Asymmetric Synthesis and Application of Chiral Spirosilabiindanes

Article abstract of DOI:10.1002/anie.202002289

Reported here is the development of a class of chiral spirosilabiindane scaffolds by Rh-catalyzed asymmetric double hydrosilation, for the first time. Enantiopure SPSiOL (spirosilabiindane diol), a new type of chiral building block for the preparation of various chiral ligands and catalysts, was readily prepared on greater than 10 gram scale using this protocol. The potential of this new spirosilabiindane scaffold in asymmetric catalysis was preliminarily demonstrated by development of the corresponding monodentate phosphoramidite ligands (SPSiPhos), which were used in both a Rh-catalyzed hydrogenation and a Pd-catalyzed intramolecular carboamination.

Full text of DOI:10.1002/anie.202002289

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Accepted Article
Title: Asymmetric Synthesis and Application of Chiral
Spirosilabiindanes
Authors: Xin Chang, Pei-Long Ma, Hong-Chao Chen, Chuan-Ying Li,
and Peng Wang
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10.1002/anie.202002289
Angewandte Chemie International Edition
COMMUNICATION
Asymmetric Synthesis and Application of Chiral
Spirosilabiindanes
Xin Chang,[a,c] Pei-Long Ma,[a] Hong-Chao Chen, Chuan-Ying Li,*[c] and Peng Wang*[a,b]
Dedicated to the 70th anniversary of Shanghai Institute of Organic Chemistry
[a]
Miss. X. Chang, Mr. P.-L. Ma, Mr. H.-C. Chen, Prof. Dr. P. Wang
State key laboratory of organometallic chemistry, Center for excellence in molecular synthesis
Shanghai Institute of Organic Chemistry, CAS
345 Lingling Road, Shanghai 200032, P. R. China
E-mail: pengwang@sioc.ac.cn
[b]
[c]
Prof. Dr. P. Wang
CAS Key Laboratory of Energy Regulation Materials
Shanghai Institute of Organic Chemistry, CAS
345 Lingling Road, Shanghai 200032, P. R. China
Miss X. Chang, Prof. Dr. C.-Y. Li
Department of Chemistry
Zhejiang Sci-Tech University
Xiasha West Higher Education District, Hangzhou 310018, P.R. China
E-mail: licy@zstu.edu.cn
Supporting information for this article is given via a link at the end of the document.
Abstract: Herein, we report the development of a class of chiral
spirosilabiindane scaffolds via Rh-catalyzed asymmetric double
hydrosilation for the first time. Enantiopure SPSiOL (spirosilabiindane
diol), a new type of chiral building block for preparation of various
chiral ligands and catalysts, could be readily prepared on >10-gram
scale using this protocol. The potential of this new spirosilabiindane
scaffold in asymmetric catalysis was preliminarily demonstrated by
development of corresponding monodentate phosphoramidite ligands
(SPSiPhos), and by applying those ligands in a Rh-catalyzed
hydrogenation and a Pd-catalyzed intramolecular carboamination.
Axially chiral spirocyclic scaffolds have been seem as appealing
chiral blocks which are widely found in ligands and
organocatalysts.[1] Among those spirocyclic scaffolds, 1,1’-
spirobiindane derivatives present elegant stereocontrol and high
efficiencies in a wide range of asymmetric transformations,[1-3] and
become one of the privileged chiral structures thanks to seminal
contribution by Zhou and coworkers.[3] Accordingly, recent
developments are mainly focused on the practical preparation of
such scaffold and its analogues.[4,5] In addition, few elegant
examples regarding the modification of the backbone by oxygen
started to emerge in the literatures.[6] However, major progresses
are still limited to carbon-center spirocyclic scaffolds,
a
conformationally more constrained Si-center spirosilanes based
ligand design, to the best of our knowledge, has not been reported
to date. The longer C–Si bond (C–Si vs C–C: ca 1.87 Å vs ca.
1.53 Å),[7c] bigger atomic radius (Si vs C: 111 pm vs 67 pm),
Scheme 1. Asymmetric Synthesis of Spirosilabiindanes.
first asymmetric synthesis of axially chiral thiophene-containing
spirosilane via Rh-catalyzed intramolecular hydrosilation using
TBDM-SILOP as ligand (Scheme 1b).[8b] Kuninobu and Takai
demonstrated the asymmetric synthesis of spirosilabifluorene
derivatives via dehydrogenative silylation approach with up to 81%
ee.[8c] Later, the sole example for the asymmetric synthesis of
spirosilabiindane derivative in 75% yield with 40% ee using the
same approach was demonstrated by Murai and Takai.[8a] Herein,
vertical configuration of Si-spirocycle[7] might lead to
a
constrained structure with different bite angle in comparison to C-
center spirobiindane scaffold (Scheme 1a). Those unique
properties could provide tremendous opportunities for new
ligands and catalysts development.
