Tandem Reaction of Enynyl Acetate: Precursor of Allenyl Ketones

Abstract

Deacetylation of enynyl acetates under basic conditions allows convenient access to reactive allenyl ketones, which can then undergo 1,4-addition of nucleophiles to furnish β,γ-unsaturated ketones. Benzofuran and indole derivatives have also been obtained from enynyl acetates with an o-hetero-atom-substituted aryl group via intramolecular 1,4-addition.Key words alkyne; allenyl ketone; tandem reaction; enynyl acetate; furan; indole Reactions of functionalized allenes have been investigated in the past two decades.1-8) Among them, α-allenyl carbonyl compounds are important building blocks for a variety of organic transformations. Cycloisomerization of allenyl ketones (Chart 1) in the presence of a transition metal catalyst is an efficient way to build substituted furans.9-16) It was first reported by Marshall and Robinson 9) and later by Hashmi. 11) In 2003, Gevorgyan and colleagues reported copper-catalyzed cycloisomerization of thioallenylketones via 1,2-migration of the thiogroup 17) and later developed a series of metal-catalyzed 1,2-migration/cycloisomerization methodology toward multisubstituted 3-seleno-, 18) acyloxy-, 19) halo-, 20) aryl-, and alkyl-furans. 21) In some of those studies, alkynyl ketones or propargyl ketones were used as precursors of allenylketones, involving propargyl-allenyl isomerization prior to 1,2-migration/cycloisomerization. 13,15,16) During the course of our study on exploration of a new tandem reaction triggered by the reactivity of an alkyne triplebond, we reported multisubstituted furan formation from (E)-or (Z)-enynyl acetates, 22) which were prepared regio-and stereoselectively by Sonogashira coupling reaction of (E)-or (Z)-iodoenyl acetates, obtained from the reaction of alkyne with N-iodosuccinimide (NIS) and acetic acid 23) (Chart 2). Treatment of (E)-enynyl acetates 2 and (Z)-enynyl acetates 3 with NIS afforded multisubstituted furans 5 via the common iodoallenyl ketones 4 regardless of the double-bond geometry of starting enynyl acetate.24) The proposed reaction pathway involves the formation of iodoallenyl ketone 4 by electrophilic addition of NIS to the triple-bond of enynyl acetate followed by 1,2-halogen migration 20) of the resulting iodoallenyl ketone and cycloisomerization.This result encouraged us to explore the possibility of enynyl acetates as precursors of allenyl ketones and application for a new tandem reaction. Hammond and colleagues reported regioselective reactions of alkynyl enolate 25,26) in which alkynyl enolates were generated by deprotonation of allenyl ketone or propargyl ketone. We hypothesized that

2‐(Alkynyl)anilines and Derivatives — Versatile Reagents for Heterocyclic Synthesis

“…A wide variety of catalysts have been described for the preparation of indoles starting from 2‐alkynylanilines. In the first place, synthesis of indoles can be achieved under basic conditions [5–14] . The deprotonation of an NHR 3 group gives an anion 2 , capable of 5‐ endo ‐dig cyclization (Scheme 2).…”

“…Anilines, bearing electron‐withdrawing groups (sulfamide, acyl, carbonate, etc.) on nitrogen, can be cyclized under the action of carbonates [6–9] . The conversion of N ‐unsubstituted anilines needs stronger bases, and the desired indoles can be obtained under the action of potassium hydride [11–13] .…”

Metal-Catalyzed Synthesis and Transformations of β-Haloenol Esters

“…In this regard, a large number of (Z)-and (E)-β-haloenol esters (both chlorides, bromides and iodides) have been successfully coupled with alipahic and aromatic alkynes, 1,3-enynes or propargylic alcohols to generate the corresponding enynyl ester products in high yields and with complete preservation of the C=C bond stereochemistry of the starting olefins (the results obtained in references [60,76,77] are depicted in Scheme 19). The main interest in these Sonogashira-type reactions is that the enynyl ester products can be employed as starting materials for the generation of polysubstituted furans via metal-catalyzed [76,77] or halogen-induced electrophilic cyclization reactions [30,[79][80][81]. Illustrative examples are shown in Scheme 20.…”

“…Illustrative examples are shown in Scheme 20. The main interest in these Sonogashira-type reactions is that the enynyl ester products can be employed as starting materials for the generation of polysubstituted furans via metal-catalyzed [76,77] or halogen-induced electrophilic cyclization reactions [30,[79][80][81]. Illustrative examples are shown in Scheme 20.…”

Stereoselective Approach to Multisubstituted Enolates from Unactivated Alkynes: Oxyalkylidenation of Alkynyl Ketone Enolates with Aldehydes

“…Second, the alkyne substrates are limited to highly activated ones such as ynamides or those bearing an internal oxygen nucleophile. Thus, ordinary alkynes have remained rather unexplored as precursors to stereodefined enolates …”