Highly enantioselective hydrosilylation/cyclization of 1,6-enynes catalyzed by rhodium(I) complexes of spiro diphosphines

Article abstract of DOI:10.1002/anie.200603533

(Chemical Equation Presented) Highly enantioselective synthesis: The rhodium(I) complex of the chiral ligand SDP is successfully used as a catalyst for the hydrosilylation/cyclization of 1,6-enynes with silanes. Under the optimized reaction conditions, op

Full text of DOI:10.1002/anie.200603533

Angewandte
Chemie
DOI: 10.1002/anie.200603533
Asymmetric Catalysis
Highly Enantioselective Hydrosilylation/Cyclization of 1,6-Enynes
Catalyzed by Rhodium(I)Complexes of Spiro Diphosphines**
Bao-Min Fan, Jian-Hua Xie, Shen Li, Li-Xin Wang, and Qi-Lin Zhou*
The transition-metal-catalyzed cyclization of 1,6-enynes has
been extensively studied and has emerged as an efficient and
atom-economic method for the construction of five-mem-
bered carbocyclic and heterocyclic frameworks.[1] These
structures exist in many natural products and biologically
active compounds, and the synthesis of nonracemic com-
pounds containing these rings has given an impetus to
chemists to design and develophighly efficient synthetic
protocols. Prompted by the work of Trost,[2] asymmetric
cyclizations of 1,6-enynes catalyzed by chiral palladium[3] and
rhodium complexes[4] have been realized and excellent
enantioselectivities (upto 99% ee) have been achieved in
recent years. However, the silylcyclization of 1,6-enynes,
which was first reported by Ojima et al. in 1992,[5] was less
successful. This tandem hydrosilylation/cyclization reaction
employs silane as a stoichiometric reductant and is a
synthetically useful transformation that allows the formation
of both a carbocycle and a carbon–silicon bond.[6] In 2003,
Widenhoefer and co-workers reported the first, and so far the
only, example of the asymmetric silylcyclization of 1,6-enynes
by using a rhodium complex of 6,6’-bis(diphenylphosphino)-
2,2’-dimethylbiphenyl (BIPHEMP) as a catalyst and obtained
the silylalkylidene cyclopentanes in good enantioselectivities
(77–92% ee).[7]
Recently we developed a new type of chiral phosphorus
ligands containing a 1,1’-spirobiindane scaffold and demon-
strated that they are highly enantioselective for rhodium- or
ruthenium-catalyzed asymmetric hydrogenation[8] and other
transition-metal-catalyzed asymmetric reactions.[9] Among
the chiral spiro phosphorus ligands studied, N-dimethyl(1,1’-
spirobiindane-7,7’-diyl)phosphoramidite (SIPHOS) and 7,7’-
bis(diphenylphosphino)-1,1’-spirobiindane (SDP) were found
to be efficient for the asymmetric rhodium-catalyzed Pauson–
Khand reaction, converting 1,6-enynes into bicyclopentenone
derivatives under a CO atmosphere in high yields with good
enantioselectivities.[10] Encouraged by this result, we decided
to investigate the asymmetric rhodium-catalyzed silylcycliza-
tion of 1,6-enynes by using chiral spiro phosphorus ligands in
order to developefficient methods for the synthesis of
optically active functionalized carbocyclic and heterocyclic
compounds. Herein, we wish to report an asymmetric
silylcyclization of 1,6-enynes catalyzed by rhodium complexes
of SDP with excellent enantioselectivities (upto 99.5% ee).
The asymmetric silylcyclization reaction of 1,6-enyne 1a
with 5 equivalents of HSiEt3 (2a) was chosen to optimize the
reaction conditions (Table 1). The reaction was carried out in
Table 1: Optimization of the reaction conditions for the rhodium-
catalyzed asymmetric silylcyclization of 1a with silane 2a.[a]
Entry
Ligand
T [8C]
t [h]
Yield [%][b]
ee [%][c]
1
2
3
4
(R)-SDP
(R)-SDP
(R)-SDP
(R)-SDP
70
RT
50
90
70
70
70
70
70
70
70
70
2.0
24.0
3.5
0.5
2.0
0.5
0.5
2.0
3.0
1.0
3.0
3.0
60
43
62
59
58
56
53
56
50
34
–
98
94
96
96
96
87
96
89
88
83
–
5[d]
6
(R)-SDP
(R)-Tol-SDP
(R)-An-SDP
(R)-Xyl-SDP
(S)-BINAP
(R)-SYNPHOS
(R,R)-Me-DuPHOS
(R,S)-JOSIPHOS
7
8
9
10
11
12
18
38
[a] Reaction conditions: 2a/1a/[Rh(cod)2]BF4/L=5:1:0.05:0.06. [b] Yield
determined by column chromatography. [c] Determined by chiral HPLC
analysis of the desilylated compound. [d] 1 mol% catalyst. Ts=toluene-
4-sulfonyl, cod=1,5-cyclooctadiene, L=ligand.
