Gold(I)-catalyzed [2 + 2]-cycloaddition of allenenes

Article abstract of DOI:10.1021/ja075412n

A cationic phosphinegold(I)-catalyzed intramolecular [2 + 2]-cycloaddition between an allene and an alkene to form alkylidene?cyclobutanes is described. Additionally, the reported cycloisomerization reaction provides access to enantioenriched bicyclo-[3.2.0] structures using chiral biarylphosphinegold(I) complexes as catalysts. Copyright

Full text of DOI:10.1021/ja075412n

Published on Web 09/21/2007
Gold(I)-Catalyzed [2 + 2]-Cycloaddition of Allenenes
Michael R. Luzung, Pablo Mauleo´n, and F. Dean Toste*
Department of Chemistry, UniVersity of California, Berkeley, California 94720
Received July 20, 2007; E-mail: fdtoste@berkeley.edu
Table 1. Au(I)-Catalyzed [2 + 2]-Cycloaddition of Allenenesa
Stabilization of cationic intermediates as gold(I)-carbenoids is
proposed to be essential in a variety of gold(I)-catalyzed cycloi-
somerization reactions.1,2 In an effort to gain further insight into
the impact of this stabilization, we were inspired by parallels in
the reactivity of gold-complexed allenes and allyl cations3 to
consider the stepwise reactions of these species with nucleophilic
olefins (eq 1). Accordingly, we envisioned that addition of the
alkene to a gold(I)-activated allene would generate intermediate 1.
In analogy to the formal cycloadditions of alkenes and allyl cations,4
we hypothesized that the stability of the subsequent cationic species
would determine which cycloadduct formed. For example, cy-
clobutane 3 would be produced by intramolecular trapping of
cationic intermediate 1 to generate cation 2 or from its direct
reaction with the carbon-gold bond.5,6 Alternatively, a [3 +
2]-cycloaddition would arise via carbocation 4 which could be
stabilized as carbene resonance structure 5.7
To this end, reaction of 1,6-allenene 6 with 5 mol % of Ph3-
PAuCl and AgBF4 in 0.1 M CH2Cl2 cleanly afforded 82% yield of
[2 + 2]-cycloadduct 78 (Table 1, entry 1). Under these conditions,
a variety of aryl-substituted alkenes underwent the gold(I)-catalyzed
intramolecular [2 + 2]-cycloaddition with allenes (Table 1).9 For
example bicyclo-[3.2.0] carbocycle 15 was formed in 80% yield
from allenene 14 that does not possess a gem-dialkyl group in the
tether (entry 5). Other C-C double bonds within the substrate do
not compete with or inhibit the desired reaction (entry 2). Additional
substitution at the distal position of the allene does not impact the
course of the cycloaddition (entries 6 and 7). Notably, trisubstituted
olefin 20 underwent gold(I)-catalyzed [2 + 2]-cycloaddition,
furnishing cyclobutane 21 possessing an all-carbon quaternary
center (entry 8). The diastereoselectivity relative to substituents on
the tether was also examined. While substrate 22 having an allylic
methyl afforded 23 in 85% yield and 6:1 dr (entry 9), allenene 24
having a methyl substituent at the allenic position afforded 25 as a
single diastereomer (entry 10). Importantly, alkylidene cyclobutane
278 was produced as a single olefin isomer from the gold-catalyzed
cycloaddition of disubstituted allenene 26 (entry 11).
a Reaction conditions: 0.1 M allenene in CH2Cl2, 5 mol % of Ph3PAuCl,
5 mol % of AgBF4, rt. b Isolated yield after chromatography. c 0.1 M
CH3NO2, 10 h, rt.
obtained in the cycloaddition of allenenes containing a variety of
styrenyl aryl groups (entries 5-7).
