Divergent insertion reactions of Pt-carbenes generated from [3+2] cyclization of platinum-bound pyrylliums

Article abstract of DOI:10.1002/chem.200801887

The divergent insertion reactions of Pt-Carbenes generated from [3+2] cyclization of platinum-bound pyrylliums was studied. The enynals 7 bearing an olefinic pendant were successfully cyclized through Huisgen-type cycloaddition to the tetracyclic Pt-carbe

Full text of DOI:10.1002/chem.200801887

COMMUNICATION
DOI: 10.1002/chem.200801887
Divergent Insertion Reactions of Pt–Carbenes Generated from [3+2]
Cyclization of Platinum-Bound Pyrylliums
Chang Ho Oh,*[a] Ji Ho Lee,[a] Sung Min Lee,[a] Hyun Jik Yi,[a] and Chang Seop Hong[b]
Among the various synthetic strategies, which lead to
polycycles containing a central seven-membered carbocycle,
[4+3], or [5+2] cycloadditions are particularly attractive be-
cause of their inherent potential to achieve rapid increase in
skeleton diversity.[1] During the course of our scientific en-
deavors to obtain a general and modular entry to seven-
membered ring-containing natural products,[2] we recently
reported a highly unique behavior of Pt–carbene complexes
(such cis- and trans-B).[3] The cis-B and trans-B are two
plausible intermediates formed via a Huisgen-type [3+2] cy-
cloaddition of A [see Eq. (1)],[4] where the cis- and trans-re-
lationship was assigned between the bridged oxygen and the
group Z.
we have reported a Au-catalyzed reaction of enynals (such
as 1) to yield 2,3,10,10a-tetrahydrobenzo[f]azulen-9(1H)-one
(like 2) via [3+2] cycloaddition [Eq. (2)].[5] Pt-catalyzed cyc-
lization of 1, however, afforded 3 as the major product, pre-
sumably formed via oxygenation of intermediate B.[6] Note
that elimination of H1 from intermediate B would form 2.
Elimination of H2 from B could result in sequential migra-
tion eventually to form the naphthalene derivative.[7] Con-
trarily, H3, if attached to an sp3 carbon as in 4, would be
eliminated to give diene product 5 [Eq. (3)].[8]
The preliminary results using molecular modeling show
that trans-B is less likely to be formed due to the steric hin-
drance between the incoming double bond and the Z group;
in addition trans-B has a anticoplanar relationship between
the bridged oxygen and the group Z. In the cases involving
a five-membered ring formation in the third cycle (n=5),
[a] Prof. C. H. Oh, J. H. Lee, S. M. Lee, H. J. Yi
Department of Chemistry, Hanyang University
Sungdong-Gu, Seoul 133-791 (Korea)
Fax : (+82)22299-0762
During our extension of this methodology to the synthesis
of the natural product dichotenone,[9] we needed a function-
alized six-membered ring in the third cycle (n=6). We pre-
viously reported the reaction of 6, possessing a benzyloxy
group at the propargylic position [Eq. (4)], where we found
that the Pt–carbene intermediate (cis-B) could undergo CH
insertion into C–H4 of the d-position to 6a.[10]
Homepage: http://hychemistry.hanyang.ac.kr/gos
E-mail: changho@hanyang.ac.kr
[b] Prof. C. S. Hong
Department of Chemistry, Korea University
Sungbook-Gu, Seoul 136-704 (Korea)
Then, we focussed on substrates 7 which do not contain a
benzyloxy group to elaborate other possible insertions
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200801887.
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71

isolated in excellent yields. During the reaction 8g and 8h
were spontaneously isomerized to spirocycles 9g and 9h in
65 and 82% yields, respectively. Products 8a–f also were
smoothly isomerized to the corresponding spiro compounds
9a–f with the retention of stereochemistry. It is worthwhile
Table 1. Metal-catalyzed reactions of enynal 7a.
under Pt catalysis.[11] Here we
wish to report the highly
unique CH insertion into C–H5
of the proposed intermediate B
to form the corresponding
fused cyclopropanes.[12] Thus,
we examined the reaction of 7a
under various conditions in
order to construct a core sub-
structure such as 2a, which is
found in many natural products
such as faveline,[13] barbatu-
sol,[14] pisiferin,[15] rosmaridiphe-
nol,[16] xochitlolone.[17] PtCl2-
catalyzed reaction of 7a was
summarized in Table 1. First of
all, the reaction of 7a with
Catalysts (5 mol%)
Solvent
T [8C], t [h]
Products (Yield/%)
1
2
3
4
5
6
7
8
9
PtCl2
PtCl2
ACHUTNERGN[NUG PtCl2HCATUNGTRENN(UGN dppe)]
PtCl2
PtCl2
PtCl2
PtCl2
PtCl2
PtCl2
toluene
toluene
toluene
toluene
120, 2
120, 4
120, 2
80, 1
8a (54), 9a (24)
8a (~0), 9a (38)
8a (83)
8a (95)
80, 12
80, 1
8a (90), 9a (5)
8a (95)
CH3CN, EDC
p-dioxane
toluene/air
toluene/water
80, 12
80, 1
8a (90), 9a (5)
8a (95)
80, 1
8a (5)
PtCl2 as the catalyst proceeded well under reflux in toluene
to furnish a mixture of unexpected products 8a and 9a in 54
and 24% yields, respectively, without forming product 2a
to note that all products 8 and 9 were isolated with high
levels of stereoselectivity, although our reactions were ex-
pected to afford the complex reaction mixtures due to
newly-forming multiple stereogenic centers.
(entry 1). This was a very unusual reaction in which the in-
b
À
sertion of a Pt–carbene species into C H bond formed the
corresponding cyclopropanes such as 8.[18] Note that metal–
carbenes generally undergo cyclopropanation in the reaction
with alkenes. Several conditions were tested to optimize the
reaction efficacy. The longer reaction time under the same
conditions resulted in overreactions to yield 9a as a major
product (entry 2). Surprisingly, when 7a was treated with
[PtCl2ACHTUNGTRENNUNG(dppe)] at 1208C for 2 h in toluene, the reaction af-
forded 8a exclusively in 83% yield (entry 3). Simply lower-
ing the reaction temperature (808C) and the reaction time
(one hour) provided the best conditions leading to 8a in
95% yield (entry 4). This reaction was also successful in
other solvents, such as CH3CN, 1,2-dichloroethane (EDC),
and p-dioxane (entries 5–7). This reaction was not affected
by oxygen from air but severely affected by water (en-
tries 8–9). On the basis of the reaction trends, we proposed
that the spirocycle 9a might be formed via the initial cyclo-
propane 8a, since 9a became a major after prolonged reac-
tion times. To clarify this assumption, we examined the reac-
tion of 8a with 0.1 equvalent of p-toluenesulfonic acid in
benzene under reflux, where 9a was isolated in 91% yield.
TLC monitoring of the Pt-catalyzed reaction of 7a also re-
vealed that 8a was initially formed as a sole product and
then 9a was formed upon prolonged heating.
Using the present conditions (PtCl2 in toluene at 808C for
1–12 h), several substrates (7b–h) were examined to explore
the scope and limitations of this reaction (Scheme 1). Over-
all all substrates seemed to afford the corresponding prod-
ucts 8 in good to excellent yields. The products 8a–f were
Scheme 1. Pt-catalyzed cyclization under PtCl2 in toluene at 808C for 1–
4 h.
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Chem. Eur. J. 2009, 15, 71 – 74

