Iridium‐Catalyzed Regio‐ and Enantioselective Allylic Substitution of Trisubstituted Allylic Electrophiles

Abstract

The first Ir-catalyzed enantioselective allylation of trisubstituted allylic electrophiles has been developed. Through modification of the leaving group of allylic electrophiles, we found that trisubstituted allylic phosphates are suitable electrophiles for asymmetric allylation. The reaction of allylic phosphates with enol silanes derived from dioxinones gave allylated products in good yields with high enantioselectivities.

Enantioselective Synthesis of Acyclic α‐Quaternary Carboxylic Acid Derivatives through Iridium‐Catalyzed Allylic Alkylation

“…However, the success of this strategy hinged upon the implementation of a trisubstituted allylic electrophile, which was predicted to be unreactive in an enantioselective iridium‐catalyzed allylic alkylation reaction. It is known that the reaction rates of these processes decrease with increasing substitution on the olefin of the electrophile . In this work, we unlocked this heretofore unreactive class of electrophiles to achieve the first example of an enantioselective iridium‐catalyzed allylic alkylation reaction to form a quaternary stereocenter at the allylic position.…”

New Developments of the Principle of Vinylogy as Applied to π-Extended Enolate-Type Donor Systems

“…A catalytic, enantioselective, Ir-catalyzed vinylogous allylic alkylation of trisubstituted allylic electrophiles such as allylic phosphates 783 with dioxinone-derived dienoxysilanes 782 was developed by Hartwig and Chen in 2016 ( Scheme 199 ). 513 By surveying different leaving groups within allylic electrophiles, the authors found that trisubstituted allylic phosphates 783 were suitable electrophiles for asymmetric allylation promoted by the Ir/phosphoramidite ligand L27 system, affording the corresponding branched allylated products 784 in good yields (up to 90%) and high stereoselectivity (12:1 to 20:1 branched vs linear; 5.1 to 8.1 γ vs α; up to 98% ee).…”

Iridium-catalyzed enantioselective direct vinylogous allylic alkylation of coumarins

“… 6 Despite these developments during the past two decades, the use of vinylogous nucleophiles in Ir-catalyzed asymmetric allylic alkylation (AAA) has received much less attention and only a handful of reports exist ( Scheme 2A ). 7 – 9 …”

“…In 2014, Hartwig et al reported the first application of a vinylogous nucleophile, namely preformed silyl dienolates, in Ir-catalyzed AAA. 7 The Jørgensen group combined the concept of dienamine activation with Ir-catalyzed AAA for regio-, diastereo- and enantioselective γ-allylic alkylation of α,β-unsaturated aldehydes. 8 More recently, the Stoltz group developed a formal enantioselective γ-allylic alkylation of α,β-unsaturated malonates through a sequential Ir-catalyzed AAA/Cope rearrangement.…”