Cu- and Ni-catalyzed decarboxylative borylation reactions

A method of preparing the Boc-protected boronic pinacolato ester compound of formula

• comprising treating the compound
• in an aprotic solvent, with bis (pinacolato) diboron (B2pin2), in the presence of at least 20 mole % of a Mg(II) salt and of at least one molar equivalent a lithium compound comprising a (C1-C4) alkyllithium, a (C1-C4) alkoxylithium, or lithium hydroxide, and at least 10 mole % of a Cu or Ni salt;
• in the presence of a 1,3-dicarbonyl ligand forming with the Cu a compound of formula (M)
• wherein R1A and R2A are each independently selected from the group consisting of (C1-C4) alkyl, trifluoromethyl, or phenyl;
• or in the presence of a ligand of formula (L) comprising a bipyridyl of formula
• wherein R1 and R2 are each independently selected from the group consisting of ed (C1-C4) alkyl or (C1-C4) alkoxy, n1 and n2 are each independently 0, 1, or 2, or of a 1,10-phenanthroline of formula
• wherein R3 and R4 are each independently selected from the group consisting of (C1-C4) alkyl, (C1-C4) alkoxy, and phenyl;
• to provide the Boc-protected boronic pinacolato ester compound
• and further comprising cleaving the Boc group of the Boc-protected boronic pinacolato ester compound with trifluoroacetic acid, followed by condensation of the resulting free amino group with compound of formula
• followed by cleavage of pinacolato boronate ester group with phenylboronic acid in aqueous HCl to provide the boronic acid mCBK320 elastase inhibitor compound of formula

A method of preparing the Boc-protected boronic pinacolato ester compound of formula

• comprising treating the compound
• in an aprotic solvent, with bis (pinacolato) diboron (B2pin2), in the presence of at least 20 mole % of a Mg(II) salt and of at least one molar equivalent a lithium compound comprising a (C1-C4) alkyllithium, a (C1-C4) alkoxylithium, or lithium hydroxide, and at least 10 mole % of a Cu or Ni salt;
• in the presence of a 1,3-dicarbonyl ligand forming with the Cu a compound of formula (M)
• wherein R1A and R2A are each independently selected from the group consisting of (C1-C4) alkyl, trifluoromethyl, or phenyl;
• or in the presence of a ligand of formula (L) comprising a bipyridyl of formula -----
• wherein R1 and R2 are each independently selected from the group consisting of (C1-C4) alkyl or (C1-C4) alkoxy, n1 and n2 are each independently 0, 1, or 2, or of a 1,10-phenanthroline of formula
• wherein R3 and R4 are each independently selected from the group consisting of (C1-C4) alkyl, (C1-C4) alkoxy, and phenyl;
• to provide the Boc-protected boronic pinacolato ester compound
• and further comprising cleaving the Boc group and the boronate ester of the Boc-protected boronic pinacolato ester compound with trifluoroacetic acid, followed by condensation of the resulting free amino group with compound of formula
• followed by cleavage of the t-Bu ester, to provide a boronic acid mCBK323 elastase inhibitor compound of formula