Divergent Insertion Reactions of Pt–Carbenes
COMMUNICATION
for flash column chromatography (silica gel, n-hexane/EtOAc 20:1) to
afford the pure products 8a (95.2 mg, 95%) as a colorless oil. 1H NMR
(400 MHz, CDCl3): d=7.25–7.23 (m, 2H), 7.14–7.08 (m, 2H), 4.97 (d,
3J=6.0 Hz, 1H), 2.28–2.22 (m, 1H), 2.07–2.01 (m, 2H), 1.98 (s, 1H),
1.65–1.56 (m, 1H), 1.50–1.43 (m, 1H), 1.32–1.22 (m, 3H), 1.13 (s, 3H),
0.99 ppm (s, 3H); 13C NMR (100 MHz, CDCl3): d=135.24, 133.41,
127.46, 126.30, 124.21, 121.81, 74.98, 63.64, 36.12, 31.24, 29.46, 29.15,
28.50, 27.14, 26.99, 24.20, 18.15 ppm; IR (NaCl): n˜ =3026, 2950, 2865,
1608, 1487, 1462, 1024, 952 cmÀ1; HRMS: m/z: calcd for C17H20NaO:
263.1412; found: 263.1469. The spiro compounds 9a–h were formed upon
prolonged heating of the Pt reaction mixture or by TsOH-catalyzed iso-
merisation. Thus, a benzene solution (2.0 mL) of 8a (24.0 mg, 0.10 mmol)
in the presence of about 10% TsOH was heated for 2 h. The reaction so-
lution was cooled down to room temperature and partially concentrated
under vacuum and the residue was subjected for flash column chromatog-
raphy (silica gel, n-hexane/EtOAc 20:1) to afford the pure products 9a
(21.1 mg, 88%) as a colorless oil. 1H NMR (400 MHz, CDCl3): d=7.17–
In order to confirm the structure of 8, we needed at least
one good single crystal of 8. Fortunately, X-ray structure of
8b could be obtained (see Figure 1, so that we were able to
Figure 1. X-ray structure of 8b.
3
3
7.07 (m, 3H), 6.97 (d, J=7.2 Hz, 1H), 6.53 (d, J=10.0 Hz, 1H), 6.07 (d,
3J=9.6 Hz, 1H), 3.07 (ABq, Dd=76.0 Hz, 2J=16 Hz, 2H), 2.70–2.63 (m,
1H), 2.20–2.14 (m, 1H), 2.06–1.99 (m, 1H), 1.94–1.82 (m, 2H), 1.51 (dt,
3J=13.6, 4.0 Hz, 1H), 0.98 (s, 3H), 0.90 ppm (s, 3H); 13C NMR
(100 MHz, CDCl3): d=211.02, 135.42, 131.87, 129.97, 128.20, 127.97,
127.61, 126.41, 126.35, 57.51, 41.66, 37.40, 35.38, 30.31, 25.88, 23.64,
22.84 ppm; IR (NaCl): n˜ =3018, 2961, 2870, 1701, 1488, 1450, 1387, 1310,
1175, 1072 cmÀ1; HRMS: m/z: calcd for C17H20NaO: 263.1412; found,
263.1440.
confirm the relative structures of our products 8 by compari-
son of the spectral data. Mechanistically, intermediates A
would undergo [3+2] cycloaddition with a pendant double
bond to form the Pt–carbene complex B (Scheme 2). Pt–car-
bene B would undergo insertion to form 3 if there is a ben-
zylic–H of the d position; if no such CH bond is present, the
reaction would proceed with insertion into the tertiary CH
bond to form the cyclopropane ring like 8. Further heating
of the reaction mixture or a TsOH-catalyzed reaction of iso-
lated 8 cleanly resulted in an isomerization to form 9.
Acknowledgements
We would like to thank the Korea Science and Engineering Foundation
(R01-2007-000-20315-0) for financial support.
Keywords: asymmetric catalysis · carbenes · cyclization ·
insertion · platinum
ˇ
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Received: September 14, 2008
Published online: November 26, 2008
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