Catalytic platinum-initiated cation-olefin reactions with alkene terminating groups

Article abstract of DOI:10.1039/c3cc41699b

A series of phosphine-Pt²⁺-catalysts is reported, which enable the oxidative cascade cyclization of poly-alkene substrates. When the terminus is appropriately arranged and a catalyst reoxidation mediator is included, several polycyclic all carbon skeletons can be obtained. In one example, a chiral P₂Pt⁺² catalyst provides up to 79% ee. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3cc41699b

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Catalytic platinum-initiated cation-olefin reactions
with alkene terminating groups†
Cite this: Chem. Commun., 2013,
49, 5046
a
a
b
a
´
Joseph G. Sokol, Nikki A. Cochrane, Jennifer J. Becker and Michel R. Gagne*
Received 6th March 2013,
Accepted 16th April 2013
DOI: 10.1039/c3cc41699b
www.rsc.org/chemcomm
A series of phosphine–Pt2+-catalysts is reported, which enable the protic termini (e.g. eqn (2)). In this contribution we extend these
oxidative cascade cyclization of poly-alkene substrates. When the initial observations, which were stoichiometric in Pt(II), to ligand–
terminus is appropriately arranged and a catalyst reoxidation mediator metal combinations that are amenable to catalysis and with chiral
is included, several polycyclic all carbon skeletons can be obtained. ligand variants, asymmetric catalysis.
In one example, a chiral P2Pt+2 catalyst provides up to 79% ee.
The cation-olefin cascade cyclization of polyenes with a terminating
(2)
alkene are considerably more difficult than the analogous cycliza-
tion containing a protic terminus (OH, NH, etc.),1 e.g. eqn (1).2
Terminating group effects on cyclization efficiency have been long
known and pioneers like Johnson,3 van Tamelen4 and Corey5 used
Our earliest studies sought to simply apply the conditions
optimized for reactions like eqn (1), but these led to poor rates
and conversions that eventually ceased prior to complete con-
sumption of starting material. Based on unpublished observa-
tions that show slow hydride abstraction to be the cause of
catalyst deactivation, optimization efforts sought to improve
the hydride abstraction step of the proposed mechanism by the
addition of Ph3C+ (Tr+) to the catalyst formulation (Scheme 1).
Under these conditions improved conversions were possible.
These conditions were utilized to search for beneficial ligand
effects. A screen of common diphosphine ligands showed
that BINAP provides a catalyst capable of generating 81% 2 at
these effects to benefit in the development of increasingly efficient
synthetic methodologies.6 Thus far, catalytic methodologies, espe-
cially those able to exercise absolute stereocontrol have been unable
to overcome the challenge of a simple alkene terminating group.5,7
H-bond activation of terminating OH groups by a base leads to a
nearly barrierless cascade (once in the correct conformation), which
additionally benefits from an enhanced thermodynamic driving
force.8 Since alkene termini do not become acidic until the cation is
nearly fully formed, H-bond assistance is lost in these cases and
higher energy intermediates are required with a concominant
decrease in cyclization rate. Enzymatic cyclizations can overcome
these inherent features by the strategic positioning of bases or
arenes for stabilizing cation-p interactions,9 but fully synthetic
versions must rely on other means.
(1)
We have recently reported that electrophilic (triphos)Pt-dications
can indeed initiate the cation-olefin cascade cyclization of all-alkene
substrates,10 though rates suffered considerably versus analogs with
a Department of Chemistry, University of North Carolina at Chapel Hill,
Chapel Hill, North Carolina 27599-3290, USA. E-mail: mgagne@unc.edu
b U.S. Army Research Office, P.O. Box 23322, Research Triangle Park,
North Carolina 27709, USA
† Electronic supplementary information (ESI) available: Synthesis and characteri-
zation of all compounds. See DOI: 10.1039/c3cc41699b
Scheme 1 Proposed mechanism.
c
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Table 1 Screen of hydride abstraction agents
Table 2 Polyene cyclizations catalyzed by (BINAP)Pt2+
Conversionc
Entrya Substrate
Product
Timeb (h) (isolated yield)
1
36
89d (14)
Entry
Hydride abstractor
2a (%)
1
2
3
4
5
6
7
8
200% TrOMe
300% TrOMe resin
200% 2(4-Meo)TrOMe
300% (4-MeO)TrOMe resin
200% TrOMe, 10% TrBF4
160% TrOMe, 20% TrBF4
100% TrOMe, 50% TrBF4
160% (MeO)2CH2, 10% [Ph2NH2][BF4]
17
14
7
2
3
36
16
90d (19)
33e (9)
8
44
65
90b
18
a
Determined by GC analysis. Remainder is unreacted 1. b 15% Isolated yield.
90% conversion; the mass balance were minor amounts of
unidentified isomeric products.
4
5
9 R = H
11 R = OMe
10
12
24
8
50 f (5)
55 f (5)
A second round of optimization on the BINAP-based cata-
lyst, paying particular attention to the seemingly key hydride
abstraction step was undertaken. In addition to TrOMe, the
4-methoxy variant, resin based versions of both and recently
reported acetal-based variants were tested.11 While dimethoxy
methane (and benzaldehyde) function well with protic termi-
nators, they led to reaction rates that were half that of TrOMe.
The use of TrOMe plus an equimolar quantity (to Pt) of TrBF4
