PdII- and PtII-mediated polycyclization reactions of 1,5- and 1,6-bienes: Evidence in support of carbocation intermediates

Article abstract of DOI:10.1002/anie.200453913

Pincer-ligated Pd^II and Pt^II dicationic complexes efficiently generate cations from 1,5- and 1,6-dienes. These transient cations can be selectively trapped with heteroatoms, alkenes, and through pinacol rearrangements. For example, trienyl-phenol 1 is converted into tetracyclic 2 in high yield and diastereomeric ratio (see scheme).

Full text of DOI:10.1002/anie.200453913

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Chemie
Cyclizations
nated ethylene was proposed, with turnover by a sequence of
1,2-hydride shifts. Most importantly, b-hydride elimination
did not occur, since no open cis coordination sites were
available, and this suggests that this complex might be capable
of initiating cation formation while preserving the stereo-
PdII- and PtII-Mediated Polycyclization Reactions
of 1,5- and 1,6-Dienes: Evidence in Support of
Carbocation Intermediates**
À
chemistry of the M C bond.
Our first approach to trapping the putative cation utilized
the Pd analogue of the Vitagliano complex 1 and dienylphe-
nol 3. Unlike direct Brønsted acid[4] and HgII [15] activation/
polycyclization, PdII prefers to coordinate and activate the
least substituted alkene,[16] ensuring activation at the termi-
nus. As shown in Scheme 1, the isolable C6F5CN adduct[17]
Jeong Hwan Koh and Michel R. GagnØ*
Biomimetic polyolefin cascade reactions[1,2] represent some of
the most challenging problems in reaction design, and their
products are ubiquitous in the natural world.[3] Since the
Brønsted–Lewis acids (BLAs) of Yamamoto et al. are the
only known synthetic catalysts for asymmetric catalytic
initiation of cation–olefin cyclizations,[4,5] we became inter-
À
ested in an alternative C C bond-forming cascade wherein
activation of a terminal alkene occurs with an electrophilic
PdII source. Although this process is uncommon, it is
precedented in the catalysis of the Cope rearrangement
with [PdCl2(RCN)2] [Eq. (1)] by Overman et al.[6] Fragmen-
Scheme 1. Phenol trapping of an intermediate cation and reductive
cleavage of the stable Pd alkyl complex.
tation of a cationic intermediate in the opposite regiodir-
ection was proposed to generate a new diene and a PdII
complex. More recently, Widenhoefer et al.[7] and Toyota,
Ihara et al.[8] demonstrated that nucleophilic enols lead to
carbocyclic products by b-hydride elimination[9] or protona-
tion.[10]
efficiently (1 h, RT, CH2Cl2) converted 3 to a new metal-
containing product devoid of alkene resonances (1H NMR
spectroscopy) as a 93:7 mixture of isomers according to
31P NMR spectroscopy. This compound is stable up to 1008C,
though demetalation with NaBH4 at room temperature
rapidly[14b] yielded tricycle 4 in 90% yield (two steps) and
d.r. > 99:1.[18]
Since a single diastereomer was observable in the crude
demetalation product, we surmised that the isomer mixture
for the Pd alkyl complex must result from epimers at the
metal-containing stereocenter, a situation suggestive of com-
peting chair–chair and boat–chair transition states,[19] each
with a degree of concertedness in the C C/C O bond-
forming event, that is, a free carbocation is not likely formed
[cf. Eq. (1)].[1,20] Pincer complex [Pt(PPP)](BF4)2 (2, PPP =
bis(2-diphenylphosphanylethyl)phenylphosphane),[21]
derived from commercially available triphos, provided the
intermediate alkyl complex with a slightly higher diastereo-
selectivity (96:4), and 4 in similarly high yield (87%) and
selectivity (> 99:1).
Although substituent effects[11] and stereochemical stud-
ies[6c] support a cationic and cyclic intermediate, respectively,
the exact nature of this intermediate is unclear, and direct
evidence for this cation is lacking.[12] We therefore initiated a
plan that first gathered evidence supporting the intermediacy
of the carbocyclic cation, while also determining whether it
could function as a point for initiating new metal-mediated
reactivity. The key to our pursuit was a recent report by