1,2-dichloroethane (DCE) at 708C in the presence of a
rhodium catalyst generated in situ from 5 mol% [Rh-
(cod)2]BF4 and 6 mol% (R)-SDP. Substrate 1a was rapidly
consumed within two hours and the silylcyclization product
3aa was produced in 60% yield with 98% ee (Table 1,
entry 1). In other solvents, such as 1,2-dimethoxyethane,
THF, dioxane, and toluene, the reaction gave the desired
product in very low yields. Varying the reaction temperature
in the range from room temperature to 908C had only a small
effect on the enantioselectivity of the reaction, although the
reaction at room temperature took 24 h and the yield was
lowered to only 43% (Table 1, entry 2). The best result in
terms of enantioselectivity was achieved at 708C. The catalyst
loading experiments demonstrated that the reaction could be
performed with 1 mol% catalyst without obvious loss of
enantioselectivity or yield (Table 1, entry 5).
[*] Dr. B.-M. Fan, Prof. J.-H. Xie, S. Li, Prof. L.-X. Wang, Prof. Q.-L. Zhou
State Key Laboratory and Institute of Elemento-organic Chemistry
Nankai University
Tianjin 300071 (P.R. China)
Fax: (+86)22-2350-6177
E-mail: qlzhou@nankai.edu.cn
[**] We thank the National Natural Science Foundation of China and the
Ministry of Education of China for financial support. Throughout
this Communication hydrosilylation/cyclization will be written in the
short form silylcyclization.
The effect of substituents on the SDP ligand was also
studied systematically. Introduction of 4-methyl (Tol-SDP)
Supporting Information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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and 4-methoxy (An-SDP) groups onto the P-phenyl rings of
alkyl groups are used. For example, in the reaction with
HSiiPr3 (2d) only a trace amount of silylcyclization product
was obtained (Table 2, entry 4). The use of 5 equivalents of
silane is necessary to limit side reactions such as the
dimerization of 1,6-enynes.
A variety of 1,6-enynes (1) can be silylcyclized by the
catalyst Rh/(R)-SDP to form the silylalkylidene cyclopentane
and pyrrolidine derivatives 3 in excellent enantioselectivities
(Scheme 1). The N-linked 1,6-enynes 1a–e, which have
SDP significantly increased the reaction rate, thus allowing a
shortening of the reaction time to 0.5 h (Table 1, entries 6 and
7). However, the enantioselectivities of the reactions were
reduced to 87% and 89% ee, respectively, with Tol-SDP and
Xyl-SDP as ligands (Table 1, entries 6 and 8, respectively).
Some commercially available chelating diphosphine
ligands were also tested in this reaction. The ligands 2,2’-
bis(diphenylphosphino)-1,1’-binaphthyl (BINAP) and (5,6),-
(5’,6’)-bis(ethylenedioxy)-2,2’-bis(diphenylphosphino)-1,1’-
biphenyl (SYNPHOS) gave lower enantioselectivities than
the SDP ligands, and the ligand 1-[2-(diphenylphosphino)-
ferrocenyl]ethyldicyclohexylphosphine (JOSIPHOS) gave
both low enantioselectivity and
a poor yield (18%,
38% ee). The ligand 1,2-bis(2,5-dimethylphospholano)ben-
zene (Me-DuPHOS) was found to be completely inert in the
reaction, providing none of the desired silylcyclization
product. These results apparently indicate that the rigid
spiro backbone of the SDP ligands is the key factor for
achieving high enantioselectivity in the silylcyclization of 1,6-
enynes.
A series of silane reagents 2 were compared in the
silylcyclization reaction of 1,6-enyne 1a under the optimized
reaction conditions. The results summarized in Table 2 show
Scheme 1. The asymmetric rhodium-catalyzed silylcyclization of
1,6-enynes. For R, R’, and X, see Table 2.
