Highly enantioselective imine hydrosilylation using (S,S)-ethylenebis(η5-tetrahydroindenyl)titanium difluoride

Full text of DOI:10.1021/ja960808c

+
+
6784
J. Am. Chem. Soc. 1996, 118, 6784-6785
Scheme 1
Highly Enantioselective Imine Hydrosilylation Using
(S,S)-Ethylenebis(η5-tetrahydroindenyl)titanium
Difluoride
Xavier Verdaguer, Udo E. W. Lange,
Matthew T. Reding, and Stephen L. Buchwald*
Scheme 2
Department of Chemistry
Massachusetts Institute of Technology
Cambridge, Massachusetts 02139
ReceiVed March 12, 1996
MeOH and pyrrolidine10 were added to 1 and phenylsilane (Vide
infra). Subsequent addition of the imine and stirring at room
temperature or 35 °C yielded the corresponding silylated
amines11 which upon treatment with acid and workup afforded
the enantiomerically enriched free amines.
In the past few years we have developed a number of
titanocene-catalyzed methods for the reduction of imines and
carbonyl containing compounds.1-3 In these procedures the
active catalyst was generated by the addition of 2 equiv of
n-BuLi to the corresponding dichloro or binaphthdiolate ti-
tanocene derivative.4 In this communication we report a more
convenient catalyst activation protocol which proceeds Via an
unprecedented conversion of a Ti-F to a Ti-H. We have
utilized this activation process as an integral step in the
development of the first highly enantioselective catalyst system
for the hydrosilylation of imines.
We recently reported a method for the reduction of lactones
to lactols at room temperature.5 In this system, Cp2Ti(p-
ClC6H4O)2 reacts with polymethylhydrosiloxane (PMHS) in the
presence of TBAF/alumina to afford the active catalyst.
Investigations to clarify the role of the fluoride ion in the
activation process led to a surprising finding. The addition of
phenylsilane to a yellow solution of Cp2TiF2 at room temper-
ature yielded a dark blue solution6 which is catalytically active
for the hydrosilylation of imines (Scheme 1). This experiment
indicated that it is possible, under very mild conditions, to break
the strong Ti-F bond and generate what we believe is a
titanium(III) hydride or its equivalent.6,7 To our knowledge,
the conversion of an early transition metal fluoride to the
corresponding hydride by treatment with a silane has not been
reported.8
To date only a few asymmetric hydrosilylations of imines,
all catalyzed by late transition metal complexes, have been
reported.12 None of these afford amines with high levels of
enantioselectivity. In the light of the efficiency demonstrated
by the Brintzinger-type catalysts for the hydrogenation of
prochiral imines,13 we decided to explore the hydrosilylation
of these substrates using (S,S)-(EBTHI)TiF2 as a precatalyst.
The results obtained for a series of N-methyl and cyclic imines
are shown in Table 1. An important feature of this system is
its experimental simplicity.14 While in the case of the hydro-
genation elevated pressures (80-500 psi) and temperatures (∼65
°C) were required, hydrosilylation reactions are usually carried
out at room temperature under an argon atmosphere. The
catalyst can be activated prior to addition of the substrate or
more conveniently in the presence of the imine (entries 2 and
8). After the reaction is complete, an acidic workup provides
the product secondary amines in high yields and >95% purity
(GC and 1H NMR analysis). The enantioselectivities achieved
in the hydrosilylation of the imines listed in Table 1 are very
high. It is important to point out that the new activation protocol
(10) (a) 1:base:MeOH ) 1:4:4. (b) Pyrrolidine, piperidine, and tBuONa
were all successfully used as bases.
(11) The product silylamines could be observed (NMR) but were never
isolated due to their lability.
(12) (a) Kagan, H. B.; Langlois, N.; Dang, T. P. J. Organomet. Chem.
1975, 90, 353. (b) Becker, R.; Brunner, H.; Mahboobi, S.; Wiegrebe, W.
Angew. Chem., Int. Ed. Engl. 1985, 24. 995. (c) Ojima, I.; Kogure, T.;
Nagai, Y. Tetrahedron Lett. 1973, 14, 2475.
(13) (a) Willoughby, C. A.; Buchwald, S. L. J. Am. Chem. Soc. 1994,
116, 8952. (b) Willoughby, C. A.; Buchwald, S. L. J. Am. Chem. Soc. 1994,
116, 11703
The new activation methodology is also applicable to more
sterically demanding titanocene systems. When (S,S)-ethyl-
enebis(η5-tetrahydroindenyl)titanium difluoride9 1 was treated
with PhSiH3 (Scheme 2), heating to 60 °C yielded a green
solution which was also catalytically active. The same result
was observed at room temperature when a small amount of
(1) (a) Berk, S. C.; Kreutzer, K. A.; Buchwald, S. L. J. Am. Chem. Soc.
1991, 113, 5093. (b) Barr, K. J.; Berk, S. C.; Buchwald, S. L. J. Org. Chem.
1994, 59, 4323.
