Studies on the Synthesis of Macrocyclic Allenes by Ring Closing Metathesis and Doering–Moore–Skattebøl Reaction

Abstract

Several efficient synthetic approaches to allenic cyclophanes of the general structure 2/3, which are of interest as chiral ligands or host molecules, are described. The combination of the ruthenium‐catalyzed ring‐closing metathesis and the Doering–Moore–Skattebøl (DMS) reaction using the Seyferth reagent PhHgCBr3 provided a straightforward access to the allenic cyclophane 8. The macrocycles 13 and 17 with the allenic bridge between the aromatic units were also obtained efficiently by copper‐promoted SN2'‐substitution of propargylic acetates and ring‐closing metathesis. Alternatively, macrocyclic allenes can be synthesized by ring‐closing metathesis of α,ω‐bisallenes, as was demonstrated by the formation of the products 20, 21, and 23. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Transition metals in organic synthesis: Highlights for the year 2005

“…A large variety of ring systems were prepared via alkene-alkene RCM using ruthenium catalysts [441] including, furans and pyrroles [1062], macrocycles [1063][1064][1065][1066][1067][1068][1069][1070][1071], five-to nine-membered unsaturated cyclic amines [498,519,898,[1072][1073][1074][1075][1076][1077], cyclooctenes [1078], chiral azepin-3-ols and azocin-3-ols [1079], oxepinand oxocin-annulated 2-quinolones [1080], benzazepines [1081,1082], 1-azaspiro [5.5]undacanes [1083], N-sulfonyl-2-quinolinones [1084], bis(silyl)- [3]-ferrocenophanes [1085], ferroceno-quinolines and -isoquinolines [1086], polycyclic hydrocarbons [1087], cyclic ␣-arylthiophosphonate esters [1088], carbohydrate-based macrolides [1089], fused carbazoles [157], 4-methyl-5-alkyl-2(5H)-furanones [1090], bibicyclo [8.8.8]hexacosanes [1091], bicyclic imidazoles [1092], bicyclic phosphates [1093], bicyclic lactams [1094], hexofuranose-like imino sugars [1095], C8-glycomimeti...…”

Cyclization reactions of bis(allenes) for the synthesis of polycarbo(hetero)cycles

“…Thus, during the studies of ring closing metathesis (RCM) between alkenes and allenes in order to obtain 20 cyclophanes, the synthesis of allenic macrocycles by treatment of α,γ-bis(allenes) 154 and 155 with Grubbs´first generation catalyst under high dilution conditions was reported (Scheme 56). 53 Thus, the desired 15-and 17-membered allenes 156 were isolated in reasonable yields. However, the analogous 25 bis(allene) bearing an aromatic speacer afforded allenic cyclophane 157 with only 9% yield.…”

The first transannular [4+3] cycloaddition reaction: synthesis of the ABCD ring structure of cortistatins

“…In addition, nitrogen-stabilized oxyallyl cations can be generated in situ via epoxidations of allenamides, which can undergo inter- and intramolecular [4+3] cycloadditions with dienes 12–14. Considering the advances in the chemistry of ring closing metathesis (RCM),15,16 and a report from Janssen and Krause on allene RCM reactions,17 the allene function was chosen as the functional equivalent to an allyl cation in our initial plan.…”

“…Our initial plan was to generate the corresponding macrocyclic furanoalkene followed by the addition of a dihalocarbene to the double bond and then base mediated allene formation 17. This plan started with the reaction between the lithiated furan and the commercially available 1,2-epoxy-5-hexene, Scheme 2, to generate the alcohol 4 .…”

“…We turned our attention to preparing the allene function directly and form the macrocyclic allene using an allene RCM reaction, Scheme 3 17. This plan started with the known monoalkylated furan 10 ,20 which was lithiated and alkylated with 2-(4-Bromo-butoxy)-tetrahydropyran to give the bis THP ether 11 .…”