Tandem catalytic asymmetric ring-opening metathesis/cross metathesis [19]

Full text of DOI:10.1021/ja9931832

J. Am. Chem. Soc. 1999, 121, 11603-11604
11603
Scheme 1
Tandem Catalytic Asymmetric Ring-Opening
Metathesis/Cross Metathesis
Daniel S. La,† J. Gair Ford,† Elizabeth S. Sattely,†
Peter J. Bonitatebus,‡ Richard R. Schrock,‡ and
Amir H. Hoveyda*,†
Department of Chemistry, Merkert Chemistry Center
Boston College, Chestnut Hill, Massachusetts 02467
Department of Chemistry
Massachusetts Institute of Technology
Cambridge, Massachusetts 02139
Table 1. Tandem Mo-Catalyzed Asymmetric Ring-Opening/Cross
Metathesesa
ReceiVed September 3, 1999
Metal-catalyzed metathesis is a powerful method in chemical
synthesis.1 Different versions of this important transformation
include catalytic ring-closing, ring-opening,2 and cross metathesis;3
several approaches have been devised that employ these processes
in combination.4 With the availability of chiral complexes 1a,
1b,5 and 2,6 which promote efficient asymmetric ring-closing
a Conditions: 5 mol % 1a, 2 equiv of 4, Ar atm, 22 °C, C6H6.
b Percent product determined by 400 MHz 1H NMR analysis. c Deter-
mined by 400 MHz 1H NMR analysis. d Isolated yield of purified
products by silica gel chromatography. e Determined by HPLC (Chiral-
cel OD for entries 1, 2, 4-7 and AD chiralpak for entries 8-9), in
comparison with authentic racemic materials. Analysis of products in
entries 1, 4, 6, and 7 were performed on the derived acetates.
silyl ether 3,7 which was prepared and treated with styrene (4a)
in the presence of 5 mol % 1a, 1b, and 2. The biphen-based
complex 1a proves to be superior (Scheme 1); catalytic AROM/
CM proceeds in the presence of 10 equiv of styrene and 5 mol
% 1a to 39% conversion (22 °C, C6H6). Importantly, the desired
product (5a) is obtained in >98% ee and as a single olefin isomer
metathesis (ARCM), we wish to develop other catalytic asym-
metric metathesis reactions. A major aspect of our program thus
relates to the design of enantioselective protocols that involve
the tandem occurrence of different metathesis-based processes.
Herein, we report the results of our initial studies on tandem Mo-
catalyzed asymmetric ring-opening/cross metathesis reactions
(catalytic AROM/CM). The present method allows access to
unsaturated carbocycles, which are formed in high yield, as single
olefin isomers and in excellent enantiopurity. To the best of our
knowledge, this disclosure documents the first examples of a
catalytic AROM.
We initiated our studies by examining the possibility of
effecting catalytic AROM/CM with norbornene and styrene in
the presence of 1a, 1b, and 2. All attempts resulted in the
formation of substantial amounts of poly(norbornene), even in
the presence of excess styrene. Accordingly, to discourage
polymerization, we decided to use the sterically more encumbered
1
(GLC and H NMR analysis, respectively).
Subsequent studies indicated that lower concentrations of
styrene result in higher conversions.8 Thus, with 1a as the catalyst
and with 5 equiv of styrene, 52% conversion is observed; with 2
equiv of styrene, >77% conversion is attained. As shown in entry
1 of Table 1, treatment of 3 with 2 equiV of styrene (4a) in the
presence of 5 mol % 1a at 22 °C for 7 h affords 5a in 57%
isolated yield and 96% ee (>98% trans). The stereochemical
identity of the catalytic AROM/CM product 5b was established
through determination of the crystal structure of the corresponding
camphor sulfonate derivative (see the Supporting Information).
† Boston College.
‡ Massachusetts Institute of Technology.
The results of our studies involving the Mo-catalyzed AROM/
CM of various norbornene and styrene derivatives are summarized
in Table 1. Regardless of the electronic proprties of the styrene
partner (4a, 4b, or 4c), reactions can be designed to proceed in
high conVersion to afford 5, 7, and 9 with complete control of
olefin stereochemistry (>98% trans), in good yield and high
optical purity (>91% ee).9 A number of related issues are worthy
of note: (1) Catalytic AROM/CM reactions can be carried out
with catalyst loadings lower than 5 mol %; for example, with 1
(1) Armstrong, S. K. J. Chem. Soc., Perkin Trans. 1 1998, 371-388.
