Regioselective Preparation of Functionalized exo‐Methylene‐ cyclopentanes and exo‐Methylenepyrrolidines via Silaborative Carbocyclization of 1,6‐Enynes

Abstract

Silaborative carbocyclization of 1,6-enynes catalyzed by Pd-PEPPSI-IPr {PEPPSI = pyridine-enhanced precatalyst preparation stabilization and initiation; IPr = N,N-bisA C H T U N G T R E N N U N G [2,6-(diisopropyl)phenyl]imidazolium} employing either (dimethylphenylsilyl)pinacolborane or (chlorodimethylsilyl)pinacolborane provides access to densely functionalized five-membered rings as single diastereomers in excellent yields. The vinylboronate functions were employed in palladium-catalyzed Suzuki cross-coupling reactions with a range of aryl bromides, containing electron-withdrawing as well as electron-donating substituents, furnishing arylated exo-methylenecyclopentanes or exo-methylenepyrrolidines in good yields. Subsequent oxidation of the isopropoxydimethylsilyl function generated via addition of (chlorodimethylsilyl)-pinacolborane provided access to hydroxymethyl derivatives of the arylated compounds. Use of a chiral ester, bismenthyl (2-propenyl)(2-propynyl)malonate, afforded two diastereomeric products which could be separated, thereby giving access to the cyclized compounds as single isomers, with opposite absolute configurations at the newly formed stereocenter.

Cobalt-Catalyzed Hydrosilylation/Cyclization of 1,6-Enynes

“…The insertion reaction of an alkyne to the cobalt–hydride bond afforded the vinyl cobalt species followed by insertion of an alkene to give the alkyl-cobalt species which could react with the silane to regenerate the cobalt hydride species and afford the product. It should be noted that the configuration of alkenes is opposite to that in products obtained by silaboration/cross-coupling reactions of 1,6-enynes containing a terminal enyne with aryl halides …”

Diastereodivergent Hydrosilylative Enyne Cyclization Catalyzed by N‐Heterocyclic Carbene‐Ni(0)†

“…[ 1‐4 ] Notable methodologies have been developed over the years to utilize those silylated products, in which Hiyama coupling [ 5‐9 ] and Fleming‐Tamao oxidations are often exploited. [ 10‐12 ] In particular, the catalytic hydrosilylative enyne cyclizations have received a lot of attention over decades and efficiently construct various carbo‐/hetero‐cycles (Scheme 1a). [ 13‐15 ] Unlike the hydrosilylative diyne cyclization, most of the enyne mechanisms' first step is the corresponding metal hydride or metal silyl insertions to the alkyne rather than metalacycle formation.…”

Borylative Cyclization Reactions

“…Moberg and co‐workers reported the regioselective preparation of densely functionalized five‐membered‐ring compounds – exo ‐methylenecyclopentanes and exo ‐methylenepyrrolidines – as single diastereomers in excellent yields through silaborative carbocyclization, catalyzed by Pd‐PEPPSI‐IPr, of 1,6‐enynes containing terminal alkene and alkyne groups, in the presence of (dimethylphenylsilyl)‐ or (chlorodimethylsilyl)pinacolborane (Scheme ) . In the latter case the cyclization products were sensitive to moisture, so they were converted into the isopropyl derivatives, which were stable to chromatography, by treatment with i ‐PrOH and pyridine (Scheme ).…”