Gold(I)-catalyzed ring expansion of cyclopropanols and cyclobutanols

Article abstract of DOI:10.1021/ja052831g

The rearrangement of 1-alkynyl cyclobutanols and cyclopropanols to alkylidene cycloalkanones catalyzed by cationic triarylphosphine gold(I) complexes is described. The reaction tolerates terminal alkynes as well as alkyl, aryl, and halo-substitution at the acetylenic position and stereoselectively provides a single olefin isomer. The gold(I)-catalyzed rearrangement is stereospecific with regard to substituents on the ring, thus providing a practical method for the stereoselective synthesis of highly substituted cyclopentanones from cyclopropanols. The reaction stereoselectively provides a single olefin isomer and is stereospecific with regard to substituents on the ring via sequential gold(I)-catalyzed ring expansion reactions. Copyright

Full text of DOI:10.1021/ja052831g

Published on Web 06/15/2005
Gold(I)-Catalyzed Ring Expansion of Cyclopropanols and Cyclobutanols
Jordan P. Markham, Steven T. Staben, and F. Dean Toste*
Department of Chemistry, UniVersity of California, Berkeley, California 94720
Received April 30, 2005; E-mail: fdtoste@berkeley.edu
Table 2. Scope of Au(I)-Catalyzed Ring Expansiona
Transition metal-promoted ring expansion reactions of 1-vinyl-
cycloalkanols provide a powerful method for construction of a
variety of cyclic ketones.1 Similarly, 2-alkylidenecycloalkanones
are potentially available from the corresponding rearrangement of
1-alkynylcycloalkanols; however, only a few examples of transition
metal-catalyzed expansion of 1-alkynylcyclobutanols to alkylidene-
cyclopentanones have been reported.2,3 A number of transformations
involving the addition of heteroatom4 nucleophiles or π-bonds5 to
gold(I)-activated alkynes have recently been described. We hy-
pothesized that related cationic gold(I) complexes might be capable
of catalyzing ring expansion6 reactions by promoting migration of
nucleophilic σ-bonds to alkynes.
On the basis of this hypothesis, treatment of alkynylcyclo-
propanol 1 with 1 mol % (PPh3)AuSbF6 produced desired alkylidene-
cyclobutanone 2 in 95% yield as a single olefin isomer (Table 1).7
The yield and rate of the rearrangement was improved by employing
electron-deficient arylphosphines as ligands. For example, when
the cationic gold complexes derived from tris(4-trifluoromethyl-
phenyl)phosphinegold(I) chloride (3) were utilized as the catalyst,
cyclobutanone 2 was produced in 99% yield after only 25 min.
Conversely, the reaction was significantly less efficient when
complexes bearing electron-rich ligands were employed as catalysts.
With these results in hand, we examined the scope of the tris-
(4-trifluoromethylphenyl)phosphine gold(I)-catalyzed ring expan-
sion (Table 2). A range of alkyl-substituted alkynes afforded good
to excellent yields of the expected cyclobutanone products (entries
1 and 2). Aryl substituents were uniformly well tolerated with
electron-withdrawing, electron-donating, and halide-substituted aryl
alkynyl cyclopropanols expanding with excellent yields (entries
3-6). Notably, iodoalkynyl cyclopropanol 20 smoothly underwent
expansion catalyzed by 1 mol % 3, providing vinyl iodide 21 in
88% yield (entry 10). Trimethylsilyl and tert-butyldimethylsilyl
ethers also undergo gold(I)-catalyzed ring expansion in excellent
yields in the presence of 2 equiv of methanol (entries 7-9). The
alkyne need not be substituted, as demonstrated by gold(I)-catalyzed
conversion of alkyne 18 into 2-methylenecyclobutanone 19 (entry
a Reaction conditions: 0.5-5.0% 3 in CH2Cl2, rt. b MeOH (2 equiv)
added. c Determined by 1H NMR vs internal standard (mesitylene). d 4:1
mixture of cyclobutanone/cyclopentenone.
9). Furthermore, cationic gold(I) complex 3 promotes the selective
Table 1. Ligand Effects on Au(I)-Catalyzed Ring Expansion
migration of the more substituted carbon of 2-substituted cyclo-
propanols 22 and 24 to afford substituted cyclobutanones 23 and
25 (entries 11 and 12).
Alkynylcyclobutanols were also found to be viable substrates
for gold(I)-catalyzed ring expansion.8 Reaction of cyclobutanol 26,
prepared in two steps from cyclobutanone 7, provided 2-methylene-
cyclopentanone 27 in 73% yield (entry 13). Furthermore, bicyclic
cyclopentanone 29 and spiro ring systems 31 and 33 were likewise
obtained with selective migration of the more substituted carbon
of the cyclobutanol.
We envisioned two possible mechanisms for this rearrangement
(eq 1). In mechanism a, coordination of cationic gold(I) to the
alkyne moiety induces a 1,2-alkyl shift. Mechanism b involves
gold(I) activation of the cycloalkanol6,9 to give alkyl gold(I) complex
that subsequently undergoes insertion into the alkyne.10 The (E)-
a Time to 99% conversion of 1 by 1H NMR. b Determined by 1H NMR
vs internal standard (mesitylene). c 5% cyclopentenone. d 13% cyclopen-
tenone.
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J. AM. CHEM. SOC. 2005, 127, 9708-9709
10.1021/ja052831g CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
gold(I)-catalyzed rearrangements of strained ring systems are
ongoing in our laboratories.
Acknowledgment. We gratefully acknowledge the University
of California, Berkeley, NIHGMS (R01 GM073932-01) Merck
Research Laboratories, Bristol-Myers Squibb, Amgen Inc., DuPont,
GlaxoSmithKline, and Eli Lilly & Co. for financial support.
olefin geometry of the resulting alkylidene cycloalkanes11 and the
selective migration of more substituted cycloalkanol carbons is most
consistent with mechanistic hypothesis a. Gold(I)-catalyzed re-
arrangement of substituted cyclopropanols 34a-d further supports
mechanism a and provides insight into the stereoelectronic demands
of ring expansion (eq 2). Consistent with the expected migratory
aptitude, gold(I)-catalyzed rearrangement of 34a afforded only 35a.
Increasing the size of the alkynyl substituent to phenyl in 34b
produced a decrease in the selectivity presumably as a result of an
increase in A1,3 strain between the R1 and R groups in proposed
transition state A. This interaction is more pronounced between R2
and R as demonstrated in the ring expansion of 34c, which
selectively furnished cyclobutanol 36c derived from migration of
the less substituted carbon.12 In accord with this hypothesis, reaction
of terminal alkyne 34d favors migration of the more substituted
carbon as a result of a decrease in A1,3 strain between R2 and R in
transition state A.
Supporting Information Available: Experimental procedures and
compound characterization data. This material is available free of charge
via the Internet at http://pubs.acs.org.
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on the ring. Thus, a sequence involving two gold(I)-catalyzed ring
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