilanes to glyoxylate and pyruvate esters

Full text of DOI:10.1021/ja972547s

J. Am. Chem. Soc. 1997, 119, 10859-10860
10859
Table 1. Enantioselective Aldol Reactions between Ethyl
Glyoxylate and Representative Silylketene Acetals (Eq 2)
C2-Symmetric Tin(II) Complexes as Chiral Lewis
Acids. Catalytic Enantioselective Anti Aldol
Additions of Enolsilanes to Glyoxylate and Pyruvate
Esters
David A. Evans,* David W. C. MacMillan, and
Kevin R. Campos
Department of Chemistry and Chemical Biology
HarVard UniVersity, Cambridge, Massachusetts 02138
ReceiVed July 28, 1997
a Product ratios determined by HPLC using a Chiralcel OD-H or
AD column after hydrolysis of the product TMS ether (ref 10).
b Relative and absolute stereochemical assignments determined by
independent synthesis (see Supporting Information). c Enolsilane ge-
ometry (Z), isomeric purity g95%. d Product configuration assigned
by analogy. e This experiment was carried out with catalyst 1b (10 mol
%).
Stannous triflate-diamine complexes are effective organi-
zational centers for Lewis acid promoted aldol reactions.1
However, the documented difficulties in rendering these pro-
cesses catalytic in metal complex appear to contradict the
established fact that Sn(II) complexes are kinetically labile
toward ligand substitution.2 In this communication we dem-
onstrate that ligand architecture can play an important role in
the design of Sn(II)-based chiral Lewis acidic complexes.
Specifically, the Lewis acidic complexes 1 and 2 derived from
Sn(OTf)23 and bidentate bis(oxazoline)4 and tridentate pyridyl-
bis(oxazoline)5 ligands6 are efficient anti-aldol catalysts for the
enantioselective addition of enolsilanes to 1,2-dicarbonyl com-
pounds. These ligand-metal complexes exhibit efficient turn-
over in the catalytic cycle and may be employed in amounts as
low as 2 mol %.
superior levels of asymmetric induction exhibited by [Sn((S,S)-
Bn-box)](OTf)2 (1a) which afforded (S)-4 in 98% ee (10 mol
% catalyst, CH2Cl2, -78 °C, 5 min, 99% yield) prompted us to
select this catalyst for further exploration.10 The addition of
substituted (Z) silylketene acetal11 5 to ethyl glyoxylate (eq 1,
R ) Me) in the presence of 1a provides the malate derivative
(S)-612 in high enantioselectivity (95% ee), yield (87%), and
anti reaction diastereoselection (90:10 anti:syn). To our knowl-
edge, only one previous example of a chiral Lewis acid catalyzed
anti-aldol reaction has been reported,13 albeit with higher catalyst
loadings and lower enantioselectivities. As such, further study
into the generality of [Sn((S,S)-Bn-box)](OTf)2 as an anti aldol
catalyst was undertaken (Table 1).
From the results summarized in Table 1, both anti diaste-
reoselection and reaction enantioselectivity (95-98% ee) are
maintained for a range of alkyl-substituted silylketene acetals
(entries 2-5, Me, Et, iPr, iBu). These data document a modest
trend toward higher anti diastereoselection as the steric require-
ments of the enolsilane alkyl substituent increase. Although
phenyl thioester-derived silylketene acetals are generally superior
for additions to glyoxylate esters mediated by 1a, substituted
enolsilanes derived from ethyl and tert-butyl thioesters can also
furnish anti-aldol adducts in high enantioselectivity (entries 6
and 7) (g92:8 anti:syn, 92-96% ee) in the presence of [Sn-
((S,S)-iPr-box)](OTf)2 (1b). The preparative utility of this
methodology has also been evaluated. The addition of si-
lylketene acetal 3 to ethyl glyoxylate was performed on a 25-
mmol scale utilizing complex 1a (2 mol %) to afford (S)-4 (94%
ee, 90% yield).14
The efficiency of complexes 1 and 2 in catalyzing the addition
of enolsilanes to glyoxylate esters (eq 1) was examined.7 In
analogy to related Cu(II) studies,8 it was assumed that chelate
organization between the catalyst and carbonyl-containing
reactant might provide a stereoselective process with this and
related substrates. A survey of ligand architecture for the
addition of silylketene acetal 3 to ethyl glyoxylate (eq 1, R )
H) revealed that several [Sn(box)](OTf)2 complexes 1 (10 mol
%, -78 °C, 5 min) efficiently catalyze the formation of the
malate diester 4 in good yield in greater than 90% ee.9 The
(1) (a) Kobayashi, S.; Horibe, M.; Saito, Y. Tetrahedron 1994, 50, 9629-
42. (b) Kobayashi, S.; Uchiro, H.; Shiina, I.; Mukaiyama, T. Tetrahedron
1993, 49, 1761-72.
