Nitro-enabled catalytic enantioselective formal umpolung alkenylation of β-ketoesters

Abstract

A formal umpolung strategy is presented for the enantioselective installation of an alkenyl group with a terminal double bond at a tertiary center. This one-pot two-step sequence relies on the unique features of the nitro group, which after inverting the polarity of the alkenylating agent toward the desired bond formation, itself serves as a leaving group.

Bakuchiol – a natural meroterpenoid: structure, isolation, synthesis and functionalization approaches

“…From the synthetic perspective, the stereochemistry is one of the most important feature and the construction of tetra-alkylated carbon stereocenter is the key step in the total synthesis and enantioselective construction of all-carbon quaternary stereocenters itself is considered a challenging task. 48 Moreover, installation of alkenyl groups C(17–18) at sterically hindered positions 49 also make additional level of difficulty in the total synthesis.…”

Asymmetric Conjugate Addition of Phosphonates to Enones Using Cinchona–Diaminomethylenemalononitrile Organocatalysts

“…Flash column chromatography was performed on neutral silica gel (Kanto Silica gel 60N, 40–50 μm). Organocatalysts 1 , 2 , 5 , 6 , 7 , and 8 were prepared by the reported method. α,β-Unsaturated ketones ( 9a – 9m ) were prepared according to the literature procedure. , …”

“…Once the most effective catalyst and solvent had been identified, alternate reaction conditions for the asymmetric conjugate addition were explored (Table 3). The impact of the stoichiometric ratio between substrates 9a and diphenyl phosphonate (10) was investigated (entries 1−4). At room temperature, increasing the amount of 9a to 2.0 equiv resulted in an improvement to the yield (entries 2 and 3).…”

“…The reaction of nitro derivative 9d, incorporating a powerful electron-withdrawing group at the para position, resulted in the generation of the addition product 11d in only a moderate yield, but an excellent enantioselectivity was retained. Enones 9e−h with chloro, bromo, and fluoro halogen groups, respectively, also reacted smoothly with diphenyl phosphonate (10), providing the adducts 11e−h in good to high yields with excellent ee's. The reaction of (E)-1-phenylpent-2-en-1-one (9i) with 10 gave the 1,4-addition product 11i in a high yield and enantioselectivity.…”

Mechanism and Origin of Remote Stereocontrol in the Organocatalytic Enantioselective Formal C(sp2)–H Alkylation Using Nitroalkanes as Alkylating Agents

“…These transformations do not lead to the creation of any stereocenter at the reaction site but allow for the generation of stereocenter(s) remote from the reaction sitea phenomenon often termed as remote stereocontrol . While the initial findings have already led to the development of other transformations , and applied to the enantioselective synthesis of complex targets, a detailed mechanistic study of this reaction holds the potential to unearth valuable information.…”