Palladium‐Catalyzed Oligocyclizations of 2‐Bromoalk‐1‐ene‐(n+1),(m+n+1)‐diynes – Influence of Tether Lengths and Substituents on the Outcome of the Reaction (Part I)

Abstract

The outcomes and the mechanistic pathways of the palladium-catalyzed Heck-type cascade oligocyclizations of various 2-bromoalkenediynes were explored with respect to the lengths of the tethers between the multiple bonds and the nature of the substituent at the acetylenic terminus. Just like substrates containing two three-atom tethers, 2-bromotridec-1-ene-6,13-diynes 10a,b with one three-and one four-atom tether undergo two consecutive intramolecular 5-and 6-exodig carbopalladations with subsequent 6π-electrocyclization and β-hydride elimination to form tricycles 35a,b with a central benzene ring in 67 and 61 % yield, respectively, independent of the fact that 10a contains an electron donor and 10b an electron acceptor at the acetylene terminus. However, when 2-bromotetradec-1-ene-7,13-diynes 22, 29 on one side and 16, 27, 31 on the other are subjected to Heck reaction conditions, tricycles with a central benzene ring are formed only, when the substituent at the acetylene terminus is not a

Palladium‐Catalyzed Cascade Oligocyclizations Involving Competing Elementary Steps Such as Thermal [1,5]‐Acyl Shifts

“…afforded the tricyclic systems 13 1 ) and 14 1 ), each with a bisfused benzene ring in 42 and 75% yield, respectively (for a preliminary communication of these results, see [6]) (Scheme 4). As was previously reported [4], the Pd-catalyzed oligocyclizations of 2-bromotetradec-1-ene-7,13-diynes like 4 with two four-atom tethers between each pair of multiple bonds, but bearing an electron-withdrawing COOMe group at the acetylene terminus, led to tetracyclic systems of type 15. In contrast, the bromoalkenediyne 4 with a terminal Ac group, upon treatment with a Pd precatalyst typically employed for Heck reactions, unexpectedly, furnished the tricyclic compounds 16 and 17 in 25 and 15% yield, respectively, and none of the tetracycle 15, despite the electron-withdrawing nature of the Ac group (Scheme 5).…”

“…As we previously reported [4], the results of the Pd-catalyzed intramolecular oligocyclization of various 2-bromoalk-1-ene-7,13-diyne substrates initially leading to the formation of two six-membered rings, are highly affected by the lengths of the tethers between each two multiple bonds and the nature of the substituent at the acetylene terminus. As some of these oligocyclizations are followed by the formation of a bis-annulated cyclopentadiene system, [1,5]-sigmatropic rearrangements might become feasible subsequent processes for substrates bearing a terminal group with a high migratory aptitude such as an Ac group or an H-atom.…”

“…As was previously reported [4], 2-bromoalkenediyne substrates containing at least one three-atom tether leading to a five-membered ring will undergo, after the oxidative addition step, two consecutive 5-exo-dig and n-exo-dig carbopalladations followed by 6p-electrocyclization and b-hydride elimination to furnish tricyclic bis-annulated benzene derivatives such as 13 and 14 (Scheme 4). On the other hand, substrates having tethers longer than three atoms will undergo Pd-catalyzed oligocyclization cascades in which 5-exo-trig carbopalladations instead of 6p-electrocyclizations take part as the fourth step.…”

“…The bis-cyclohexane-annulated benzene derivatives 17 and 19 are formed by cyclopropylmethyl-to homoallylpalladium rearrangement with cleavage of the inner cyclopropyl bond in the intermediates of type 25 and subsequent b-dehydropalladation [4].…”

“…-The substrates used in this study were prepared following the same synthetic routes described earlier for the synthesis of 2-bromotridec-1-ene-6,12-diynes and 2-bromotetradec-1-ene-7,13-diyne derivatives [4]. Thus, a substrate with one three-atom and one four-atom tether between the 2-bromoene and the central C C bond and between the latter and the terminal C C bond, respectively, was obtained from 1 [4] by installing the Ac group at the acetylene terminus by deprotonation with BuLi at À 788 and treatment of the resulting lithium acetylide with Ac 2 O to furnish diethyl 2-(2-bromoprop-2-en-1-yl)-2-(4-methoxy-10-oxoundeca-2,8-diyn-1-yl)propanedioate (2) in 68% yield (Scheme 1).…”