Iron-Catalyzed Highly Regio- and Stereoselective Conjugate Addition of 2,3-Allenoates with Grignard Reagents

Abstract

An efficient highly regio- and stereoselective iron-catalyzed conjugate addition of 2,3-allenoates with primary or secondary alkyl, phenyl, or vinyl Grignard reagents to synthesize multi-substituted beta,gamma-unsaturated enoates has been reported. The in situ formed magnesium dienolate may readily react with different electrophilic reagents to construct an allylic quaternary carbon at the alpha-position of the ester group.

Iron Catalysis in Organic Synthesis

“…Ma and co-workers described the Fe(acac) 3 -catalyzed carbometalation of 2,3-allenoates which after hydrolysis afforded β,γ-unsaturated esters under very mild conditions (Scheme 388). 687 The reaction proceeded with high regio-and stereoselectivity and provided the trisubstituted olefins in high yields. The feasibility of trapping the intermediate magnesium dienolate with other electrophiles was proven by reaction with acrolein, acetyl chloride, and methyl chloroformate.…”

Stereoselective Synthesis of Tri‐ and Tetrasubstituted Alkenes by Iron‐Catalyzed Carbometalation Ring‐Opening Reactions of Cyclopropenes

“…For example, Michael addition or alkylation of the ring-opened products was accomplished efficiently without compromising the integrity of the alkene [Eq. (6) and Eq. (7)].…”

“…This process leads to b,g-unsaturated ester building blocks, which can be difficult to prepare using alternative methods owing to possible migration of the alkene into conjugation. [6] Owing to their highly strained nature, cyclopropenes exhibit a diverse range of reactivities, which present unique opportunities for organic synthesis. [7] Although cyclopropenes are susceptible to a range of useful carbometalation (and hydrometalation) reactions, [7,8] a significant majority of examples described to date result in preservation of the threemembered ring to provide highly functionalized cyclopro-panes (Scheme 1, left).…”

“…[11,12] Under optimized conditions, cyclopropenes 1 a-1 h [13] reacted smoothly to provide a variety of trisubstituted alkenes 2 a-2 r in good to excellent yields with high stereoselectivities (> 19:1) ( Table 1). [6] Tolerated functionality at C3 encompassed a range of esters and a phenylsulfone, while both alkyl and aromatic substitution at the cyclopropene C=C bond were permitted. Regarding the scope of the organometallic reagent, trialkylaluminum moieties ranging from linear Scheme 1.…”

Recent advances in transition-metal-catalyzed intermolecular carbomagnesiation and carbozincation

“…Ma reported that treatment of a 2,3-allenoate with methylmagnesium reagent in the presence of a catalytic amount of iron catalyst exclusively gave the corresponding product 5e (Scheme 47) [134]. Not only primary alkylmagnesium reagents but also secondary alkyl-, phenyl-, and vinylmagnesium reagents could be employed.…”