(14) (a) Typical experimental procedure: A dry resealable Schlenk flask
under argon was charged with (S,S)-(EBTHI)TiF2 (9 mg, 0.025 mmol) and
2 mL of dry THF. To this solution were added Via syringe in this order:
PhSiH3 (0.45 mL, 3.75 mmol), pyrrolidine (8 mL, 0.1 mmol), and methanol
(4 mL, 0.1 mmol). The mixture was stirred at room temperature for 30-60
min resulting in a color change from yellow to green. At this point, the
sealed Schlenk flask was brought into a nitrogen filled glovebox and N-(1-
phenylethylidene)methylamine (332 mg, 2.5 mmol) was added. The Schlenk
was removed from the glovebox, and the reaction mixture was stirred at
room temperature. When consumption of the starting material was complete
(∼12 h), the reaction mixture was diluted with Et2O (20 mL) and stirred
with 1 M HCl (10 mL) for 0.5 h (caution: vigorous bubbling). The aqueous
layer was separated, made basic with 3 M NaOH, and extracted with ether
(3 × 20 mL). The combined ether layers were dried (MgSO4) and
concentrated in Vacuo to yield 319 mg of (S)-(-)-N-methyl-1-phenylethyl-
amine (94% yield, 97% ee). (b) An alternative procedure with in situ
activation of the catalyst proceeds as follows: A dry resealable Schlenk
flask under argon was charged with (S,S)-(EBTHI)TiF2, the imine, and THF.
To this solution were added Via syringe in this order: PhSiH3, pyrrolidine,
and methanol. The reaction mixture was stirred at 35 °C until complete
consumption of starting material was observed. After cooling the reaction
mixture to room temperature, workup and isolation were conducted as
before. (c) N-Methylimines were prepared from the corresponding ketones
with methylamine and TiCl4, see: Evans, D. A.; Domeier, L. A. Organic
Syntheses; Wiley: New York, Collect. Vol. VI, p 818. (d) All imines were
stored in a nitrogen filled glovebox. (e) For reactions employing a 1 mol
% catalyst loading crude N-methylimines and commercially available grade
PhSiH3 (Aldrich) were used. For lower catalyst loadings, imines and PhSiH3
were distilled and stored in an inert atmosphere.
(2) Willoughby, C. A.; Buchwald, S. L. J. Am. Chem. Soc. 1992, 114,
7562.
(3) Carter, M. B.; Schiøtt, B.; Gutierrez, A.; Buchwald, S. L. J. Am.
Chem. Soc. 1994, 116, 11667.
(4) (a) Brintzinger, H. H. J. Am. Chem. Soc. 1966, 88, 4305. (b)
Brintzinger, H. H.; Bercaw, J. E. J. Am. Chem. Soc. 1970, 92, 6182.
(5) Verdaguer, X.; Berk, S. C.; Buchwald, S. L. J. Am. Chem. Soc. 1995,
117, 12641.
(6) A similar color is observed when Cp2TiMe2 reacts with a silane at
room temperature: Xin, S.; Aitken, C.; Harrod, J. F.; Mu, Y. Can. J. Chem.
1990, 68, 471.
(7) For examples of titanium(III) hydrides and silyl titanium hydrides,
see: (a) Xin, S.; Harrod, J. F.; Samuel, E. J. Am. Chem. Soc. 1994, 116,
11562. (b) Wolf, J. M.; Meetsma, A.; Teuben, J. H. Organometallics 1995,
14, 5466. (c) Harrod, J. H.; Yun, S. S. Organometallics 1987, 6, 1381. (d)
Spaltenstein, E.; Palma, P.; Kreutzer, K. A.; Willoughby, C. A.; Davis, W.
A.; Buchwald, S. L. J. Am. Chem. Soc. 1994, 116, 10308.
(8) During the preparation of this manuscript the defluorination of
perfluorocarbons catalyzed by Cp2TiF2 was reported: Kiplinger, J. L.;
Richmond, T. G. J. Am. Chem. Soc. 1996, 118, 1805.
(9) (S,S)-(EBTHI)TiF2 is a crystalline, air-stable yellow-orange solid and
was prepared from the corresponding dichloride derivative in one step,
see: (a) Scha¨fer, A.; Karl, E.; Zsolnai, L.; Gottfried, H.; Brintzinger, H. H.
J. Organomet. Chem. 1987, 328, 87. (b) Bruce, P. M.; Kingston, B. M.;
Lappert, M. F.; Spalding, T. R.; Srivastava, R. C. J. Chem. Soc. (A), 1969,
2106.