The mechanistic hypothesis presented in eq 1 suggests that the
gold(I)-catalyzed cycloaddition proceeds through a stepwise mech-
anism involving a series of carbocationic intermediates. In accord
with a stepwise mechanism involving a benzylic cation, cyclobutane
30 was formed from the gold-catalyzed cycloaddition of trans- and
cis-alkenes 29 and 37 (eq 2). Moreover, gold(I)-catalyzed reaction
of 29 in the presence of methanol provided trans-cyclopentane 38
accompanied by a minor amount of cis-cyclobutane 30 (eq 3).12,13
We propose the sequence outlined in Scheme 1 as the likely
mechanism for the gold(I)-catalyzed reaction. Addition of the
With these results in hand, we examined the recently developed
chiral dinuclear gold(I)-biarylphosphine complexes10 as catalysts
for an enantioselective [2 + 2]-cycloaddition (Table 2). To this
end, reaction of allenene 29 with the catalyst generated in situ from
3 mol % of (R)-DTBM-SEGPHOS(AuCl)2 (28) and 6 mol % of
AgBF4 afforded cyclobutane 30 in 92% yield and 95% ee (Table
2, entry 1).11 The gold-catalyzed reaction provided cycloadduct 17
with excellent enantioselectivity from allene 16 that is substituted
at the distal carbon. Additionally, excellent enantioselectivity was
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10.1021/ja075412n CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Enantioselective Au(I)-Catalyzed [2 + 2]-Cycloadditiona
References
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N. D.; Sherry, B. D.; Toste, F. D. J. Am. Chem. Soc. 2007, 129, 5838.
(3) (a) Shi, X.; Gorin, D. J.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 5802.
(b) Wang, S.; Zhang, L. J. Am. Chem. Soc. 2006, 128, 1442. (c) Funami,
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a Reaction conditions: 28 (3 mol %), AgBF4 (6 mol %), DCM (0.1 M),
4 °C. b Isolated yield after chromatography. c Reaction run at rt.
(4) For reviews, see: (a) Hoffman, H. M. R. Angew. Chem., Int. Ed. 1984,
23, 1. (b) Harmata, M. Tetrahedron 1997, 53, 6235.
(5) (a) Nakamura, I.; Sato, T.; Yamamoto, Y. Angew. Chem., Int. Ed. 2006,
45, 4473. (b) Dube´, P.; Toste, F. D. J. Am. Chem. Soc. 2006, 128, 12062.
(c) Wang, S.; Zhang, L. J. Am. Chem. Soc. 2006, 128, 1427. (d) Lian,
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Scheme 1. Proposed Mechanism of [2 + 2]-Cycloaddition
(6) A related mechanism has been proposed in the gold-catalyzed [2 +
2]-cycloaddition of propargyl esters and indole; see: Zhang, L. J. Am.
Chem. Soc. 2005, 127, 16804.
(7) Huang, X.; Zhang, L. J. Am. Chem. Soc. 2007, 129, 6398.
(8) Structure assigned by X-ray crystallography (see Supporting Information).
(9) Under identical reaction conditions, the analogous methyl-substituted
alkene returned mainly starting material accompanied by small amounts
of cycloisomerized product (see ref 17c)
(10) (a) Hamilton, G. L.; Kang, E. J.; Mba, M.; Toste, F. D. Science 2007,
317, 496. (b) Tarselli, M. A.; Chianese, A. R.; Lee, S. J.; Gagne´, M. R.
Angew. Chem., Int. Ed. 2007, 46, 6670. (c) Liu, C.; Widenhoefer, R. A.
Org. Lett. 2007, 9, 1925. (d) LaLonde, R. L.; Sherry, B. D.; Kang, E. J.;
Toste, F. D. J. Am. Chem. Soc. 2007, 129, 2452. (e) Zhang, Z.;
Widenhoefer, R. A. Angew. Chem., Int. Ed. 2007, 46, 283. (f) Johansson,
M. J.; Gorin, D. J.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc. 2005,
127, 18002. (g) Mun˜oz, M. P.; Adrio, J.; Carretero, J. C.; Echavarren, A.
M. Organometallics 2005, 24, 1293.
(11) Under identical conditions, xylyl-BINAP(AuCl)2 (85% ee) and SEGPHOS-
(AuCl)2 (88% ee) provided 30 with slightly lower selectivity.
(12) For gold-catalyzed alkoxycyclizations of enynes, see: (a) Nieto-Oberhuber,
C.; Mun˜oz, M. P.; Lo´pez, S.; Jime´nez-Nu´n˜ez, E.; Nevado, C.; Herrero-
Go´mez, E.; Raducan, M.; Echavarren, A. M. Chem.sEur. J. 2006, 12,
1677. (b) Buzas, A. K.; Istrate, F. M.; Gagosz, F. Angew. Chem., Int. Ed.
2007, 46, 1141. (c) Genin, E.; Leseurre, L.; Toullec, P. Y.; Geneˆt, J.-P.;
Michelet, V. Synlett 2007, 11, 1780.