ensured that the putative P2Pt–H+ intermediate reacted with at
least a 2-fold excess of Tr+. More than any other modification
of the reaction conditions, extra Tr+ was most beneficial.
Increasing TrBF4 up to a 5-fold excess (vs. Pt) was optimum
and 100% conversion of 1 was possible (Table 1).12
With a set of reaction conditions capable of efficiently con-
verting 1 to 2 (90%) in hand, a survey of alternative poly-ene
structures was undertaken (Table 2). Tetra-ene 3 efficiently
generated a single stereoisomer of 4 as the predominant
product of the oxidative cyclization (entry 1). Previous studies
have shown7 that the nucleophilicity of the terminating
alkene13 is a good predictor of the reaction time. Poly-ene
substrates with more nucleophilic terminating alkenes were
thus tested, though their cyclizations met with mixed success.
Some cyclized effectively (e.g. entry 2) while others displayed
more complex behavior. The styrene terminated 5 proved to be
an excellent substrate, providing a product whose mass balance
was 90% bicyclic diene 6. In contrast, the para-methoxy
substituted variant, 15, preferentially isomerizes to the tri-
substituted (and unreactive) alkene 16 (eqn (3)).
6
16
32g (4)
a
Reaction conditions: 100 mmol substrate, 10 mmol (BINAP)PtI2, 22.5 mmol
AgBF4, 30 mmol NCC6F5, 30 mmol Ph2NH, 100 mmol TrOMe, 50 mmol TrBF4,
and 0.6 mL EtNO2. Reaction time determined by consumption of starting
material (GC analysis). GC conversions report mass balance of desired
product relative to all other isomers and starting material. Spectroscopically
pure (Z95%) products could be obtained, though difficulties in hydro-
carbon separation considerably lowered the isolated yields. Mass balance
composed of a single undetermined product isomer. Mass balance
b
c
d
e
composed of 3 products from side reactivity between starting material
and Tr+ in a 2.1: 1 : 1.9 ratio. Mass balance composed of corresponding
f
g
naphthyl product 15/16. Mass balance composed of 5 monocyclized
product isomers in a 1.3: 2.1: 1.3: 1 : 2.2 ratio.
Scheme 2 Side reactions of dihydronaphthyl substrate and product.
(3)
rearrangement under the acidic conditions. This rearrangement
could be accelerated by the deliberate addition of acid (MeSO3H).
Aryl terminating groups have provided mixed success with
The low selectivities for the dihydronaphthyl substrates 9 other cyclization techniques.14 In the present case, 13 provided
and 11 are due to a series of side reactions (Scheme 2), including numerous side products, despite having the stoichiometric
direct oxidization by Tr+/TrOMe of the dihydro naphthyl to a cyclizations with (PPP)Pt+2 being selective for a single product.15
naphthyl analog, which was surprisingly unreactive to follow
The clean conversion of 5 to diene 6 suggests that the
up cyclization. Compounds 10 and 12 were also prone to putative carbenium ion intermediate A may generate the product
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terminating groups. Proof-of-principle enantioselective results
are also reported.
Notes and references
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Scheme 3 Cation intermediate for the conversion of 5 to 6.
Table 3 Effect of ligand on enantioselectivity
´
2 J. H. Koh and M. R. Gagne, Angew. Chem., Int. Ed., 2004, 43,
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Entry
Ligand
Conversiona (%)
% eeb
´
6 M. Kotora, F. Hessler and B. Eignerova, Eur. J. Org. Chem., 2012,
1c
2
3
(R)-xylyl-PHANEPHOS
(R)-xylyl-MeO-BINAP
(R)-xylyl-BINAP
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80
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90
79
68
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44
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4
(R)-SEGPHOS
˜
a
b
Mass balance composed of unreacted starting material. Determined
c
˜
by chiral GC. The absolute configuration of 2 is predicted to be as
shown by analogy to previously reported work.18
8 T. Nowroozi-Isfahani, D. G. Musaev, K. Morokuma and M. R.
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´
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control of a P2Pt+2-catalyst suggests the reasonableness of
enantioselective variants. As shown in Table 3, the optimum
conditions could be ported to catalysts carrying chiral diphos-
phine ligands. As before,18 the xylyl-PHANEPHOS derived
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16 DFT B3LYP/6-31G* calculations on the deplatinated analogs,
though xylyl-BINAP gave a reasonable compromise between
conversion and % ee.
As described herein, the significant challenge of an ionic
catalyst-controlled cascade-cyclization of poly-enes can at least
partially be solved using P2Pt+2 catalysts. Key to the method-
ology development has been the realization that fast hydride
abstraction from a key Pt–H intermediate is key to catalytic
efficiency. To our knowledge these represent a first for a
catalytic cascade cyclization of polyenes containing alkene
MacSpartan 2008 calculations; energies were uncorrected.
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´
18 C. A. Mullen, A. N. Campbell and M. R. Gagne, Angew. Chem.,
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c
5048 Chem. Commun., 2013, 49, 5046--5048
This journal is The Royal Society of Chemistry 2013