James R. Vyvyan, PhD
, Western Washington University
A significant portion of year 2 was
used to explore the Au-catalyzed formation of substituted lactones and
tetrahydropyrans. Last year we reported
the conversion of ester 1 to lactone
2 using a Au(III) catalyst (Figure
1). Substrate 3 with both ortho-positions
blocked to prevent a competing Claisen rearrangement and a carboxylic acid
replacing the ester, we found that lactone 2
was produced in quantitative yield using Ph3PAuOTf catalyst.
Similarly, blocking both ortho-positions of diol 4 resulted in an improved yield of
tetrahydropyran 5 (Figure 2). In
each case the tetrahydropyran product was exclusively of the cis-relative configuration.
Capitalizing on the high yield and
stereospecificity of this transformation, we completed a synthesis of (±)-centrolobine
using this cyclization reaction (Figure 3). Addition of 4-pentenylmagnesium
bromide to anisaldehyde resulted in secondary alcohol 6 in good yield. Grubb's
second-generation catalyst was used to promote an olefin cross metathesis
between 6 and cis-2-buten-1,4-diol to produce allylic alcohol 7.
Mitsunobu etherification of 7
with 2,4,6-trimethylphenol gave the allyl aryl ether 8 which cyclized to form tetrahydropyran 9 upon treatment with Ph3PAuOTf. A B-alkyl
Suzuki coupling of 9 with the THP ether
of 4-iodophenol produced 10 which
was deprotected to produce (±)-centrolobine (11).
During the course of many, but not
all, of our gold-catalyzed rearrangement reactions, we observed the formation
of a gold film on the surface of the reaction vessel (Figure 4). Further investigation revealed that the film
consists of aggregated gold nanoparticles.
The film has been characterized with AFM, XRD, and ICP-MS to date. When the initial reaction solution is removed
from the reaction vessel, the gold film rinsed with fresh solvent, and
additional substrate added, the rearrangement reaction proceeds quickly. This
indicates to us that the gold film is capable of catalyzing the rearrangement
reaction and a soluble gold(I) or gold(III) complex is not required for
catalysis. Current work is further
exploring the nature of the gold film and its catalytic properties.
4. Gold film on the surface of an NMR
tube and AFM image of the film.