Stereoselective Cross‐Coupling of Grignard Reagents and Conjugated Dienylbromides using Iron Salts with Magnesium Alkoxides

Abstract

A convenient procedure allowing iron‐catalyzed cross‐coupling of alkyl or aryl Grignard reagents and conjugated dienyl bromides is reported, relying on the use of cheap and non‐toxic magnesium alkoxides as sole additives. An excellent stereoselectivity is observed in the alkyl‐dienyl series. This sequence has been applied to the synthesis of the sex pheromone of codling moth, illustrating its applicability for obtaining targets of industrial interest. Preliminary mechanistic studies carried out on the aryl‐dienyl cross‐coupling suggest that in situ generated ate homoleptic organoiron(II) species act as catalytically relevant intermediates. A modified preparative method for the realization of THF solutions of dienyl bromides as “ready‐to‐use” coupling partners is also discussed, circumventing the thermal instability of those derivatives.

The molecular-level effect of alkoxide additives in iron-catalyzed Kumada cross-coupling with simple ferric salts

“…Analogous to the reactions with alkyl Grignard reagents, reactions with aryl Grignard reagents were also proved to be enhanced in the presence of EtOMgBr. 21 From a molecular standpoint, trends similar to that observed in alkyl ferrous series were obtained regarding the interaction of aryl-ligated ate-[FeAr 3 ] À complexes with EtOMgX salts (X = Cl, Br). It should be noted that the halogen in the in-house generated alkoxide salts switched from X = Cl for the alkyl Grignard reagents to X = Br for the aryl Grignard reagents due to reagents being more readily accessible for the high purity NMR experiments.…”

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

“…As a representative target, we developed the total synthesis of the codling moth sex pheromone, (8 E ,10 E )-dodecadien-1-ol ( 4 ), featuring the introduction of the C 7 –C 8 linkage by a key iron-mediated cross-coupling sequence between the suitable α,ω-difunctionalized Grignard reagent and 1-bromopenta-1,3-diene as the electrophile ( Scheme 6 ) [ 32 ].…”

“…This method can also be used for the alkylation of dienyl bromides by classic aliphatic or aromatic Grignard reagents which do not bear ω-magnesium alkoxide functionalities: in that case, EtOMgX can be used as an external additive to enhance the cross-coupling selectivity, in line with the alkyl–alkenyl and aryl–alkenyl cross-coupling methods discussed earlier ( Scheme 5 ) [ 32 ].…”

Recent advances in the synthesis of insect pheromones: an overview from 2013 to 2022

“…): 42 , 47 Plutella xylostella (Lep., Plutellidae): 43 , 48 Trichoplusia ni (Lep., Noctuidae): 44 , 49 Tortrix viridana (Lep., Tortricidae): 45 , 50 Grapholita molesta , G. funebrana , and Hedya nubiferana (Lep., Tortricidae): ( E )- and ( Z )- 46 , 51 Plutella xylostella (Lep., Plutellidae): 47 , 52 moth (Lep.) 48–52 , 47 Keiferia lycopersicella (Lep., Gelechiidae): 53 , 53 Anthistarcha binocularis (Lep., Gelechiidae): 54 and 55 , 54 Illiberis pruni (Lep., Zygaenidae): 56 and 57 , 55 Rhyacionia buoliana (Lep., Tortricidae): 58 , 50 Phyllonorycter blancardella (Lep., Gracillariidae): ( Z )- 59 , 56 Ostrinia furnacalis (Lep., Crambidae): ( E )- and ( Z )- 60 , 57 Melanotus communis (Col., Elateridae): 61 , 58 Dasineura pyri (Dip., Cecidomyiidae): 62 , 59 Ithomia salapia (Lep., Nymphalidae): 63 and 64 , 60 Cydia pomonella (Lep., Tortricidae): 65 , 61,62 Stathmopoda masinissa (Lep., Stathmopodidae): 66 and 67 , 63 Lobesia botrana (Lep., Tortricidae): 68 , 64–66 Malacosoma neustria and Dendrolimus punctatus (Lep., Lasiocampidae): 69 , Spodoptera littoralis and S. litura (Lep., Noctuidae): 70 , 67 Thaumetopoea bonjeani (Lep., Notodontidae): 71 and 72 , 68 Acanthoscelides obtectus (Col., Chrysomelidae): 73 , 69 Plodia interpunctella hb. (Lep., Pyralidae): 74 , 70 Pectinophora gossypiella (Lep., Gelechiidae): 75 , 29,71 Spodoptera exigua (Lep., Noctuidae): 76 , 72 Phyllonorycter ringoniella (Lep., Gracillariidae): 77 , 73,74 Loepa sakaei (Lep., Saturniinae): 78 , 75 Symmetrischema tangolias (Lep., Gelechiidae): 79 , 76 Tuta absoluta (Lep., Gelechiidae):…”