Asymmetric allylic alkylation of Morita–Baylis–Hillman carbonates with α-fluoro-β-keto esters

Abstract

SummaryIn the presence of a commercially available Cinchona alkaloid as catalyst, the asymmetric allylic alkylation of Morita–Baylis–Hillman carbonates, with α-fluoro-β-keto esters as nucleophiles, have been successfully developed. A series of important fluorinated adducts, with chiral quaternary carbon centres containing a fluorine atom, was achieved in good yields (up to 93%), with good to excellent enantioselectivities (up to 96% ee) and moderate diastereoselectivities (up to 4:1 dr).

Modern Approaches for Asymmetric Construction of Carbon–Fluorine Quaternary Stereogenic Centers: Synthetic Challenges and Pharmaceutical Needs

“…Asymmetric allylic alkylation represents another efficient strategy for the preparation of chiral α -allyl- α -fluoro carbonyl compounds bearing a quaternary stereogenic C–F center (Scheme 92). 269 Tan, Jiang, and co-authors reported in 2013 an asymmetric allylic alkylation reaction of linear α -fluoro- β -keto-esters 238 by using (DHQD) 2 PHAL 69 as organocatalyst. The reaction used Morita-Baylis-Hillman carbonates 239 as electrophilic reagents and afforded the corresponding allylic alkylated product 240 in good chemical yields, good enantilselectivities, and moderate diastereoselectivities.…”

Synthesis of Multifunctional α,α‐Difluoroketones through Allylic Alkylation of Difluoroenoxysilanes with MBH Carbonates

“…For instance, the trifluoromethyl(thiol)ations of MBH carbonates 2 with TMSCF 3 or Zard's trifluoromethylthiolation reagent have been independently presented by the groups of Shibata, [19a] Jiang, [19b] Shi, [19c] and Cahard [19d] . The organocatalytic allylic monofluoroalkylations of 2 with fluoromethyl(bisphenylsulfones), [19e,f] 2‐fluoromalonates, [19h] or α‐fluoro‐β‐keto esters [19i] have also been explored by the groups of Shibata, Jiang, and Rios. In addition, Han, Soloshonok, Hayashi developed a palladium‐catalysed asymmetric allylic alkylation of 3‐fluorooxindole derived Colby pro‐enolates with MBH carbonates [19j] .…”

Enantioselective Organocatalyzed Transformations of β-Ketoesters

“…185 Organocatalytic methods utilizing Morita−Baylis−Hillman (MBH) adducts in asymmetric allylic alkylation (AAA) reactions have become popular due to their importance for the construction of carbon−carbon quaternary stereocenters. 267 In 2013, Jiang and Tan's team 268 reported the first alkylation on an allylic substrate with α-fluoro-β-ketoester with Morita−Baylis− Hillman carbonates in the presence of several commercially available cinchona alkaloid catalysts. Commercially available (DHQD) 2 PHAL (68) 269 proved to be a satisfactory option providing the product in mesitylene as the optimized solvent.…”