(13) Under these conditions (CH3NO2, MeOH (3 equiv), 4°C), reaction of 29
catalyzed by 28 afforded 38 (75%) and 30 (12%), both as racemic
mixtures. See Supporting Information for additional examples of the gold-
catalyzed carboalkoxylation of allenenes.
(14) The observation that 27 was formed as a single olefin isomer suggests
that this addition occurs preferentially anti to the phosphinegold(I) complex
and trans to the larger allene substituent (RL in Scheme 1).
nucleophilic alkene to gold(I)-activated allene 39 results in the
formation of a carbocationic intermediate.14 In the presence of
methanol, kinetically formed carbocation 40 is trapped to give trans-
cyclopentane 41. That the cyclopentane stereochemistry of the
methanol adduct is opposite to that of the cyclobutane product
implies that the initial cyclization is reversible.15,16 Therefore, in
the absence of an exogenous nucleophile, the reaction proceeds
through cis-disubstituted intermediate 42. Cyclobutane 43 is then
formed from reaction of the vinyl-gold with the benzylic carboca-
tion.
In conclusion, we have developed the first transition-metal-
catalyzed cycloisomerization of allenenes to alkylidene-cyclobu-
tanes.17,18 The [2 + 2]-cycloaddition reaction provides access to
enantioenriched bicyclo-[3.2.0] structures using chiral biarylphos-
phinegold(I) complexes as catalysts.19 In accord with the mecha-
nisms of previously reported gold(I)-catalyzed cycloisomerizations,
the reaction is proposed to proceed through a series of cationic
intermediates. In gold-catalyzed enyne cycloisomerization reactions,
the interaction of the â-carbon of the vinyl-gold species with a
carbocation results in the formation of gold(I)-stabilized cyclopro-
pylcarbinyl cation.2,12 In contrast, the results reported herein suggest
that, when this type of resonance-stabilized cation is not available,
vinyl-gold species preferentially react with electrophiles to sub-
stitute the carbon-gold bond.5,20 Further studies on this mechanistic
dichotomy are ongoing and will be reported in due course.
(15) The absence of deuterium loss in the gold(I)-catalyzed formation of d-38
from d-29 suggests that the methyl ether is not formed from addition of
methanol to the styrene moiety of a 1,4-diene.17
(16) Under the reaction conditions for its formation, methyl ether 38 is not
formed from cyclobutane 30.
(17) For transition-metal-catalyzed cycloisomerization of allenenes, see: (a)
Trost, B. M.; Tour, J. M. J. Am. Chem. Soc. 1988, 110, 5231. (b) Kang,
S.-K.; Ko, B.-S.; Lee, D. M. Tetrahedron Lett. 2002, 43, 6693. (c) Makino,
T.; Itoh, K. J. Org. Chem. 2004, 69, 395. (d) Na¨rhi, K.; Franze´n, J.;
Ba¨ckvall, J. E. Chem.sEur. J. 2005, 6937. (e) Mukai, C.; Itoh, R.
Tetrahedron Lett. 2006, 47, 3971. See also ref 10b.
Acknowledgment. We gratefully acknowledge NIHGMS (R01
GM073932), Merck Research Laboratories, Bristol-Myers Squibb,
Amgen Inc., Boehringer Ingelheim, and Novartis for funding. P.M.
thanks the Spanish MEC for a postdoctoral fellowship. We thank
Takasago for their generous donation of chiral ligands, and David
Wang for preliminary experiments.
(18) Recent examples of thermal [2 + 2]-cycloaddition of allenes: (a) (a) Ohno,
H.; Mizutani, T.; Kadoh, Y.; Miyamura, K.; Tanaka, T. Angew. Chem.,
Int. Ed. 2005, 44, 5113. (b) Ohno, H.; Mizutani, T.; Kadoh, Y.; Aso, A.;
Miyamura, K.; Fujii, N.; Tanaka, T. J. Org. Chem. 2007, 72, 4378.
(19) For enantioselective [2 + 2]-cycloadditions of allenes with electron-
deficient alkenes, see: Narasaka, K.; Hayashi, Y.; Shimadzu, H.; Niihata,
S. J. Am. Chem. Soc. 1992, 114, 8869.
(20) Cycloisomerization of 1,5-enynes is stereospecific with regards to olefin
geometry (see ref 2c) and the [2 + 2]-cycloaddition in eq 2 is not.
Supporting Information Available: Experimental procedures and
compound characterization data (PDF). This material is available free
of charge via the Internet at http://pubs.acs.org.
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