Catalytic, enantioselective addition of substituted allylic trichlorosilanes using a rationally-designed 2,2′-bispyrrolidine-based bisphosphoramide [23]

Full text of DOI:10.1021/ja016552e

9488
J. Am. Chem. Soc. 2001, 123, 9488-9489
Scheme 1
Catalytic, Enantioselective Addition of Substituted
Allylic Trichlorosilanes Using a Rationally-Designed
2,2′-Bispyrrolidine-Based Bisphosphoramide
Scott E. Denmark* and Jiping Fu
Roger Adams Laboratory, Department of Chemistry
UniVersity of Illinois, Urbana, Illinois 61801
ReceiVed July 5, 2001
The enantioselective addition of allylmetal reagents to alde-
hydes is an often-employed and powerful method for stereose-
lective carbon-carbon bond formation.1 The overwhelming
majority of examples that operate catalytically are chiral Lewis
acid-promoted additions of allylic silanes and stannanes which
often proceed with excellent enantioselectivity.2 However, these
transformations are less useful for the introduction of γ-substituted
allylic species, because the open-transition structure characteristic
of these reactions does not allow for controlled diastereoselection.3
A mechanistically distinct approach that addresses the problem
of relative diastereocontrol is the Lewis base-promoted addition
of allylic trichlorosilanes to aldehydes.4,5 In 1994, the first exam-
ples of catalytic enantioselective addition of allylic trichlorosilanes
to aldehydes by the use of chiral phosphoramides was reported
from these laboratories (Scheme 1).6 Since then, a number of
groups have reported enantioselective additions promoted by chiral
phosphoramides,7a,b formamides,7c,d N-oxides,7e ureas,7f and di-
amines.7g Despite significant efforts at empirical optimization of
the enantioselectivity, a highly selective and reactive catalyst has
yet to be discovered. Herein, we report the design and implemen-
tation of a new 2,2′-bispyrrolidine-based bisphosphoramide that
catalyzes the addition of many kinds of allylic trichlorosilanes to
aldehydes with excellent diastereo- and enantioselectivity. We
also report the first examples of catalytic, enantioselective
construction of quaternary carbon centers by this technology.
Mechanistic studies on the allylation promoted by phosphor-
amide 3 indicated that the reaction can proceed by two pathways
involving either one or two phosphoramides bound to the
chlorosilane.8 An important consequence of this duality is that
the rate of the more selective “two-phosphoramide” pathway
decreases as [cat]2. Thus, at catalytic loadings, the rate and
selectivity (due to the intervention of the one-phosphoramide
pathway) of the addition are adversely affected. This problem
was addressed by utilizing bisphosphoramide 5 with the expecta-
tion of increasing the effective concentration of the second catalyst
molecule through proximity (Chart 1). A systematic investigation
of the tether revealed that bisphosphoramide 5d (in which the
two base functions are separated by a five-methylene unit) was
able to provide a higher, yet still modest ee (72%).
Chart 1
Further modifications of the catalyst structure focused on the
evaluation of dimeric phosphoramides with various chiral di-
amines as backbones. Employment of dimeric versions of catalysts
that have served well in other processes were largely ineffective
here.9 To refine our understanding of the origin of asymmetric
induction and assist in the design of more selective catalysts, we
utilized SnCl4 as a surrogate for silicon to study the complexation
of a bisphosphoramide to a Lewis acid.10 Examination of the X-ray
(1) For recent reviews of allylmetal additions see: (a) Denmark, S. E.;
Almstead, N. G. In Modern Carbonyl Chemistry; Otera, J., Ed.; Wiley-VCH:
Weinheim, 2000; Chapter 10. (b) Chemler, S. R.; Roush, W. R. In Modern
Carbonyl Chemistry; Otera, J., Ed.; Wiley-VCH: Weinheim, 2000; Chapter
11. (c) StereoselectiVe Synthesis, Methods of Organic Chemistry (Houben-
Weyl), Edition E21; Helmchen, G., Hoffmann, R., Mulzer, J., Schaumann,
E., Eds.; Thieme: Stuttgart, 1996; Vol. 3, pp 1357-1602. (d) Yamamoto,
Y.; Asao, N. Chem. ReV. 1993, 93, 2207.
