There are two possible pathways for the intermolecular
coupling reaction of monodiazoacetates N2CHCO2R (15)
catalyzed by complex 1: the first is bimolecular reaction
of the ruthenium carbene intermediate [Ru(2,6-Cl2TPP)-
(CHCO2R)] (16) (route 1 in Scheme 1), and the second is
1:1 mixture of the trans (22) and cis isomer (23) in an overall
yield of 30%, while with catalyst [Cu(MeCN)4]PF6, a 1:2
mixture of 22:23 was formed in 11% isolated yield.1q
Under similar conditions, we treated 21 with 1 mol %
[Ru(2,6-Cl2TPP)(CO)] (1). After the reaction was completed,
the resulting solution was concentrated and the products were
identified by 1H NMR spectroscopy. Importantly, only a trace
amount of the trans isomer was detected (22:23 < 1:40).
Patulolide B (23) was isolated in 67% yield (Scheme 2).
Scheme 1
Scheme 2
reaction of the ruthenium carbene intermediate 16 with the
diazo compound (route 2 in Scheme 1). Analogous pathways
can be proposed for the intramolecular coupling reaction of
bisdiazoacetates catalyzed by 1.
In conclusion, the ruthenium porphyrin 1 is an excellent
catalyst for coupling reactions of diazo compounds with
remarkable cis selectivity. The mechanism was proposed to
involve the reaction of a ruthenium carbene intermediate with
a diazo compound. The present protocol provides a con-
venient entry to cis-alkenes, including macrocyclic com-
pounds featuring a cis-alkene motif such as Patulolide B,
which are of interest in organic synthesis.
To provide mechanistic insight, we reacted ruthenium
porphyrin 1 with slightly excess methyl diazoacetate under
an argon atmosphere at -78 °C. When the resulting solution
was followed by 1H NMR spectroscopy, five peaks that did
not originate from the reactants were observed. The peaks
at δ ) 6.24 and 3.77 ppm can be attributed to the coupling
product, and the three peaks at δ ) 13.28 (1H), 8.38 (8H),
and 2.24 ppm (3H) are assignable to the intermediate 16 (R
) Me). When the solution was left standing at room
temperature for 10 h, the ruthenium carbene species 16 was
still detected, although some decomposition had occurred.
Further addition of methyl diazoacetate to the solution at
this stage increased the amount of the coupling product.
Therefore, we propose that the coupling reaction of diazo-
acetates catalyzed by 1 preferentially proceeded by route 2.
The selective formation of cis-alkenes from this pathway
resembles the observations in RuCl2(PPh3)3-catalyzed inter-
molecular coupling of ethyldiazoacetate.1s
Acknowledgment. This work was supported by the Hong
Kong Research Grants Council (HKU 7099/01P), the Uni-
versity Development Fund of HKU, and the Area of
Excellence Scheme (AoE/P-10/01) established under the
University Grants Council of HKSAR. G.Y.L. thanks the
Shanghai Institute of Organic Chemistry and the Croucher
Foundation of Hong Kong for the postgraduate studentship.
Supporting Information Available: Detailed experi-
mental procedures, spectral data of compounds, and CIF file
for the crystal structure of 5e, along with reaction schemes
showing the structural formulas of all the organic compounds
involved in this work. This material is available free of
Patulolides A (22) and B (23) are biologically active
macrocyclic lactones isolated from Penicillium urticae
mutant S11R59.6,7 These lactones can be synthesized through
ring-closing esterification8 or alkene metathesis.9
Doyle and co-workers first employed metal-catalyzed
intramolecular coupling of 21 to synthesize 22 and 23.1q
Using [Rh2(CH3CO2)4] as a catalyst, the reaction afforded a
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