In our ongoing research of previously synthesized and investigated α-Amino acids derived diazoketones (AADDK) in the MedChem relevant building blocks synthesis, we are reporting their behavior in TM-catalyzed intramolecular cyclizations. We found that treatment of Boc-protected ones by the catalytical amount of (5%) Cu(OTf)2 in CH2Cl2 leads to Boc-protecting cleavage by intermediate carbenoid affording the cyclic urethanes type A (Scheme 1). The analogous transformation using Rh2(OAc)4 as a catalyst leads to corresponding azetidinone type B keeping stereochemical issues. In contrast to previous precedents of such reactions, our combination of flow techniques and “slow addition protocols” allow us to minimize the dimerization of carbenoid intermediate and achieve the preparative scale of the reactions around 100 g from 1 synthetic run. Inspired by the results, we tested in transformation the corresponding β-amino acids derived diazoketones obtained according to our standard sequence photo-Wolf homologation – acid activation – CH2N2 treatment. By analogy with α-amino acids derived, these substrates give the corresponding pyrrolidones C in high preparative yields and preserve stereochemistry.<br/>In this report, we will show the scope of the reaction and discuss the structural factors' impact on the reaction behavior.

Amino acids derived diazoketones (AADDK) in the synthesis of MedChem relevant building blocks via TM-catalyzed reactions

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