Ferric Chloride Hexahydrate‐Catalyzed Highly Regio‐ and Stereoselective Conjugate Addition Reaction of 2,3‐Allenoates with Grignard Reagents: An Efficient Synthesis of β,γ‐Alkenoates

Abstract

Ferric chloride hexahydrate was shown to be an efficient catalyst for the conjugate addition of 2,3-allenoates with alkyl-, aryl-, or vinyl-Grignard reagents to synthesize polysubstituted b,g-unsaturated alkenoates with high regio-and stereoselectivity. The in situ formed magnesium dienolate may readily react with different electrophilic reagents under different reaction conditions with or without a catalyst to construct an allylic quaternary carbon at the a-position of the ester group and a stereocontrollable retention of the carbon-carbon double bond.

Ti-Catalyzed Radical Alkylation of Secondary and Tertiary Alkyl Chlorides Using Michael Acceptors

“…Alternative approaches to accessing the same type of products from alkyl chlorides frequently entail the generation of corresponding Grignard reagents followed by Michael addition 31 or Sn-mediated radical processes, 19a the latter of which are often carried out in an intramolecular fashion to avoid competitive hydrogen atom transfer (HAT) and other side reactions. Our Ti-catalyzed reaction thus provides an alternative platform for accessing these products with significantly improved ease of operation, substrate scope, and selectivity.…”

Metal-Catalyzed Intermolecular Hydrofunctionalization of Allenes: Easy Access to Allylic Structures via the Selective Formation of C–N, C–C, and C–O Bonds

“…1). 171,172 Five years after, the same team developed a reaction catalyzed by CuCl with tetrasubstituted allenes (Scheme 78, eq. 2).…”

A Practical Solution to Stereodefined Tetrasubstituted Olefins

“…On the other hand, the chemistry of alkenolate-type anions has been well established for efficient formations of covalent chemical bonds, while that of conjugated alkadienolate-type anions has not been well developed due to the intrinsic issues of regio- and stereoselectivity: the reaction with a proton may yield the α- [M = Sm, Li, − Mg, , CuLi], γ- [M = n -Bu 4 N], or α-/γ-mixed [M = Li] protonated products (Scheme b). In all these reported cases except for the conjugate addition of 2,3-alkadienoates with Grignard reagents affording the α-protonation products, , the issue of stereoselectivity referring to the carbon–carbon double bonds in the products has not been addressed. Here we show that the conjugate addition of readily available 2,3-allenals , with organozincs (R 2 Zn), which have been produced in large scales in industry, upon deliberate tuning of protonation surprisingly delivered, via formal γ-protonation, stereodefined tetrasubstituted olefins with a very versatile conjugated aldehyde functionality (Scheme c).…”

“…On the other hand, the chemistry of alkenolate-type anions has been well established for efficient formations of covalent chemical bonds, while that of conjugated alkadienolate-type anions has not been well developed due to the intrinsic issues of regio- and stereoselectivity: the reaction with a proton may yield the α- [M = Sm, Li, − Mg, , CuLi], γ- [M = n -Bu 4 N], or α-/γ-mixed [M = Li] protonated products (Scheme b). In all these reported cases except for the conjugate addition of 2,3-alkadienoates with Grignard reagents affording the α-protonation products, , the issue of stereoselectivity referring to the carbon–carbon double bonds in the products has not been addressed.…”

“…The final product 2 was then formed exclusively via the concerted intramolecular 1,5-hydride transfer of (1 Z ,3 E )- 7 or (1 Z ,3 Z )- 7 (Scheme ). It is interesting to note that in the literature it has been noted that the rate of α-protonation is much faster than that of γ-protonation, so that the reaction quenched with proton yields mostly the α-protonated products …”