Table 2: Asymmetric silylcyclization of 1,6-enynes 1 with silanes 2
catalyzed by the rhodium(I) complex of SDP.[a]
different protecting groups on the nitrogen atom, were
silylcyclized in moderate to good yields with 92–98% ee,
thus showing that sulfonyl groups are suitable protecting
groups for N-linked 1,6-enyne substrates, with the tosyl group
being the best choice (Table 2, entries 8–12). To extend the
scope of substrates in this silylcyclization reaction, carbon-
linked 1,6-enynes (1 f–j) were also studied. They all reacted
smoothly to produce the corresponding silylcyclization com-
pounds in reasonable yields and excellent enantioselectivities
(Table 2, entries 13–17). The highest enantioselectivity
(99.5% ee) was achieved in the silylcyclization of 4,4-bis-
(cyano)hept-1-en-6-yne (1j) with HSiEt3 (Table 2, entry 17).
However, when 1,6-enyne substrates having a phenyl group
attached to the alkyne or alkene terminus were silylcyclized,
only trace amounts of the desired products were obtained.
The silyl groups in the silylcyclization products can be
easily converted into other functional groups by reported
methods,[11] which increases the impact of this asymmetric
silylcyclization reaction of 1,6-enynes on the synthesis of
optically active compounds containing a cyclopentane or
pyrrolidine structure. As shown in Scheme 2, the silylalkyli-
dene pyrrolidine derivative 3eh can be desilylated by treat-
ment with 2 equivalents of AgF in aqueous MeOH/THF at
room temperature for three hours to afford compound 4e in
92% yield.[11c] Pd-catalyzed, the silylcyclization product 3ah
can react with iodobenzene to form phenylated compound 5
in 84% yield.[11b] The optical purities of the silylalkylidene
pyrrolidines were completely retained in these two reactions.
To explain the stereoselectivity of the spiro catalyst in the
silylcyclization, a transition-state (TS) model is proposed in
Entry
1
X[b]
R’
2
Silane
3
Yield [%] ee [%][c]
1
2
3
4
5
6
7
8
1a TsN
1a TsN
1a TsN
1a TsN
1a TsN
1a TsN
1a TsN
1a TsN
1b PhSO2N
1c NsN
1d MsN
1e TsN
H
H
H
H
H
H
H
H
H
H
H
2a HSiEt3 3aa 60
2b HSiMeEt2 3ab 75
2c HSinPr3
2d HSiiPr3
2e HSiMe2Ph 3ae 72
2f HSiMePh2 3af 70
2g HSi(OMe)3 3ag 67
2h HSi(OEt)3 3ah 75
2a HSiEt3
2a HSiEt3
2a HSiEt3
98
98
99
–
3ac 41
3ad trace
93
89
96
98
92
95
92
92
96
95
94
95
99.5
9
3ba 59
3ca[d] 67
3da 56
10
11
12
13
14
15
16
17
Me 2h HSi(OEt)3 3eh 93
2h HSi(OEt)3 3 fh 67
1f (EtO2C)2C
H
1g (EtO2C)2C Me 2a HSiEt3
1h (MeO2C)2C 2a HSiEt3
1i (MeO2C)2C Me 2a HSiEt3
1j (NC)2C 2a HSiEt3
3ga 48
3ha 72
3ia
3ja
H
50
50
H
[a] Reaction conditions: see Table 1, entry 1. [b] Ns: nitrobenzene-4-
sulfonyl, Ms: methanesulfonyl. [c] Determined by chiral GC or HPLC (see
Supporting Infomation). [d] (S)-3ca, determined by X-ray crystallography
(see Supporting Information).
that both trialkylsilanes (HSiR3) and trialkoxysilanes
(HSi(OR)3) can serve as the silane reagents, although the
silanes with phenyl groups give slightly lower enantioselec-
tivities (Table 2, entries 5 and 6). The yield of silylcyclization
product decreases dramatically when silanes containing bulky
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cyclic compounds after subsequent appropriate transforma-
tions.
Received: August 30, 2006
Revised: October 18, 2006
Published online: January 4, 2007
Keywords: asymmetric catalysis · enynes ·
.
hydrosilylation/cyclization · P ligands · rhodium
Scheme 2. Examples for the conversion of the silyl groups of the
silylcyclization products. TBAF=tetrabutylammonium fluoride.
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reactions.
Figure 1. In TS-1 the bulky silyl groupis located in a relatively
open area; this orientation favors the formation of the S
product, which is consistent with the absolute configuration of
(S)-3ca determined by X-ray analysis.
In conclusion, we have developed an efficient catalyst,
namely the rhodium complex of spiro diphosphine SDP, for
the asymmetric silylcyclization of 1,6-enynes. This highly
enantioselective reaction provides a facile access to optically
active silylalkylidene cyclopentane and pyrrolidine deriva-
tives, along with other functionalized carbocyclic and hetero-
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