Despite of the conspicuously potential of chiral spirosilabiindane
scaffold, highly enantioselective synthesis of this chiral motif is
barely reported.[8] In 1996, Tamao and coworkers reported the
1
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10.1002/anie.202002289
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we reported the rational design, synthesis, and application of Si-
center spirosilabiindane scaffold. Highly enantioselective
synthesis of spirosilabiindanes has been demonstrated for the
first time via Rh-catalyzed asymmetric double hydrosilation
employing (R, R)-Et-DuPhos or (R)-QuinoxP as chiral ligand. In
addition, SPSiOL (spirosilabiindane diol) can be easily accessed
using our methodology on >10-gram scale, which could be readily
transformed to a broad range of chiral ligands. The versatility of
this new chiral scaffold was demonstrated by application of its
derived phosphoramidite ligands in asymmetric catalysis.
presents the highest diastereoselectivity and enantioselectivity
(98% ee, >96/4 dr) with 99% yield. Notably, a couple of
enantiomers could be selectively obtained by choosing (R)-
QuinoxP or (R, R)-Et-DuPhos as chiral ligand, respectively. The
absolute stereochemistry of spirosilabiindanes was determined
by analogy to that of 2c and 2q, which were determined by X-ray
crystallographic analysis (Table 2). The configuration of the minor
diastereomer was determined by analyzing single-crystal X-ray
crystallographic of the diastereomer of 2q (see 2q’ in Supporting
Information).
Table 1. Ligand Evaluation for Asymmetric Synthesis of Chiral Spirosilabiindane
Table 2. Rh-Catalyzed Asymmetric Synthesis of Spirosilabiindanes.[a,b]
Scaffold.[a,b]
.
[a] Reaction conditions: 1 (0.1 mmol), [Rh(1,5-hexadiene)Cl]2 (2.0 mol %),
Phosphine Ligand (4.0 mol %), DCM (1.0 mL), rt, N2, 12 h. [b] Isolated yield; the
enantiomeric excess ratio (ee) was determined by chiral HPLC; diastereomeric
ratio (dr) was determined by crude 1H NMR.
We commenced the asymmetric synthesis of spirosilabiindanes
by
bis(alkenyl)dihydrosilanes 1. Starting from commercially available
2-bromobenzaldehyde or 2-bromophenone derivatives,
developing
a
synthetic
route
to
access
the
bis(alkenyl)dihydrosilanes 1 can be readily prepared in two steps
in high yields (see Supporting Information). Employing 1a as
model substrate, we initiated the investigation of asymmetric
cyclization in the presence of [Rh(1,5-hexadiene)Cl]2 (2.0 mol %),
and (R, R)-DIOP (4.0 mol %) in dichloromethane under nitrogen.
Although excellent chiral induction was obtained for the synthesis
of thiophene-containing spirosilane by Tamao using (R, R)-DIOP
as ligand (83% ee)[8b], the desired spirosilabiindane 2a could only
be obtained with 37% ee and 94:6 dr in 98% total yield. Following
this lead, a series of chiral biphosphine ligands were evaluated,
as depicted in Table 1. The reaction proceeded in high yield using
(S)-BINAP (L2) or (R, R)-Ph-BPE (L3) as ligand but barely chiral
induction and moderate diastereoselectivity. (R, S)-Josiphos (L4)
gave 2a in 87% ee and 94:6 dr without the loss of the efficiency,
while (R)-BDPP (L5) provided 97:3 dr and 73% ee. Notably, a
significant improvement of the enantiocontrol was obtained (99%
ee, 95:5 dr, 98% yield) when (R)-QuinoxP was employed for this
intramolecular double hydrosilation. In addition, (R, R)-DuPhos
(L7-9) also promoted this process to afford the desired spirosilane.
The substituent on phosphine of the DuPhos scaffold has a
significant impact on the stereocontrol, in which (R, R)-Et-DuPhos
[a] Reaction conditions: 1 (0.1 mmol), [Rh(1,5-hexadiene)Cl]2 (2.0 mol %), (R,
R)-Et-DuPhos, DCM (1.0 mL), rt, N2, 12 h. [b] bIsolated yield; the enantiomeric
excess ratio (ee) was determined by chiral HPLC; diastereomeric ratio (dr) was
determined by crude 1H NMR. [c] (R)-QuinoxP (4.0 mol %).
