Regioselective oxidative cation-olefin cyclization of poly-enes: Catalyst turnover via hydride abstraction

Article abstract of DOI:10.1021/ja073573l

Electrophilic P₂Pt²⁺ complexes are shown to catalyze the regio- and diastereoselective oxidative cascade cyclization of poly-enes. The reactions are stereospecific with respect to the initiating alkenes geometry and suggest an all-chair, semiconcerted transition structure. Catalyst turnover after cyclization apparently occurs via β-hydride elimination and subsequent hydride abstraction (from P₂Pt-H⁺) by added Trityl cation (in the form of trityl methyl ether or a resin version thereof) to regenerate the active P₂Pt₂₊ state. One intriguing possibility is that the high regioselectivity observed in the β-H elimination is due to a regio-defining β-agostic resting state. Copyright

Full text of DOI:10.1021/ja073573l

Published on Web 09/13/2007
Regioselective Oxidative Cation-Olefin Cyclization of Poly-enes: Catalyst
Turnover via Hydride Abstraction
Charles A. Mullen and Michel R. Gagne´*
Department of Chemistry, UniVersity of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290
Received May 18, 2007; E-mail: mgagne@unc.edu
Biomimetic polyolefin cascade reactions are among the most
challenging problems in reaction design,1 and since few catalysts
initiate ligand controlled cation-olefin cyclizations,2,3 we became
interested in developing one around the reactive core of electrophilic
Pd(II) and Pt(II).4 In contrast to H+, Br+, and other carbophilic
metals, Pd(II) and Pt(II) preferentially coordinate and activate the
less substituted alkene,5 which directs the point of coordination/
activation to the terminus in substrates such as 1.
“reoxidation”) was not well precedented,4 in contrast to ubiquitous
Pd analogues. One differentiating feature is that these dicationic
Pt catalysts lack the coordinating X- ligands (Cl-, -OAc, etc.),
which are key to facilitating metal reoxidation.9 This makes
traditional M(0) to M(II) oxidizing reagents such as benzoquinone,
O2, CuCl2, etc. ineffective for this system.10
The hydride abstracting agent (triphenylcarbenium)BF4 (TrBF4),
however, was found to efficiently convert the key intermediate back
to the (dppe)Pt2+ state for reinitiating catalytic turnover.11 Thus,
10 mol % (dppe)Pt2+ and stoichiometric TrBF4 combined with a
weak base (Ph2NH) serves to absorb the H- and H+ generated from
the heterolytic loss of H2 on conversion of 1 to 2. A more
convenient Tr+ source was trityl methyl ether, which generates Tr+
and MeOH on reacting with the H+ expelled on cyclization. This
approach keeps Tr+ concentrations low by only releasing the amount
needed for each turn of the cycle, reducing the probability of Tr+
mediated side reactions while also removing the need for exogenous
amine base.
As outlined in eq 1 (PhCN)2PdCl2 in combination with benzo-
quinone (BQ) effectively catalyzes the oxidative cyclization of poly-
enes.6 Although the diastereoselectivity was high, this methodolo-
gy’s regioselectivity was problematic owing to alkene isomerization
after â-hydride elimination. Additionally, all attempts to develop
an asymmetric variant of this catalyst failed as added ligands
inhibited the catalysis. We7 and others5c,d have also reported that
(tris-phosphine)Pt-dications efficiently initiate cation-olefin trans-
formations that mediate the cycloisomerization of dienes into
bicyclopropanes.7a-c However, with substrates such as 1, which
contain an internal cation trap, the resulting cyclic Pt-alkyl is
resistant to â-H elimination (no open cis coordination sites to allow
for hydride migration), and the reaction does not turn over. The
cyclized product is recoverable, however, by reductive cleavage
using NaBH4.7d
Additional optimization led to a polystyrene resin bound trityl
methyl ether that enables simple removal of excess TrOMe and
TrH.12 No loss in yield was observed on using this solid-phase
reoxidant. A screen of readily available diphosphines (not shown)
indicated that dppe provided the most high-yielding catalyst, and
nitroethane was the ideal solvent.
These optimum conditions were applied to a variety of diene-
and triene-ol substrates (Table 1).13 The reactions typically went
to completion with 10 mol % 3 and consistently provided high
regioselectivities and only trans ring junctions (predicted by the
Stork-Eschenmoser postulate14 for E internal olefins). In addition
to terminal alkenes, 1,2-disubstituted termini were also tolerated
(entries 3-5, 7, 8). These reactions were stereospecific as the E
and Z isomers led to epimeric products at C-4 and suggested
chairlike transition states tolerant of unfavorable developing 1,3-
diaxial interactions for the Z substrates (Scheme 1). Terminal
trisubstitution was not tolerated (entry 9).
A proposed catalytic cycle is shown in Scheme 2. Coordination
and activation of the less substituted CdC double bond by P2Pt2+
at the terminus of the substrate initiates the cascade cyclization.
The trapping of the final cation by the alcohol generates acid which
cleaves TrOMe into trityl cation and methanol. The intermediate
P2Pt-alkyl cation I has been observed as the resting state of this
catalytic cycle by 31P NMR. The fourth coordination site in I is
Rationalizing that an open cis site would enable â-H elimination
from a putative alkyl intermediate, we initiated an examination of
P2Pt-dication catalysts for the oxidative cyclization of 1. These
studies led to a novel catalyst system for the regioselectiVe oxidative
cyclization of poly-enols that additionally utilizes trityl cation to
achieve catalyst turnover.
The combination of [(dppe)Pt][BF4]2 (3),8 1, and a weak base at
room temperature generated 2 as a single diastereomer and
regioisomer (eq 3). This product reasonably results from a regio-
selectiVe â-hydride elimination of an intermediate (P2)Pt-cyclo-
alkyl cation. The contrast to Pd-based methods is striking (cf. eq
1). We presume a [(dppe)Pt(H)][BF4] byproduct but it appears to
decompose.
The cyclization/â-elimination step of a putative mechanism for
catalysis was thus realized; however, the conversion of “P2Pt-
H+” to the active dication for reinitiating the cycle (catalyst
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J. AM. CHEM. SOC. 2007, 129, 11880-11881
10.1021/ja073573l CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
a
Table 1. Polycyclizations Catalyzed by (dppe)PtI2/AgBF4
Scheme 2. Proposed Catalytic Cycle
tion processes by a Tr+ mediated hydride abstraction pathway.
Studies to further understand the mechanism of this turnover step
are underway.
Acknowledgment. We thank the National Institutes of Health,
General Medicine for generous support (Grant GM-60578).
Supporting Information Available: Characterization details for
all new compounds, and representative synthetic procedures. This
material is available free of charge via the Internet at http://pubs.acs.org.
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