Synthesis of 2-Cyclopentenones by Gold(I)-Catalyzed Rautenstrauch Rearrangement

Abstract

The importance of cyclopentenones as building blocks for organic synthesis continues to inspire the development of general methods for their stereoselective preparation. [1][2][3] In 1984, Rautenstrauch reported that palladium(II) complexes catalyzed the isomerization of 1-ethynyl-2-propenyl acetates (1) to cyclopentenones (eq 1). 4 This reaction and related rearrangements 5 are proposed to proceed through a metal carbene intermediate, such as 2, arising from a 1,2-acetate migration. While the Rautenstrauch rearrangement provided an efficient route to cyclopentenones, it was limited to the preparation of achiral cyclopentenones substituted at the 2 and 3 positions (eq 1). On the basis of recent examples of gold(I)-catalyzed cyclizations of enynes, 6 we hypothesized that these catalysts might afford an increase in the scope of this reaction and allow the preparation of chiral cyclopentenones.In light of our previous success employing Ph 3 PAuOTf in methylene chloride for carbon-carbon bond formation, 6b,7 we chose this catalyst system in preliminary studies of the rearrangement (eq 2). To develop catalysts that would permit the synthesis of chiral cyclopentenones, we initiated our investigation with a substrate (4) containing a trisubstituted olefin. We were pleased to find that rearrangement of 4, catalyzed by 5 mol % Ph 3 PAuOTf in methylene chloride, did afford desired cyclopentenone 5, however, in only 30% yield. Examination of the effect of solvent on the reaction revealed that acetonitrile produced the desired adduct with a marked improvement in yield. The yield was further improved by changing the ester from acetate to pivaloate. 8 With optimized reaction conditions in hand, we set out to define the scope of the cyclopentenone synthesis. The reaction is highly tolerant of substitution at the acetylenic position of the 1-ethynyl-2-propenyl pivaloates (Table 1). In addition to unsubstituted alkynes, the gold(I)-catalyzed reaction proceeded smoothly with substrates containing aryl-(entry 2), alkyl-(entry 3), and vinyl-substituted alkynes (entry 4). Cyclization of the latter produced exo-methylene cyclopentenone 13 after isomerization of the iso-propenyl group into conjugation with the ketone. The reaction also showed excellent scope with respect to substitution on the olefin. Specifically, 1,1-disubstituted (entries 1-4), 1,2-disubstituted (entry 5), and cyclic (entries 6 and 7) alkenes participated in the cyclization. Rearrangement of styrenyl substrates 14 and 18 afforded 3-phenylcyclopentenones 15 and 19 as a result of olefin isomerization into conjugation with the aryl group.A 1:1 diastereomeric mixture of 20, derived from (S)-(-)-perillaldehyde, underwent Au-catalyzed isomerization to produce bicyclic enone 21 as a 1:1 mixture of diastereomers (eq 3). We envisioned two scenarios to account for this diastereoselectivity: the stereochemistry of the starting ester is lost in generating a carbene-like intermediate (such as 2) that undergoes subsequent cyclization with no selectivity, or the stereochemist...

Gold Catalysis: Synthesis of 3‐Acylindenes from 2‐Alkynylaryl Epoxides

“…Then, the remaining C À O bond of the former epoxide ring is broken and an even more delocalized carbenium ion 19 can be formed. In Scheme 3 the pentadienyl cation structure of 19 is emphasized, and in analogy to the gold-catalyzed Rautenstrauch rearrangement [10] a ring closure to the allyl cation 20 could follow. Here the allyl cation in 20 would be part of a well-stabilized benzylic cation.…”

Gold and Platinum Catalysis of Enyne Cycloisomerization

“…In 2005, Toste and co-workers reported that cationic phosphine-gold(I) complexes are effective catalysts for this process, which also enabled the construction of enantiomerically enriched cyclopentenes. [53] The study of the initial scope of the process is depicted in Scheme 72. The reaction exhibited a broad substrate scope, including terminal and internal alkynes, as well as di-and trisubstituted alkenes, which enabled construction of bicyclic and tricyclic enones.…”

Ruthenium vinyl carbene intermediates in enyne metathesis

“…Similar rearrangements have been used by others in related metal-catalyzed pi bond reorganizations. [79][80][81] Murai's catalyst promotes vinyl carbene formation from propargylic esters and leads to cyclopropanation of an alkene (Scheme 36). The resulting cyclopropanes 92 are obtained with modest selectivities (2.3-6:1 ratio) cis/trans.…”