The capacity of complexes 1 and 2 to facilitate catalyst-
substrate organization through presumed bidentate coordination
was further evaluated with R-keto esters.15 Ligand optimization
in the addition of the substituted silylketene acetal 7 to methyl
pyruvate indicated that both Sn(II)-box and -pybox complexes
(2) Veith, M.; Recktenwald, O. Topics in Current Chemistry, Organotin
Compounds; Springer: Berlin, 1982; Vol. 104, pp 1-58.
(3) Batchelor, R. J.; Ruddick, J. N. K.; Sams, J. R.; Auble, F. Inorg.
Chem. 1977, 16, 1414-17.
(4) Evans, D. A.; Woerpel, K. A.; Hinman, M. M.; Faul, M. M. J. Am.
Chem. Soc. 1991, 113, 726-8.
(10) The catalysts were prepared as described above, see ref 7. In a
representative procedure the silylketene acetal (0.50 mmol) and ethyl
glyoxylate (0.75 mmol) were added sequentially to a catalyst solution in
CH2Cl2 (0.8 mL, 0.05 mmol, 10 mol %) at -78 °C. After the reaction was
complete (5 min-2 h), the mixture was filtered through silica with Et2O,
and the silyl ether was hydrolyzed with 1 N HCl in THF (30 min, 25 °C)
to yield the hydroxyester, which was purified by flash chromatography.
(11) For the addition to ethyl glyoxylate catalyzed by 1 and 2,
(E)-silylketene acetals were found to be less reactive and led to the formation
of malate derivatives in lower yield and with diminished anti selectivity.
(12) 3-Alkyl malic acid derivatives may also be obtained through
alkylation of the malate diester-derived enolate. Seebach, D.; Aebi, J.;
Wasmuth, D. Org. Synth. 1984, 63, 109-120, and references cited therein.
(13) Parmee, E. R.; Hong, Y.; Tempkin, O.; Masamune, S. Tetrahedron
Lett. 1992, 33, 1729-32.
(5) Nishiyama, H.; Kondo, M.; Nakamura, T.; Itoh, K. Organometallics
1991, 10, 500-8.
(6) Sn(OTf)2 derived bis(oxazoline) and pyridyl-bis(oxazoline) complexes
are denoted as [Sn(box)](OTf)2 and [Sn(pybox)](OTf)2, respectively.
(7) Typically the catalysts were formed by stirring bis(oxazolinyl) (0.055
mmol) or bis(oxazolinyl)pyridyl ligands (0.055 mmol) with Sn(OTf)2 (0.05
mmol) in CH2Cl2 (0.8 mL) for 1 h at room temperature to yield homogenous
colorless solutions for box-derived complexes or homogenous yellow
solutions for pybox-derived complexes.
(8) (a) Evans, D. A.; Murry, J. A.; Kozlowski, M. C. J. Am. Chem Soc.
1996, 118, 5814-5815. (b) Evans, D. A.; Kozlowski, M. C.; Burgey, C.
S.; MacMilllan, D. W. C. J. Am. Chem Soc. In press.
(9) Enantioselectivities obtained with other [Sn(box)](OTf)2 com-
plexes: [Sn((S,S)-Ph-box)](OTf)2 (91% ee), [Sn((S,S)-iPr-box)](OTf)2 (93%
ee). In contrast, the [Sn(pybox)](OTf)2 complexes (2) proved to be
ineffective catalysts for this reaction.
(14) When this preparative reaction was repeated with 10 mol % catalyst,
the enantioselection was slightly higher (98% ee, 90% yield).
S0002-7863(97)02547-X CCC: $14.00 © 1997 American Chemical Society

10860 J. Am. Chem. Soc., Vol. 119, No. 44, 1997
Communications to the Editor
Table 2. Enantioselective Aldol Reactions between Methyl
Pyruvate and Representative Silylketene Acetals (Eq 6)
of diastereo- and enantiocontrol are observed in the addition of
silylketene acetals derived from ethyl thioesters (entries 5-7,
g95:5 anti:syn, >92% ee).