Vitagliano et al. of a dicationic Pt complex of a pyridyl bis-
phosphane pincer ligand [Pt(PNP)](BF4)2 (PNP = 2,6-bis(di-
phenylphosphanylmethyl)pyridine) that catalyzes the dime-
rization of ethylene and 2-methyl-2-butene.[13,14] Intermolec-
ular nucleophilic addition of 2-methyl-2-butene to coordi-
À
À
[*] J. H. Koh, Prof. M. R. GagnØ
Department of Chemistry
University of North Carolina at Chapel Hill
Chapel Hill, NC 27599-3290 (USA)
Fax: (+1)919-962-6342
E-mail: mgagne@unc.edu
[**] This work was supported by the NIH (GM-60578); we also thank Dr.
Cheryl Mascarenhas and Ms. Claire Catteral for related experiments.
M.R.G. is a Camille Dreyfus Teacher Scholar.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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DOI: 10.1002/anie.200453913
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Communications
To explore the possibility of cascading the putative cation
in a polycyclization reaction,[1] we examined the reaction of
trienylphenol 5 with 2 (Scheme 2). As before, cyclization was
rapid (4 h), and 31P NMR analysis of the resulting Pt alkyl
carbocation intermediate. The reaction of 10 with 2 yielded a
new ketone-containing organometallic product that was free
of alkene resonances. Reductive removal of the carbocycle
(NaBH4) provided cis-fused bicyclic
alcohol 11 (Scheme 2, 90%, d.r.
> 95:5). This reaction is most succinctly
explained by cyclogeneration of a car-
bocation, ring-expanding/contracting
pinacol rearrangement (A),[25] and Pt
À
=
C and C O reduction. Mechanistic
analysis followed from Prins-initiated
formation of cations[26] which similarly
rearrange to provide cis-fused bicyclic
ketones. Complex 1 also provided 11 in high yield (93%) and
diastereoselectivity (d.r. > 95:5).
The pincer-ligated complexes 1 and 2 uniquely provide a
solution to the notion of trapping/cascading the putative
intermediate obtained from electrophilic carbocyclization of
1,5- and 1,6-dienes. The variety of trapping reactions (heter-
oatom addition, cation–olefin, and pinacol rearrangement)
are individually consistent with a cationic intermediate, but
taken together provide a compelling case for Overmanꢀs
proposal that cyclization-induced rearrangements proceed
through carbenium ion intermediates. Furthermore, the data
indicate that 1,5-dienes do not represent a boundary con-
dition for electrophilic carbocyclization/cation generation;
other diene arrangements can participate.
Scheme 2. Interception of cations generated with 2. Compound 8 was
characterized by X-ray crystallography. a: 1) 2, 1.05 equiv Ph2NMe,
CH2Cl2, RT, 1–4 h; 2) NaBH4, MeOH.
complex indicated that the product was formed with d.r.
ꢀ 95%. Treatment with NaBH4 provided tetracyclic 6 as a
96:3:1 mixture of diastereomers (GC), which was isolated as a
98:2 mixture of diastereomers after chromatography (86%
yield). Catalyst 1 provided the Pd alkyl complex as a 77:11:8:4
mixture of diastereomers, which simplified to 80:5:minors
after treatment with NaBH4; the major diastereomer purified
to 98:2 (77% yield).
Compound 7, wherein the activated alkene is positioned
6-exo to the forming six-membered ring, reacted with 2 to
provide a stable Pt alkyl complex as an 86:14 mixture of
isomers; reductive cleavage yielded 8 and 9 in the same ratio
(Scheme 2, 83% yield). Crystals of the major stereoisomer
grew from the oil, and X-ray crystallography confirmed the
relative configuration shown in Scheme 2.[22] The major
isomer apparently results from a chairlike transition state
that places the activated alkene in a pseudo-equatorial
orientation. The minor isomer 9 also contained a trans ring
junction, but a Me···Me NOE suggested a 1,3-diaxial dispo-
sition arising from a pseudo-axial position in the putative
transition state. The stereo-electronic reasons for this out-
come may be related to the pseudo-axial preference of
oxonium initiators in polyolefin cascades.[1,23,24] Complex 1
provided 8 with a 78:22 preference (85% yield).
Received: February 3, 2004 [Z53913]
Keywords: carbocations · carbocycles · cyclization · palladium ·
.
platinum
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