Simple Synthetic Transformations of Highly Enantio‐Enriched 4‐Alkyl‐2,5,7‐cyclooctatrienols into Functionalized Bicyclo[4.2.0]octa‐2,4‐dienes and 2,6‐Cyclooctadienones

Abstract

4‐Alkyl‐2,5,7‐cyclooctatrienols with high enantiomeric purities (93−96% ee), obtained by an improved copper‐phosphoramidite‐catalyzed addition of dialkylzinc reagents to cyclooctatetraene monoepoxide, have been subjected to simple and practical manipulations. Simple esterification reactions are able to deliver new functionalized isomeric 8‐alkyl‐7‐acyloxybicyclo[4.2.0]octa‐2,4‐dienes through a domino sequence of rearrangement reactions, in good yields. Moreover, new 4‐alkyl‐substituted‐2,6‐cyclooctadienones with high optical purity can be efficiently obtained from gram‐scale reactions by simple thermal treatment. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Understanding the Torquoselectivity in 8π-Electrocyclic Cascade Reactions: Synthesis of Fenestradienes versus Cyclooctatrienes

“…1970, 35, 1900-1904 In those experiments trienyne 4a was prepared through classical Sonogashira coupling (5% Pd(PPh 3 ) 4 , CuI 15%, Et 3 N, MeCN). The cascade reaction was always capricious, but in several cases afforded cyclized materials 21a in 36-93% yields (entries [11][12][13][14][15]. When trienyne 4a was prepared through a modified Sonogashira protocol starting from the silylated alkyne (1.2 equiv of ICH ) CHC(Me) 2 OH, MeCN/Et 3 N 8:2, RT, 13 h, 2 equiv of CuCl), 28 the partial hydrogenation was totally ineffective (entry 10).…”

“…Such 8π−6π-electrocyclization cascades were elegantly used for the total synthesis of several natural products . A similar 8π−6π-cascade strategy was used for the syntheses of elysiapyrones A and B, coprinolone, vitamin A, functionalized bicyclo[4.2.0]octadienes, and bicyclo[4.2.0]octenones . Owing to the fast conversion of b to c , there are almost no natural products containing a cyclooctatriene system.…”

Asymmetric Ring‐Opening of Epoxides and Aziridines with Carbon Nucleophiles

“…Moreover, ring‐contraction isomerization to the seven‐membered trienyl carboxaldehyde, which, in turn, adds to the organometallic reagents to give substituted cycloheptatrienyl alcohols, is the most common reaction observed when organometallic reagents are employed with this substrate 76. Our catalytic system allowed a highly enantioselective desymmetrization of COT‐monoepoxide with dialkylzinc reagents and the corresponding trienyl alcohol addition product 23 was obtained with a high yield, complete conjugated regioselectivity, and high enantioselectivities 77,78…”

Two Steps to Bicyclo[4.2.0]octadienes from Cyclooctatetraene: Total Synthesis of Kingianic Acid A

“…We recently disclosed an overall anti-vicinal difunctionalization of cyclooctatetraene (COT) through epoxidation and anti- S N 2′ addition/ring opening followed by Claisen rearrangement, thereby intercepting the 8π/6π cascade at its midpoint, culminating in the total synthesis of endiandric acid J and beilcyclone A (Figure a) …”

“…Literature precedents for organocuprate additions to activated vinylcyclopropane substrates are scarce and somewhat discouraging, with the simplest substrate shown to proceed with predominantly 1,7 rather than 1,5 selectivity (Figure c) and more structurally complex substrates proceeding with either 1,7 or 1,5 selectivity . The structurally relevant substitution/ring opening of cyclooctatetraene oxide proceeds with anti- S N 2′ selectivity (Figure a), whereas other cyclic alkenyl oxiranes give mixtures of S N 2 and S N 2′ products …”