Stabilized Arylzinc Iodides in Negishi Acylative Cross-Coupling: A Modular Synthesis of Chalcones

Abstract: Stabilized arylzinc iodides, synthesized by direct insertion of zinc into the corresponding halides, were used as nucleophiles into an acylative Negishi coupling reaction to synthesize chalcones. The reaction conditions were optimized to afford optimal results on a model reaction and then applied to synthesize nine compounds. Esters, chlorides, electron-rich, electron-poor and sterically hindered substrates are well tolerated and even heteroaryl derivatives can be synthesized

Identification and synthesis of new sex-specific components of olive fruit fly (Bactrocera oleae) female rectal gland, through original Negishi reactions on supported catalysts

In the present study, eleven new sex-specific components extracted from female rectal gland of olive fruit flies were synthesized and identified. The quantitative determination of those components by GC and GC/EI-MS, at different moments of the insect life span, highlighted the growing trend of their secretion. While for the synthesis of saturated esters, conventional transesterification methods could be adopted, for the synthesis of unsaturated components, a Negishi cross-coupling between organozinc halides and (Z)-1-bromo-1-alkenes was developed. To the extent of our knowledge, this reaction represents the first example of supported-catalyst promoted Negishi coupling, between an alkylzinc reagent and an alkenyl halide

Nuovi metodi di preparazione di organozinco alogenuri via metallazione ossidativa e loro impiego nella sintesi di calconi tramite reazioni di Negishi acilative.

La sintesi di calconi con metodologie semplici, versatili, ecocompatibili ed accettabili su grande scala, rappresenta un problema ancora aperto nonostante l’evidente interesse applicativo e farmaceutico di questa classe di composti a cui appartengono numerose sostanze naturali bioattive. Nel presente lavoro sono stati messi a punto nuovi ed originali protocolli per la sintesi di organozinco alogenuri; in particolare è stato individuato ed ottimizzato un metodo veloce, pratico e green per preparare arilzinco alogenuri da ioduri arilici elettronricchi via metallazione ossidativa, seguendo una procedura senza precedenti. Una volta ottenuto questo primo risultato, gli arilzinco alogenuri così prodotti, sono stati impiegati in reazioni di Negishi acilative con cinnamoil cloruri. Per quanto le specie organozinco così ottenute siano risultate meno reattive di arilzinco alogenuri preparati in modi più convenzionali, dopo una messa a punto delle condizioni sperimentali, in particolar modo relativamente al solvente e al catalizzatore, è stato individuato un protocollo semplice e conveniente che permette rese elevate nella sintesi di calconi da cloruri cinnamici e arilzinco ioduri

New protocols for the chemo-, regio- and stereoselective formation of C - C bonds via organometallics also by using innovative synthetic techniques

The purpose of this project has been to disclose the yet unexplored potential of organometallics to make new C-C bonds with selectivity. A particular attention has been paid to organozinc halides and to the use of new synthetic tools, in particular, to the use of water and surfactants as the reaction solvent. The procedures developed have been prompted by the need for simple methods, with potential industrial applicability, and in agreement with the principles of the green chemistry as much as possible

Enantioselective conjugate addition of stabilized arylzinc halides to enones

The enantioselective addition of organometallic compounds is particularly important in the field of the total synthesis of natural products. Several organometallics have been used for this purpose but, except for some seminal works, the enantioselective addition of organozinc halides to enones remains undeveloped with respect to the reaction of other organometallics like, for example, organoboron. A few examples of this chemistry with organozinc halides have been reported and, in all cases, the organometallics used in the addition have been made by transmetalation from highly reactive organolithium species. This latter aspect limits the application of the reaction from the point of view of functional group tolerance, environmental friendliness, and general usability. We developed an enantioselective conjugate addition protocol of organozinc halides to enones, both cyclic and linear. The organozinc reagents employed in our protocol have been made by direct insertion of zinc metal into organic halides and have been stabilized with TMEDA to improve the functional group tolerance. Yields and enantiomeric excess are good to excellent and the protocol has general applicability

Preparation of arylzinc halides by silver promoted oxidative metalation

Organozinc halides are useful reagents for organic synthesis, as witnessed by their wide use as nucleophiles in the Negishi coupling, a powerful and versatile reaction for carbon-carbon bond formation. Direct insertion of zinc metal into organic halides provides the most practical and atom-economical way for preparing these organometallic reagents. Nevertheless, oxidative metalation often has limited application due to long reaction times required by many substrates. We found that a catalytic amount of silver acetate efficiently promotes direct insertion of zinc metal to aryl iodides, having different structure, in ethereal solvent. Also electron-rich substrates rapidly undergo oxidative metalation. Arylzinc iodides thus formed give Negishi coupling products under mild reaction conditions. In all cases, reaction times required to provide full conversion in the metalation step are between 2 and 15 hours even on electron-rich substrates, which are scarcely reactive under the most commonly used reaction conditions

ARYLZINC HALIDES BY SILVER CATALYZED ZINC INSERTION TO ARYL IODIDES

We found that a catalytic amount of silver acetate efficiently promotes direct insertion of zinc metal to aryl iodides, having different structure, in ethereal solvent. Also electron-rich substrates rapidly undergo oxidative metalation. Arylzinc iodides thus formed give Negishi coupling products under mild reaction conditions. In all cases, reaction times required to provide full conversion in the metalation step are between 2 and 15 hours even on electron-rich substrates, which are scarcely reactive under the most commonly used reaction conditions

Uncatalyzed conjugate addition of organozinc halides to enones in DME: a combined experimental/computational study on the role of the solvent and the reaction mechanism

The reaction mechanism of a new conjugate addition reaction of organozinc halides to enones is disclosed by a combined experimental/computational study