Ivon Y. Alpha-Heterosubstituted MIDA boronates

This thesis is devoted to the study of α-heterosubstituted MIDA boronates. A key role among them is addressed to acyl MIDA boronates – a novel class of organoboron compounds. Great attention is focused on the investigation of the reactivity of the carbonyl group of acyl MIDA boronates toward nucleophiles, which are typical for aliphatic aldehydes. In addition, the synthesis and study of aliphatic α-borylated α-bromoketones were performed. A method for the synthesis of a trifunctional C2-building block – 1-(trimethylsilyl)-vinyl MIDA boronate has been developed. Orthogonal transformations of the above-mentioned compound were carried out according to all three functional groups. A procedure for the preparation of acyl MIDA boronates based on 1-substituted alkenyl MIDA boronates has been explored. Optimal results were obtained in the case of a two-step sequence: dihydroxylation of an alkene group followed by cleavage of the obtained diol with periodic acid. A method for in situ generation of formyl MIDA boronate – the first homologue of the acyl MIDA boronate class has been developed in this work for the first time. The compound has been synthesized by oxidation of hydroxymethyl MIDA boronate under modified Swern reaction conditions. Formylboronate has been characterized by NMR on 1H and 13C nuclei, and its stability was investigated. The conditions for its reactions with a wide range of nucleophiles were investigated. The study of its reactions with heteroatom nucleophiles has confirmed the hypothesis that the reactivity of its carbonyl group is similar to that of aldehydes. Testing of organometallic C-nucleophiles in the addition reactions to the formyl MIDA boronate has been done The search for reagents with an optimal balance of nucleophilicity and basicity has lead up to the successful addition of allyl- and propargyl-zinc reagents, alkynyl-titanium reagents, and lithium enolates of ketones, esters, and nitriles. Homoallyl and allenic α-hydroxyboronates; propargyl α-hydroxyboronates, and borylated aldols have been obtained by the action of the above reagents on pre-generated formyl MIDA boronate. The obtained propargylic α-hydroxyboronates and aldols were oxidized to the corresponding alkynyl-substituted acylboronates (borylated ynones) and β-dicarbonyl MIDA boronates. The synthesis of the compounds of both types is unprecedented. The possibility of using β-dicarbonyl MIDA boronates as 1,3-dielectrophiles was shown in the examples of cyclization to borylated pyrazoles. A method for preparation of the aliphatic α-borylated α-bromoketones containing functional groups (ethers, esters, carbamate) has been developed starting from β-substituted vinyl MIDA boronates. A key transformation of the synthetic sequence is the bromohydroxylation of alkenylboronates by the action of N-bromosuccinimide in aqueous medium. For most of the tested substrates, the reaction is regiospecific and stereoselective. In general, it occurs with the retention of the C-B bond and it is tolerant to such functional groups as ethers, esters, and the remote carbamate-protected amine. However, the involvement of nucleophilic functional groups has been observed in the bromo-hydroxylation step of alkenyl MIDA boronates, in the cases, where five-membered cycles formation is possible and electrofuges such as benzyl and tert-butyl groups are present. All obtained vicinal bromohydrins have been successfully oxidized to α-borylated α-bromoketones. The possibility of using these compounds as mono- and dielectrophiles has been demonstrated by examples of nucleophilic substitution of the halogen atom and heterocyclization to borylated thiazoles and furan.