Allylation Reactions of Aldehydes with Allylboronates in Aqueous Media: Unique Reactivity and Selectivity that are Only Observed in the Presence of Water

Abstract

Zn(OH)2-catalyzed allylation reactions of aldehydes with allylboronates in aqueous media have been developed. In contrast to conventional allylboration reactions of aldehydes in organic solvents, the α-addition products were obtained exclusively. A catalytic cycle in which the allylzinc species was generated through a B-to-Zn exchange process is proposed and kinetic studies were performed. The key intermediate, an allylzinc species, was detected by HRMS (ESI) analysis and by online continuous MS (ESI) analysis. This analysis revealed that, in aqueous media, the allylzinc species competitively reacted with the aldehydes and water. An investigation of the reactivity and selectivity of the allylzinc species by using several typical allylboronates (6a-6d) clarified several important roles of water in this allylation reaction. The allylation reactions of aldehydes with allylboronic acid 2,2-dimethyl-1,3-propanediol esters proceeded smoothly in the presence of catalytic amounts of Zn(OH)2 and achiral ligand 4d in aqueous media to afford the corresponding syn-adducts in high yields with high diastereoselectivities. In all cases, the α-addition products were obtained and a wide substrate scope was tolerated. Furthermore, this reaction was applied to asymmetric catalysis by using chiral ligand 9. Based on the X-ray structure of the Zn-9 complex, several nonsymmetrical chiral ligands were also found to be effective. This reaction was further applied to catalytic asymmetric alkylallylation, chloroallylation, and alkoxyallylation processes and the synthetic utility of these reactions has been demonstrated.

Zinc Hydroxide‐Catalyzed Asymmetric Allylation of Acetophenones with Amido‐Functionalized Allylboronate in Water

“…Facial selectivity is briefly discussed with reaction modes A – C , in which cyclic structure consisting of a substrate and an allylic species would be formed (Figure ) . The interaction between the catalyst's didecylamino moiety and the amide hydrogen of 1 may be responsible for the high reaction efficiency and enantiocontrol because of the fact that the amide hydrogen atom on 1 was essential to the success of the reaction . Modes B and C would be destabilized due to the steric repulsion between the catalyst's aryl group and the substrate phenyl group (mode B ) or the catalyst's side chain (mode C ).…”

“…Besides indium species, allylboronates can be used for catalytic enantioselective allylation in aqueous media. Kobayashi and his co‐workers realized the relevant reaction of aldehydes by employing chiral zinc catalysis in water‐acetonitrile solution (Scheme b) . They also succeeded the development of an analogous reaction using imino substrates, where chiral allylglycine derivatives were provided with up to 88% ee .…”

Biocatalytic Production of Aldehydes: Exploring the Potential of Lathyrus cicera Amine Oxidase

“…We, therefore, decided to test the enzymatic activity of LCAO against a larger number of substrates to obtain a variety of aldehydes that may be used as intermediates for the synthesis of molecules with potentially interesting pharmacological profiles. Since this biocatalytic process occurs in aqueous media, aldehydes can be actually used in domino processes by adding other enzymes that use them as substrates [19,40,41] or in other organic transformations that can be carried out directly in water [42][43][44]. In this study, we tested the activity of LCAO toward different classes of commercially available primary amines: 14 substituted β-ethylamines, three substituted γ-propylamines and three linear amines (Table 2 and Figure S6).…”

Synthesis of a Bolm's 2,2′‐Bipyridine Ligand Analogue and Its Applications

“…[8] The synthetic approach was slightly modified by , who prepared (S,S)-1. [9] Bolm's ligand 1 proved to be a useful chiral ligand in various types of metal-catalyzed asymmetric reactions as e. g. allylation of aldehydes, [10] opening of epoxides, [11,12,13] Michael addition, [14] Mukaiyama-aldol reaction, [15] hydroxymethylation, [16] CÀH activation of indols, [17] and most recently Diels-Alder reaction. [18] In addition, its complexes with non-toxic metal salts (e. g. Fe, Bi, Sc) also showed interesting behavior in the aqueous media making it an important player in the field of green chemistry.…”