(2) For representative recent reports on Ru-catalyzed ROM, see: (a)
Snapper, M. L.; Tallarico, J. A.; Randall, M. L. J. Am. Chem. Soc. 1997, 119,
9, 1478-1479. (b) Schneider, M. F.; Lucas, N.; Velder, J.; Blechert, S. Angew.
Chem., Int. Ed. Engl. 1997, 36, 257-259.
(3) (a) Crowe, W. E.; Goldberg, D. R. J. Am. Chem. Soc. 1995, 117, 5162-
5163. (b) For a recent review of catalytic CM, see: (b) Gibson, S. E. In Alkene
Metathesis in Organic Synthesis; Furstner, A., Ed.; Springer, Berlin 1998; pp
155-180.
(4) For examples of non-asymmetric tandem catalytic ROM/RCM, see: (a)
Harrity, J. P. A.; La, D. S.; Cefalo, D. R.; Visser, M. S.; Hoveyda, A. H. J.
Am. Chem. Soc. 1998, 120, 2343-2351. (b) Johannes, C. W.; Visser, M. S.;
Weatherhead G. S.; Hoveyda, A. H. J. Am. Chem. Soc. 1998, 120, 8340-
8347. For examples of nonasymmetric tandem catalytic ROM/CM, see: (c)
Randall, M. L.; Tallarico, J. A.; Snapper, M. L. J. Am. Chem. Soc. 1995, 117,
9610-9611. (d) Reference 2b.
(5) (a) Alexander, J. B.; La, D. S.; Cefalo, D. R.; Hoveyda, A. H.; Schrock,
R. R. J. Am. Chem. Soc. 1998, 120, 4041-4042. (b) La, D. S.; Alexander, J.
B.; Cefalo, D. R.; Graf, D. D.; Hoveyda, A. H.; Schrock, R. R. J. Am. Chem.
Soc. 1998, 120, 9720-9721.
(6) Zhu, S.; Cefalo, D. R.; La, D. S.; Jamieson, J. Y.; Davis, W. M.;
Hoveyda, A. H.; Schrock, R. R. J. Am. Chem. Soc. 1999, 121, 8251-8259.
(7) Gerteisen, T. J.; Kleinfelter, D. C. J. Org. Chem. 1971, 36, 3255-
3259.
(8) The reason for this observation is unclear at the present time.
(9) The stereochemical identity of all products in Table 1 and Scheme 2 is
consistent with the assignment made based on the X-ray structure (cf. Figure
1). Selected products from all substrates were converted to common intermedi-
ates (derived acetates in place of silyl or MOM ethers) and compared by chiral
HPLC.
10.1021/ja9931832 CCC: $18.00 © 1999 American Chemical Society
Published on Web 11/30/1999

11604 J. Am. Chem. Soc., Vol. 121, No. 49, 1999
Communications to the Editor
mol % 1a, 7b is formed in >98% ee and 92% yield (>98% trans,
5 h). (2) Toluene may be used as solvent; the reaction in entry 7
proceeds in toluene to afford 9a in 86% isolated yield and >99%
ee (0.3 h). (3) In general, catalytic AROM/CM are faster with
more electron-rich styrenes. Thus, as shown in entries 1-3 of
Table 1, transformations with 4a and 4b proceed to >75% conv
within 7 h, whereas reaction with 4c proves to be prohibitively
slow. Nevertheless, as the alkene unit of the norbornene substrate
becomes more sterically accessible, catalytic AROM/CM of the
slower reacting and electron-deficient 4c reaches synthetically
useful levels of efficiency (entries 6 and 9). (4) With the exception
of the reaction shown in entry 5, varying amounts of 10, 11, and
12 are isolated as minor byproducts.10 If transformations are
Scheme 3
CHR (ii) or the less substituted LnModCH2 (iii); each of these
two complexes may then promote catalytic AROM. Initiation with
ii generates iv, which can undergo catalytic CM to afford vi.