(2) For a review of Lewis acid-catalyzed allylmetal additions see:
Yanagisawa, A. In ComprehensiVe Asymmetric Catalysis; Jacobsen, E. N.,
Pfaltz, A., Yamamoto, H., Eds.; Springer-Verlag: Heidelberg, 1999; Vol. II,
Chapter 27.
(3) (a) Denmark, S. E.; Almstead, N. G. J. Org. Chem. 1994, 59, 5130.
(b) Denmark, S. E.; Hosoi, S. J. Org. Chem. 1994, 59, 5133. (c) Keck, G. E.;
Savin, K. A.; Cressman, E. N. K.; Abbott, D. E. J. Org. Chem. 1994, 59,
7889. (d) Keck, G. E.; Dougherty, S. M.; Savin, K. A. J. Am. Chem. Soc.
1995, 117, 6210.
(4) (a) Sakurai, H. Synlett 1989, 1. (b) Sakurai, H. In Proceedings of the
5th International Kyoto Conference on New Aspects of Organic Chemistry;
Yoshida, Z.-I., Ohshiro, Y., Eds.; Kodansha Press: Tokyo, Japan, 1992; pp
129-157 and references therein. (c) Kira, M.; Zhang, L.; Kabuto, C.; Sakurai,
H. Organometallics 1996, 15, 5335.
11
crystal structure of 5d‚SnCl4 revealed that the disposition of
the internal, N-methyl substituents was significantly influenced
by the chiral skeleton (Figure 1a). We reasoned that connecting
the substituent on the stereogenic center to the nitrogen atom by
enclosure in a ring should enforce a more rigid control of the
orientation of the N-substituents and thus impose a more highly
dissymmetric coordination environment. This notion of backbone-
induced nitrogen distortion is presented in Figure 1b,c, and thus
suggested the use of a phosphoramide derived from 2,2′-
bispyrrolidine.12
(5) (a) Kobayashi, S.; Nishio, K. Tetrahedron Lett. 1993, 34, 3453. (b)
Kobayashi, S.; Nishio, K. Synthesis 1994, 457. (c) Kobayashi, S.; Nishio, K.
J. Org. Chem. 1994, 59, 6620. For additions to hydrazones, see: (d) Kobayashi,
S.; Hirabayashi, R. J. Am. Chem. Soc. 1999, 121, 6942. For propargylation,
see: (e) Kobayashi, S.; Nishio, K. J. Am. Chem. Soc. 1995, 117, 6392.
(6) Denmark, S. E.; Coe, D. M.; Pratt, N. E.; Griedel, B. D. J. Org. Chem.
1994, 59, 6161.
We were delighted to find that the dimeric bisphosphoramides
6a-c induced the allylation of benzaldehyde at -78 °C with just
5 mol % loading. For this series as well, the dimer 6b with a
five-methylene tether provided superior selectivity and reactivity
(7) (a) Iseki, K.; Kuroki, Y.; Takahashi, M.; Kobayashi, Y. Tetrahedron
Lett. 1996, 37, 5149. (b) Iseki, K.; Kuroki, Y.; Takahashi, M.; Kishimoto, S.;
Kobayashi, Y. Tetrahedron 1997, 53, 3513. (c) Iseki, K.; Mizuno, S.; Kuroki,
Y.; Kobayashi, Y. Tetrahedron Lett. 1998, 39, 2767. (d) Iseki, K.; Mizuno,
S.; Kuroki, Y.; Kobayashi, Y. Tetrahedron 1999, 55, 977. (e) Nakajima, M.;
Saito, M.; Shiro, M.; Hashimoto, S. J. Am. Chem. Soc. 1998, 120, 6419. (f)
Chataigner, I.; Piarulli, U.; Gennari, C. Tetrahedron Lett. 1999, 40, 3633. (g)
Angell, R. M.; Barrett, A. G. M.; Braddock, D. C.; Swallow, S.; Vickery, B.
D. Chem. Commun. 1997, 919.
(8) Denmark, S. E.; Fu, J. J. Am. Chem. Soc. 2000, 122, 12021.
