Rearrangement of Alkynyl Sulfoxides Catalyzed by Gold(I) Complexes

Link: http://pubs.acs.org/cgi-bin/abstract.cgi/jacsat/asap/abs/ja070789e.html

From Prof. F. Dean Toste's group at University of California, Berkeley, CA

This article appeared recently in JACS ASAP from Prof. Toste's group at UC, Berkeley, demonstrating the utility of gold(I) complex as a catalyst for formation of gold-carbenoid species from alkynes and their subsequent reactions. The reaction was proposed to start with an activation of an alkyne with gold(I) catalyst, followed by an attack from a nucleophile (attached to a leaving group). Electron from gold species then moved in to form a carbenoid species concurrently with the expulsion of the leaving group.

In this paper, the nucleophile employed was sulfoxide which would generate sulfonium ion as a leaving group upon attacking gold-activated alkyne. It was found that under the reaction conditions, Friedel-Craft type reaction occurred to give ketone 3 as shown in Equation 2 above. Initially, several ligands were screened. The best result was found in an NHC ligand carrying mesitylene groups (IMes).

The reaction was screened with a variety of substrates. All reactions proceeded well, for instance, electron-rich as well as electro-poor aryl systems tolerated well. In addition, substitutions at both propargylic and homopropargylic positions proceeded without problem. Notably, in entry 5 one diastereomer (as shown) was more reactive than the other.

A marked difference was seen between entries 6, and 7 and entry 8. When substituent of alkyne is non-aliphatic (entries 6, 7), 5-exo-dig mode of cyclization was observed. But when the substituent was aliphatic group, as an ethyl group in 18, 6-endo-dig cyclization prevailed. These modes of mechanism are summarized in the scheme below.

With this mode of reaction with aliphatic substituent, complex furan 22 could be prepared in one step from diyne 20 in 56% yield.

Additional experiment with sulfimine 27 to generate N-tosyl enamine 28 confirmed that the oxygen atom was delivered intramolecularly from sulfur.

Gold(I) complexes were also found to catalyze the conversion of propargyl sulfoxides to alpha-thioenones in high yields as shown in equations below.

In this case, (dimethylsulfide)gold(I) chloride proved to be a better catalyst and the reaction afforded enones 31 from propargyl sulfoxides 29 with excellent tolerance for substitution on the alkyne and the sulfoxide. Additionally, secondary and tertiary propargyl sulfoxides react under these conditions to provide trisubstituted (eq 6) and tetrasubstituted alkenes. For example, sulfide 33 was obtained from sulfoxide 32 in preference to cycloisomerization of 1,5-enyne.

In analogy to the mechanism described in Scheme 1, this rearrangement is postulated to proceed through gold(I)-promoted sequential 5-endo-dig cyclization/cleavage of the S-O bond leading to gold(I)-carbenoid intermediate 30 which undergoes a 1,2-sulfide shift. In a separate cross-over experiment, the intramolecular 1,2-sulfide shift process was confirmed as there was no cross-over product observed as shown in the equation below. Note that the SMs should be 29b and 29c and the products should be 31b and 31c, respectively.

This paper has presented an important aspect of reactivity of gold catalyst with alkynes and provided a method for an efficient generation of gold-carbenoid species.