Alternatively, reaction through Mo-alkylidene iii would generate
ent-vi via alkylidene viii. If AROM occurs with the same sense
of stereocontrol with ii and iii, then reaction with ii would afford
vi, whereas that with iii would yield ent-vi. (2) One olefinic
substrate (i, Scheme 3) must be more reactive, so that AROM
occurs efficiently and effectively competes with homo-metathesis
of the other alkene (v). (3) Terminal alkene substrates need to be
sterically and electronically12 compatible; if not, competitive
catalytic CM might occur to reduce overall efficiency (e.g., homo-
metathesis of v or CM of iv + vi). (4) The terminal alkene
substrate (v) should be selected so that its reaction with iv or viii
proceeds with the appropriate regiocontrol during metallacyclobu-
tane formation; otherwise, the undesired achiral meso adducts vii
or ix will form.
allowed to proceed for extended times (see Table 1), more of 10
(CM between product molecules) and 11 (CM between 4 and
product) are formed.
Our attempts to use aliphatic olefin substrates in catalytic
AROM/CM reactions have been promising but less successful.
When vinyl cyclohexane 13 is employed with silyl ether 6 (eq
1), diene 14 is formed with diminished efficiency and enantiose-
Scheme 4
lectivity (36% isolated yield, 82% ee);1H NMR analysis of the
unpurified reaction mixture indicates 30% of byproducts related
to 11 and 12 and 34% recovered 6. However, as illustrated in
Scheme 2, catalytic processes with vinylsilanes afford optically
pure materials in an efficient manner. Treatment of 8 with 5 mol
% 1a and one equiv of 15 (50 °C, 85% conversion, 24 h) leads
to the formation of vinylsilane 16 in >98% ee and 62% purified
yield (>98% trans by 400 MHz 1H NMR). When trialkoxysilane
17 is utilized, catalytic AROM/CM is more efficient (>98%
conversion, 22 °C, 24 h). The resulting vinylsilane 18 (>98%
ee) undergoes Pd-catalyzed cross coupling with various aryl
iodides to afford a wider range of optically pure adducts.11 The
example shown in Scheme 2 is illustrative (8f19; 51% overall).
Mode of addition I, presented in Scheme 4, may be suggested
as one plausible working model for the formation of the major
enantiomer. In the alternative II, leading to the minor enantiomer,
there is significant unfavorable steric strain between the substrate
and the imido ligand of the chiral catalyst. The lower selectivity
observed in reactions catalyzed by 1b is consistent with this
proposal: with the smaller Me groups on the imido ligand (vs
i-Pr), reaction pathway through II is less disfavored. The
suggestion that LnModC(H)Ph, and not the corresponding Ln-
ModCH2, is the active catalyst is based on the fact that treatment
of 1a with 40 equiv of styrene13 leads to <2% stilbene formation
and the immediate generation of LnModC(H)Ph, as judged by
the appearance of new alkylidene resonances at 11.50 and 13.05
ppm (3:1, syn and anti isomers,6 respectively; 400 MHz, C6D6).
Detailed mechanistic investigation is in progress; in addition to
the above issues, these studies aim to determine whether the
bridgehead alkoxide is involved in chelation with the Lewis acidic
Mo.14
Scheme 2
Supporting Information Available: Experimental procedures and
spectral and analytical data for all reaction products (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
JA9931832
A general pathway for the catalytic AROM/CM is proposed
(Scheme 3). Several intricate issues regarding the suggested
mechanism merit mention: (1) The initial Mo-neophylidene (e.g.,
1a) may react with the terminal alkene (v) to generate LnMod
(12) Crowe, W. E.; Zhang, Z. J. J. Am. Chem. Soc. 1993, 115, 10998-
10999.
(13) The ratio of 1a: styrene (4a) was selected so as to mimic the conditions
in Table 1.
(14) This research was generously supported by the NSF (CHE-9905806
to A. H. H.; CHE-9700736 to R. R. S.) and the NIH (GM-47480 to A.H.H.).
D. S. L. is grateful for a graduate fellowship by the American Chemical Society
(sponsored by Boehringer-Ingelheim).
(10) The difference between total conversion and conversion to product
constitutes the percent byproduct formation.
(11) Tamao, K.; Kobayashi, K.; Ito, Y. Tetrahedron Lett. 1989, 30, 6051-
6054.