(9) 1,1′-Binaphthyl-2,2′-diamine: (a) Denmark, S. E.; Barsanti, P. A.;
Wong, K.-T.; Stavenger, R. A. J. Org. Chem. 1998, 63, 2428. Stilbene-1,2-
diamine: (b) Denmark, S. E.; Stavenger, R. A.; Wong, K.-T.; Su, X. J. Am.
Chem. Soc. 1999, 121, 4982.
(10) For previous studies see: Denmark, S. E.; Su, X. Tetrahedron 1999,
55, 8727.
(11) The crystallographic coordinates of 5d‚SnCl4 have been deposited with
the Cambridge Crystallographic Data Centre; deposition no. CCDC 164277.
10.1021/ja016552e CCC: $20.00 © 2001 American Chemical Society
Published on Web 08/28/2001

Communications to the Editor
J. Am. Chem. Soc., Vol. 123, No. 38, 2001 9489
Table 2. Allylations Catalyzed by 6ba
entry silanesb
R
yield, % syn/antic ee, %d
1
2
1a
1a
1a
1a
1a
1a
1b
1b
1b
1c
1c
1c
1c
1c
1c
1c
1d
1d
1d
Ph
85
92
84
79
86
59
82
83
57
89
88
91
85
78
62
82
89
70
71
87e
87e
88e
80e
81e
81e
86e
81
2-naphthyl
4-CH3OC6H4
4-CF3C6H4
(E)-C6H5CHdCH
2-furyl
3
Figure 1. (a) Chem 3D image of 5d‚SnCl4. Most hydrogens removed for clarity.
(b) Nitrogen distortion in the hypothetical complex of phosphoramides 6/7. (c)
Front view.
4
5
6
7
Ph
1/99
1/99
1/99
99/1
99/1
99/1
99/1
99/1
95/5
99/1
8
2-naphthyl
(E)-C6H5CHdCH
Ph
compared to the bisphosphoramides 6a and 6c with different tether
lengths and the monophosphoramide 7 (Table 1).13 The strong
cooperativity of the dimers and enhanced selectivity of 6b
compared to 7 support the hypothesis of a two-phosphoramide
pathway.
9
80
10
11
12
13
14
15
16
17
18
19
94e
94
2-naphthyl
4-CH3OC6H4
4-CF3C6H4
(E)-C6H5CHdCH
(E)-C6H5CHdC(CH3)
2-furyl
94
82
88
92
95
96e
88
Table 1. Allylation of Benzaldehyde with 1a Catalyzed by
2,2′-Bispyrrolidine-Derived Phosphoramidesa
Ph
(E)-C6H5CHdCH
2-furyl
95
entry
catalyst
ee, %b
yield, %
a Reactions done at -78 °C for 8-10 h with 5 mol % of 6b. b 1b and
1c both >99/1 isomerically pure by 1H NMR analysis. c Determined by 1H
NMR (400 or 500 MHz) analysis. d Determined by CSP-SFC or chiral CSP-
GC. e Absolute configuration assigned by comparison to the literature value
of optical rotation; see Supporting Information.
1
6a
6b
6c
7
18 (S)
87 (S)
67 (S)
56 (S)
54
85
58
56
2
3
4c
a All reactions run at 1.0 M concentration in CH2Cl2/i-Pr2NEt, 1/1 at
and nerol, respectively, in geometrically pure form in two steps.5c
The catalyzed addition of these agents to benzaldehyde provided
adducts anti-9 and syn-9 with excellent diastereo- and enantio-
selectivities (Scheme 2). Since the γ-disubstituted allylic alcohols
are widely accessible, this method represents a versatile route
for the construction of quaternary stereogenic centers.15
b
c
-78 °C for 8 h, using 5 mol % catalyst. Determined by CSP-SFC. 20
mol % catalyst was used.