Under the optimal conditions, the generality of this asymmetric
Rh-catalyzed double hydrosilation was evaluated. In general, this
reaction was applicable to synthesize a wide range of chiral
spirosilabiindanes, affording the desired products in excellent
yields (84–99%), dr (91:9 – > 96:4), and excellent ee values (90–
99%). Replacement of methyl on alkene with H (2d) and Et (2b)
didn’t significantly affect the efficiency and chiral induction under
2
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10.1002/anie.202002289
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COMMUNICATION
the standard conditions. Although phenyl substituted alkenes was
inert in the presence of (R, R)-Et-DuPhos probably due to steric
hindrance, (R)-QuinoxP provided the corresponding Si-spirocycle
2c in 88% yield with 99% ee and >96:4 dr. Both electron-rich and
electron-deficient substitutes on various positions of aryl group
(2d-o) are tolerated with excellent outputs, in which (R)-QuinoxP
normally gave better chiral induction for electron-deficient
substrates (2g, 2h, 2l). Most importantly, substrates bearing an
ortho-methoxyl group, which could convert to SPSiOL upon
demethylation, are also compatible with this procedure, yielding
the targeted spirosilabiindanes in high yields and ees (2p-r).
The application of SPSiPhos in asymmetric catalysis was further
demonstrated. Comparable excellent enantioselectivities were
obtained with SPSiPhos for Rh-catalyzed asymmetric
hydrogenation
of
methyl
(Z)-2-acetamidocinnamate
in
comparison to SIPHOS (99.8% ee vs 97% ee).[9] Notably,
significant enhancement of the reactivity with excellent chiral
induction was observed, when we applied our SPSiPhos in Pd-
catalyzed intramolecular carboamination.[10] The use of SPSiPhos
allows this carboamination proceeded at room temperature,
whereas high temperature was required in the presence of C-
centered spirocyclic phosphoramidite. The excellent chiral
induction along with the potential for enhancing the reactivities
make the newly designed SPSiOL a charming chiral scaffold.
Scheme 2. Gram-Scale Synthesis of SPSiOL.
The practicality and scalability of this protocol were demonstrated
by the synthesis of 2p-r on gram scale using 0.5 mol % Rh
catalyst, providing corresponding Si-spirocycles in 90-96% yield
without the loss of the stereoselectivity. Noteworthy, enantiopure
2p-r were obtained in 84-89% yield upon crystallization. SPSiOLs,
a new type of chiral building block for synthesis of various chiral
ligands and catalysts, were produced on gram-scale in 92-97%
yields after demethylation under mild conditions (Scheme 2).
Scheme 4. Applications of SPSiOL-Based Ligands.
In summary, the highly enantioselective synthesis and
applications of spirosilabiindanes have been demonstrated.
Preliminary study indicates that spirosilabiindane backbone has
the potential in providing outstanding chiral induction, and
enhancing the reactivities. Further applications of our
spirosilabiindane scaffold in chiral ligand and catalyst
development, and exploration of those SPSiOL-based ligands
and catalysts in asymmetric catalysis are underway in our
laboratory.
Scheme 3. Synthesis of Spiro-Si based Phosphoramidites.
Next,
a
series of SPSiOL-based chiral monodentate
phosphoramidites (SPSiPhos) were produced starting from the
enantiopure SPSiOLs. As shown in Scheme 3, ligands of this
class bearing a dimethylamino (4a-c), diethylamino (4d-f),
diisopropylamino (4g-i), morpholino (4j-l), or a chiral amino group
(4m-o), were obtained in good to excellent yields. The three
dimensions structure of SPSiOL 3a and SPSiPhos 4g were
elucidated by X-ray crystallography (See Supporting Information).
In comparison to C-centered SPINOL[5c], SPSiOL 3a has a bigger
dihedral angel between two phenyl rings (92.2o vs 64.2o) and a
longer O–O distance (5.155 Å vs 3.439 Å) probably due to the
hybridization of Si and the longer C–Si bond (CAr–Si vs CAr–C:
1.86 Å vs 1.52 Å; Csp3–Si vs Csp3–C: 1.88 Å vs 1.56 Å). The
structurally remarkable difference could provide a new platform
for ligand and organocatalyst developments.
Acknowledgements
We gratefully acknowledge Shanghai Institute of Organic
Chemistry, State Key Laboratory of Organometallic Chemistry,
National Natural Science Foundation of China (21821002) for
financial support.
Keywords: spirosilabiindane • hydrosilation • asymmetric •
SPSiOL • SPSiPhos
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4
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Entry for the Table of Contents
Herein, we report the rational design, asymmetric synthesis, and application of chiral spirosilabiindane scaffolds. Highly
enantioselective synthesis of spirosilabiindanes has been demonstrated for the first time via Rh-catalyzed double hydrosilation. The
versatility of this new chiral scaffold was demonstrated by gram-scale synthesis of SPSiOL, and application of its derived
phosphoramidite ligands in asymmetric catalysis.
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