A further illustration of the capacity of Sn(II) complexes to
achieve high levels of catalyst-substrate organization is presented
in the addition of enolsilanes to unsymmetrical vicinal diketones
(eq 7). The principal issue in this reaction is that of catalyst-
controlled discrimination of methyl- and ethyl-substituted car-
bonyls toward nucleophilic attack. In contrast to the modest
bias for addition to the MeCO-moiety (1.4:1) when catalyzed
by TiCl4 (-78 °C, CH2Cl2), the addition of the (Z) silylketene
acetal 7 to 2,3-pentanedione catalyzed by 2a proceeds with
excellent regioselectivity (97:3), diastereoselectivity (99:1) and
enantioselectivity (98% ee). In comparison, the same reaction
catalyzed by [Cu((S,S)-t-Bu-box)](OTf)2 (9) proceeds with
comparable stereoselection to afford the diastereoisomeric
adduct (regioselectivity 97:3, syn:anti 93:7, 97% ee) (eq 8).8b
a Enolsilane isomeric purity g95%. b Product ratios determined by
HPLC using a Chiralcel OD-H column after hydrolysis of the product
TMS ether (ref 10). c Relative and absolute stereochemical assignments
determined by independent synthesis (see Supporting Information).
d Product configuration assigned by analogy.
effectively catalyze the formation of functionalized succinates
8 with a high degree of stereochemical control (eqs 3 and 4).
The exceptional levels of stereocontrol displayed by (S,S)-
phenyl-pybox complex 2a to afford (R)-8a as a 99:1 anti:syn
mixture in 99% ee and 84% yield (eq 3) established this complex
as the catalyst for further exploration.16 Upon optimization, 2
mol % of 2a at 1.3 M concentration of silylketene acetal and
pyruvate ester was found to catalyze the reaction in 24 h without
a decrease in yield or stereoselectivity. An enantioselectivity/
temperature profile conducted with complex 2a (eq 3) docu-
ments that Sn(II)-pybox catalysts retain stereochemical control
at elevated temperatures (-78 °C, 99:1 anti:syn, 99% ee; 0 °C,
95:5 anti:syn, 86% ee). It is noteworthy that the anti selectivity
observed for this reaction serves to complement the Cu(II)-box
mediated addition of substituted enolsilanes to pyruvate esters
in which syn diastereoselection is observed (eq 5).8b
The X-ray structure of [Sn((S,S)-Ph-pybox)](OTf)2 (2a) is
presented in Figure 1. The crystallographic data for catalyst
2a reveals a ψ-octahedral geometry with distortion of the
oxazoline and triflate ligands away from the stereochemically
active Sn(II) lone pair. Insight into the solution structure(s) of
the ligand-metal species was provided by electrospray ionization
(ESI) studies. Positive mode ESI reveals the presence of [Sn-
(Ph-pybox)2](2+) and [Sn(Ph-pybox)](OTf)(1+), while in the
negative mode, an abundance of triflate ion is observed. These
experiments further highlight the kinetic lability of bisoxazoline
derived Sn(II) complexes toward ligand substitution. Studies
to address the coordination chemistry of related complexes will
be forthcoming.
The catalyzed addition to pyruvates is also general with
respect to the silylketene acetal structure (Table 2, eq 6). Both
(E) and (Z) isomers of the silylketene acetal 7 (entries 1 and 2)
react in a stereoconvergent manner providing the substituted
succinate derivative 8a with excellent overall selectivity (99:1
anti:syn, g96% ee). Variation in the size of the enolsilane alkyl
substituent is possible without significant loss in stereoselectivity
(entries 2-4, >98:2 anti:syn, >97% ee). Finally, high levels
Figure 1. X-ray structure of [Sn(Ph-Pybox)](OTf)2 (2a).
Acknowledgment. Support for this research has been provided by
the NSF. The NIH BRS Shared Instrumentation Grant Program 1-S10-
RR04870 and the NSF (CHE 88-14019) are acknowledged for providing
NMR facilities. Enantiopure amino alcohols were generously provided
by NSC Technologies.
(15) Evidence for bidentate chelation in these reactions is largely
circumstantial. As electrophiles, pyruvate esters and simple aldehydes have
comparable reactivities. In the presence of catalyst 2a, however, addition
of enolsilanes to pyruvate esters is complete within 4 h at -78 °C, while
the use of hydrocinnamaldehyde leads to no reaction at -78 °C and only
50% completion after 72 h at -30 °C (70% ee).
(16) The catalysts were prepared as described above, see ref 7. In a
representative procedure methyl pyruvate (0.50 mmol) and the silylketene
acetal (0.6 mmol) were added sequentially to a catalyst solution in CH2Cl2
(0.8 mL, 0.05 mmol, 10 mol %) at -78 °C. After the reaction was complete
(4-24 h), the mixture was filtered through silica with Et2O, and the silyl
ether was hydrolyzed with 1 N HCl in THF (1 h, 25 °C) to yield the
hydroxyester, which was purified by flash chromatography.
Supporting Information Available: Experimental procedures,
spectral data for all compounds, stereochemical proofs, and X-ray
crystallographic data (16 pages). See any masthead page for ordering
and Internet access instructions.
JA972547S