With an efficient catalyst in hand, we explored the scope of
the allylation with various aldehydes (Table 2). Aromatic, hetero-
aromatic, and unsaturated aldehydes underwent allylation in good
yields and selectivities (Table 2, entries 1-6). However, the more
important demonstration of scope was in the extension to the reac-
tions of γ-substituted allylic trichlorosilanes. The additions of (E)-
or (Z)-2-butenyltrichlorosilanes (1b and 1c) are known to be high-
ly diastereoselective and the results with 6b were no exception
(entries 7-16). The proposed chairlike transition structure for
these additions is apparently operative as reflected in the excellent
correlation of geometrical purity of the silanes with the diaster-
eomeric composition of the products (E f anti; Z f syn). The
results in Table 2 show clearly that 1c leads to much higher
enantioselectivity compared to 1b. Furthermore, γ-disubstituted
allylic trichlorosilane 1d also reacted under these conditions to
provide prenylation products with excellent selectivity (Table 2,
entries 17-19). Apparently, the Z-substituent on the allylic tri-
chlorosilane has a beneficial effect as evidenced by the highly
selective syn-butenylation and prenylation processes. Further, elec-
tron rich aldehydes seemed to react with higher enantioselectivities
compared to electron poor substrates (cf. entries 3 vs 4, 12 vs 13).
The successful and highly enantioselective addition of 1d
promoted by 6b, together with the strong stereochemical coupling
of geometry with diastereoselectivity (for 1b and 1c), suggested
the opportunity to construct quaternary stereogenic centers14 by
the addition of unsymmetrically γ-disubstituted allylic trichloro-
silanes to aldehydes. As test substrates we chose trisubstituted
silanes (E)-8 and (Z)-8, which were synthesized from geraniol
Scheme 2
In summary we have developed a highly efficient bisphos-
phoramide catalyst (derived from readily available (R,R)-2,2′-
bispyrrolidine) for the addition of allylic trichlorosilanes to
aldehydes. This catalyst effectively promotes the diastereo- and
enantioselective addition of various γ-substituted silanes to
unsaturated aldehydes at low loadings and in high yield. Further
extension of the reaction to aliphatic aldehydes and the application
to problems in synthesis are under investigation.
Acknowledgment. We are grateful to the National Science Foundation
(NSF CHE 9803124) for the support of this research. J.F. thanks
Boehringer Ingelheim Pharmaceutical Company for a graduate fellowship.
Supporting Information Available: Full characterization of all
catalysts and products, procedures for the preparation of (R,R)-2,2′-
bispyrrolidine, 6a-6c, 7, (E)-8, and (Z)-8, along with a general procedure
for the addition reaction (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
(12) The preparation of (R,R)-2,2′-bispyrrolidine was easily accomplished
on a large scale by photodimerization of pyrrolidine followed by resolution
with tartaric acid; see Supporting Information. For photodimerization of
pyrrolidine see: (a) Krajnik, P.; Ferguson, R. R.; Crabtree, R. H. New J. Chem.
1993, 17, 559. (b) Ferguson, R. R.; Boojamra, C. G.; Brown, S. H.; Crabtree,
R. H. Heterocycles 1989, 28, 121. For resolution of bispyrrolidine see: (c)
Oishi, T.; Hirama, M.; Sita, L. R.; Masamune, S. Synthesis 1991, 789. For
alternative syntheses see: (d) Alexakis, A.; Tomassini, A.; Chouillet, C.;
Roland, S.; Mangeney, P.; Bernardinelli, G. Angew. Chem., Int. Ed. Engl.
2000, 39, 4093. (e) Kotsuki, H.; Kuzume, T.; Ghoda, H.; Fukuhara, M.; Ochi,
M.; Oishi, T.; Hirama, M.; Shiro, M. Tetrahedron: Asymmetry 1995, 6, 2227.
(13) It is interesting to note that the X-ray structure of 5d‚SnCl4 also reveals
the probable basis for the superiority of the (CH2)5 tether in that the methylenes
can occupy a nicely staggered syn-pentane alignment.
JA016552E
(14) For a review on catalytic enantioselective construction of quaternary
centers see: Corey, E. J.; Guzman-Perez, A. Angew. Chem., Int. Ed. Engl.
1998, 37, 388.
(15) The absolute configuration of the products was assured by X-ray
crystallography of the 4-bromobenzoate derivative of the adduct of (E)-8 with
2-naphthaldehyde, see Supporting Information.