Stereoselective Preparation of Polyfunctional Cyclopentane Derivatives by Radical Nickel‐ or Palladium‐Catalyzed Carbozincations

Abstract

The reaction of 5-hexenyl iodides with diethylzinc (2 equiv) and catalytic amounts of a Pd" or Ni" complex like PdCl,(dppf), PdCl,(MeCN),, or Ni(acac), results in an efficient ring closure (THF, RT, 2-12h) affording cyclopentylmethylzinc iodides, which, after transmetalation with CuCN.2 LiCI, can be further functionalized by treatment with a range of electrophiles like allylic halides, acyl chlorides, enones, nitroolefins, ethyl propynoate, and alkynyl halides to yield polyfunctional cyclopentane derivatives. The ring closures occur via radical intermediates, and the stereochemistry of the products can be explained according to the rules for radical cyclizations developed by Beckwith. The preparation of several di-and trisubstitut-

New Applications of Polyfunctional Organometallic Compounds in Organic Synthesis

“…Thus, various transition metal catalysts (Pd, [66] Cu, [13] Fe, [67] Co, [67,68] Ti, [69] Ni [70] ) catalyze the reaction of polyfunctional zinc compounds with functionalized electrophiles leading to a broad range of multifunctional organic molecules. Thus, the reaction of 86 with 3-iodo-2-cyclohexenone in the presence of catalytic amounts of Pd 0 provides the protected a-amino-acid 87.…”

“…Thus, the reaction of 86 with 3-iodo-2-cyclohexenone in the presence of catalytic amounts of Pd 0 provides the protected a-amino-acid 87. [70,72] The initial oxidative addition of Pd 0 to the alkyl iodide or alkyl bromide 90 proceeds by a radical mechanism (Scheme 19). With a copper-catalyst (CuCN´2 LiCl), the addition of methyl 2-bromopropiolate [71] leads to the protected acetylene-a-aminoacid 89 (Scheme 18).…”

Radikale und Übergangsmetallkatalyse – eine Allianz par excellence zur Steigerung von Reaktivität und Selektivität in der organischen Chemie

“…Obwohl das Auftreten von Radikalen in verschiedenen übergangsmetallkatalysierten Prozessen wie palladiumkatalysierten Reaktionen, [6] Kharasch-Reaktionen [7] oder nickelkatalysierten Kreuzkupplungen [8] mit der Pd I I-Spezies zum Acylpalladium-Intermediat 6 kuppeln kann. Durch Substitution mit einem Nucleophil wird daraus das Produkt freigesetzt und der Katalysator zurück-gebildet.…”

Carbozincation Reactions of Carbon–Carbon Multiple Bonds

“…29 When the Pd-catalyzed exchange protocol is applied to γ-alkenyliodides, the cyclized organozinc reagents are obtained directly and may be further functionalized. 30 The transmetalation reaction of alkyllithiums or alkylmagnesium halides with zinc salts to provide organozinc species is also a powerful method for the preparation of the carbozincation precursors. 22 These methods are used extensively for the preparation of propargyl/allenylzinc species 31 as well as for the preparation of zinc enolates generated from the corresponding lithium enolates.…”