COMMUNICATION
Unusual regiodivergence in metal-catalysed intramolecular
cyclisation of c-allenolsw
Jannine L. Arbour, Henry S. Rzepa,* Andrew J. P. White and King Kuok (Mimi) Hii*
Received (in Cambridge, UK) 6th July 2009, Accepted 10th September 2009
First published as an Advance Article on the web 13th October 2009
DOI: 10.1039/b913295c
Different O-heterocycles can be obtained from a common
c-allenol precursor by using Ag, Zn or Sn catalysts; the results
were rationalised by molecular modelling.
Sn-mediated reaction was attenuated by replacing the diphenyls
in 1a with a cyclohexyl group 1c, such that 5-membered ring
formation became competitive (entry 7). The reaction catalysed
by Zn(OTf)2 was also sluggish at room temperature, although
the larger ring was still preferred (entry 8). At a higher
temperature, selectivity for the 6-membered ring product
remained unchanged for the system catalysed by Sn(OTf)2
(entries 2 vs. 3), while there was a switch in favour of the
smaller ring by Zn(OTf)2 (entries 4 vs. 5 and 8 vs. 9).
Intramolecular hydroalkoxylation of g-allenols 1 can potentially
afford 5- or 6-membered O-heterocycles 2 or 3via different
mechanistic pathways (Scheme 1):1 the former (5-exo-trig)
cyclisation is more common, and can be obtained using Pt2a
or Au2b catalysts, including enantioselective reactions,3 through
p-activation of the CQC bond. Conversely, the only known
catalytic example4 of a 6-endo/exo-dig cyclisation was achieved
at 130 1C using a lanthanide amide complex via CQC insertion
into Ln–O.5
Brønsted acid catalysis was investigated by addition of
30 mol% triflic acid to 1a. At room temperature, the formation
of 4 was observed in a lower yield (50%, r.t., 23 h) compared to
Sn(OTf)2.9 Likewise, acid-catalysed cyclisation of 1b led to 6a
and 6b (1 : 6 ratio). However, substrate 1cremained inert over
6 days (r.t.). These observations, accompanied by the switch of
selectivity for the 5-exo-trig compound at higher temperatures
for the Sn and Zn systems, suggest that a H+-catalysed
process is not likely to be significant.
In this communication, we report an unusual observation
in the intramolecular cyclisation of g-allenols, where the
regiochemistry of the process can be altered by using different
metal catalysts.6,7
The work initiated with the observation that g-allenol 1a
underwent 5-exo-trig cyclisation in the presence of a catalytic
amount of AgOTf to afford 2a.8 Subsequent screening of metal
triflates led to the serendipitous discovery of two catalysts that
effect complementary 6-exo-dig selectivity (Scheme 2). Under
virtually identical conditions, Sn(OTf)2 transformed 1a into
benzopyran 4via tandem C–O/C–C bond formations, while
Zn(OTf)2 favoured sequential C–O formations to furnish the
acetal structure 5 at a higher temperature (structures 4 and 5
were verified by X-ray crystallography, see the ESIw). Although
small amounts of 2a were detected in both reaction mixtures
(6 and 13%, respectively), 2a, 4 and 5 did not interconvert
when left exposed to the other catalysts, suggesting the operation
of competitive and irreversible processes.
DFT-based models were employed to provide a rationale
for the observed regiodivergence. Using g-allenol 1a as sub-
strate, with the counter-ion modelled as triflate (L = OTf,
X = SO) or trifluoroacetate (L = TFA, X = C), the 5-exo-trig
transition state (TS1, Scheme 4) resulting in 2a was tested on
group 11 metals (Cu, Ag and Au), for which there is reliable
experimental data. At the B3LYP/cc-pVDZ level of theory
(cc-pVDZ-pp for the metal), the activation free energies (DGz)
for TS1 (L = TFA) were calculated to be 26.7, 18.1 and
12.2 kcal molꢀ1, respectively, commensurate with experimental
observations that gold-catalysed reaction occurs at sub-ambient
conditions, silver at room temperature, and no reaction was
observed with copper under ambient conditions.
Calculated transition normal modes, illustrated as
animations in the web-enhanced Table 1 (M = Cu, Ag, Au)
and statically (Fig. 1), reveal that C–O bond formation is
assisted by concomitant deprotonation of the OH group
by the adjacent carbonyl of the ligand, the reaction completing
with a protonolysis of intermediate I (TS5). Modifying
L = OTf to L = TFA is predicted to reduce the barrier by
1.5 kcal molꢀ1, corresponding to a rate increase of ca. 12-fold
at ambient temperature. Indeed, this was verified experimentally:
1a underwent complete cyclisation in the presence of 15% of
The regiodivergence of these catalytic systems was similarly
observed with substrates 1b and 1c (Scheme 3, Table 1): while
AgOTf provided tetrahydrofurans 2b and 2c (entries 1 and 6),
corresponding reactions using Sn(II) and Zn(II) triflates
afforded tetrahydropyran rings as major products at ambient
temperature (entries 2, 4 and 8). In the case of 1b, a mixture of
double bond isomers 6a and 6b was obtained, acetal formation
was presumably prohibited for steric reasons. Rate of the
Department of Chemistry, Imperial College London, Exhibition Road,
South Kensington, London SW7 2AZ, UK.
E-mail: rzepa@imperial.ac.uk, mimi.hii@imperial.ac.uk
w Electronic supplementary information (ESI) available: Crystallo-
graphic data for compounds 4 and 5, experimental procedures, and
compound characterization (pdf). CCDC 726110 & 726111. For ESI
and crystallographic data in CIF or other electronic format see DOI:
10.1039/b913295c. Calculated coordinates and animated transition
state normal modes are provided via web-enhanced tables via the
HTML version of the article.
Scheme 1 5-exo-trig and 6-exo-dig cyclisation of g-allenols.
Chem. Commun., 2009, 7125–7127 | 7125
ꢁc
This journal is The Royal Society of Chemistry 2009
Arbour, Jannine L.