S0002-7863(96)00808-6 CCC: $12 00 © 1996 American Chemical Society

+
+
Communications to the Editor
J. Am. Chem. Soc., Vol. 118, No. 28, 1996 6785
Table 1. Catalytic Hydrosilylation of Imines Using
(S,S)-(EBTHI)TiF2
Scheme 3
the rate of catalyst activation. It is known that the reaction
between silanes and alcohols can be catalyzed by an added
base.18 Involvement of a species such as Ph(MeO)SiH2 or
Ph(MeO)2SiH generated in the PhSiH3/MeOH/pyrrolidine mix-
ture could account for the faster rate of catalyst activation. Once
the active catalyst has been generated, the reaction presumably
proceeds by a catalytic cycle similar to that for the titanocene-
catalyzed hydrogenation of imines.13b Insertion of the imine
into the titanium-hydrogen bond of 2 would give the corre-
sponding amido-titanium complex 3. Subsequent σ-bond me-
tathesis of 3 with PhSiH3 Via a four center transition state19
would afford the silylated amine and regenerate the titanium
hydride (Scheme 3). As previously reported, the stereochemical
outcome of the reaction can be rationalized on the basis of the
insertion step.20
In summary, we have developed the first highly enantio-
selective method for the catalytic hydrosilylation of imines. This
experimentally simple system features a novel activation process
based on the reaction of (S,S)-(EBTHI)TiF2 with phenylsilane.
The procedure converts imines to amines under mild conditions
with significantly higher subtrate:catalyst ratios than previously
possible. Further work aimed at the elucidation of the mech-
anism and broadening the scope of these reactions is currently
in progress.
a The absolute configurations for the product amines in entries 1, 2,
3, 6, and 8 were determined by polarimetry. The absolute configuration
for the product in entry 9 was assigned by analogy to 2-phenylpyrro-
lidine in entry 8. b Yields refer to isolated compounds of >95% purity
by GC and 1H NMR. c Unless otherwise noted ee (%) were determined
by GC analysis of the corresponding trifluoroacetamides on a Chiraldex
G-TA column. d Enantiomeric excess determined by GC analysis of
the trifluoroacetamide derivative on a Chiraldex B-PH column. e E-
nantiomeric excess determined by combined analysis of the bis(tri-
fluoroacetamide) derivative on a Chiralcel OD HPLC column and HP-1
GC column. f Chiral GC analysis revealed 1100/1 ratio of the corre-
sponding enantiomers. g In situ catalyst activation was used.
Acknowledgment. This work was supported by the National
Institutes of Health. X.V. thanks the Spanish Ministry of Education
and Science for a postdoctoral fellowship. U.L. thanks the Deutsche
Forschungsgemeinschaft for a postdoctoral fellowship. We are grateful
to B. Chin for the preparation of 1. We thank N. Radu for insightful
comments and Professor Mark Burk for information on chiral GC
analysis.
Supporting Information Available: Detailed experimental pro-
cedures and spectral data for (S,S)-ethylenebis(η5-tetrahydroindenyl)-
titanium difluoride and compounds listed in Table 1 (10 pages). See
any current masthead page for ordering and Internet access instructions.
has allowed us to decrease the catalyst loading to as little as
0.02-0.1 mol % with no effect on the yield or the enantiomeric
purity of the resulting amines (entries 1, 2, 6, and 8).
Furthermore, the reaction tolerates an aromatic chloride (entry
2) and the presence of a ferrocenyl moiety (entry 7). In addition,
the successful reduction of a cyclopropyl imine is evidence
against a radical process (entry 5).15 Finally, as shown in entry
9 this procedure can be also applied to the synthesis of chiral
amines which contain multiple stereogenic centers.
At the present time the nature of the activation process is
unclear. From a thermochemical point of view, the unusually
high Si-F (150-166 kcal/mol) bond energy could be considered
the driving force responsible for the Ti-F (140 Kcal/mol) bond
cleavage.16,17 Related with this is the observation that a small
amount10a of methanol and a base such as pyrrolidine enhance
JA960808C
(16) D (F3Ti-F) ) 140 kcal/mol, D (H3Si-F) ) 150 kcal/mol, D (F3-
Si-F) ) 166 kcal/mol, see: (a) Connor, J. A. Top. Curr. Chem. 1977, 71,
71. (b) Schock, L. E.; Marks, T. J. J. Am. Chem. Soc. 1988, 110, 7701. (c)
Walsh, R. in The Chemistry of Organic Silicon Compounds; Patai, S.,
Rappoport, Z., Eds.; John Wiley & Sons: New York, 1989.
(17) To our knowledge accurate bond energies for Ti-H have not been
reported; therefore, a complete balanced thermochemical calculation is not
possible.
(18) For examples of base-catalyzed dehydrocondensation of silanes with
alcohols, see: (a) Lukevics, E.; Dzintara, M. J. Organomet. Chem. 1984,
271, 307. (b) Gilman, H.; Dunn, G. E.; Hartzfeld, H.; Smith, A. G. J. Am.
Chem. Soc. 1955, 77, 1287. (c) Bazant, V.; Chvalovsky, V.; Rathousky, J.
In Organosilicon Compounds; Publishing House of the Czechoslovak
Academy of Science: Prague, 1965; pp 54-56.
(19) Woo, H-G.; Tilley, T. D. J. Am. Chem. Soc. 1989, 111, 8043.
(20) The absolute configuration of the major enantiomer observed in the
hydrosilylation coincides with the one obtained from the hydrogenation
reaction.13b
(15) Griller, D.; Ingold, K. U. Acc. Chem. Res. 1980, 13, 317.