Pyrrolidine and oxazolidine ring transformations in proline and serine derivatives of α-hydroxyphosphonates induced by deoxyfluorinating reagents

Abstract

Transformations of a-hydroxyphosphonates derived from proline or serine by treatment with different deoxyfluorinating reagents (DAST, Deoxofluor, PyFluor) are reported. Depending on the applied reagent, as well as the protecting group used (N-Cbz, N-Boc, N-Bn) different types of products are observed. The reaction of N-Cbz or N-Boc prolinols with DAST or Deoxofluor due to aziridinium intermediate participation gave fluorinated amino phosphonates such as piperidine and pyrrolidine derivatives and/or oxazolidine-2-ones. Similarly, the analogous reaction of N-Cbz or N-Boc protected serinol yielded oxazolidine-2-ones or its fluorinated analogues. As the second type of product formed by DASTinduced reaction of serine derivatives, aziridines were obtained. Only in the case of deoxyfluorination of N-benzyl prolinols were both diastereoisomers of b-fluoropiperidine-a-phosphonates formed, while the reaction of protected N-benzyl serinols gave fluorinated oxazolidines. Moreover, application of PyFluor gave sulfonate derivatives.

Highly Diastereoselective Construction of Carbon– Heteroatom Quaternary Stereogenic Centers in the Synthesis of Analogs of Bioactive Compounds: From Monofluorinated Epoxyalkylphosphonates to α-Fluoro-, β-, or γ-Amino Alcohol Derivatives of Alkylphosphonates

“…Moreover, the formation of compound 27 supports the proposed mechanism. We already observed the participation of the neighboring group (substituted amines) during deoxyfluorination of α-hydroxy-β-aminophosphonate derivatives of amino acids, leading to β-fluoro-α - aminophosphonates (Kazmierczak and Koroniak, 2012 ; Kaczmarek et al, 2018 ).…”

“…derivatives of amino acids, leading to β-fluoro-αaminophosphonates (Kazmierczak and Koroniak, 2012;Kaczmarek et al, 2018).…”

Diethylaminosulfur Trifluoride (DAST) Mediated Transformations Leading to Valuable Building Blocks and Bioactive Compounds

“…The ring expansion product was obtained as expected (Scheme 9). [33] However, application of a similar synthetic strategy, which started from substrates protected with N-Cbz (R = Bn) 36 a and N-Boc (R = tBu) 36 b groups, resulted in a mixture of products (Scheme 10). Obviously, one of these 38 a,b was a derivative coming from the ring expansion by the aziridinium ion formed (route a).…”

“…Deoxyfluorination of 34. [33] neighboring group of the carbamate oxygen on the activated carbon atom (route b). [33] On the other hand, fluorination of N-trityl (Tr) or N-pmethoxybenzyl (PMB) prolinols 40 yielded the expected major products 41 resulting from ring expansion (Scheme 11).…”

“…[33] neighboring group of the carbamate oxygen on the activated carbon atom (route b). [33] On the other hand, fluorination of N-trityl (Tr) or N-pmethoxybenzyl (PMB) prolinols 40 yielded the expected major products 41 resulting from ring expansion (Scheme 11). Importantly, as demonstrated by Cossy, an additional N-Boc protected amino group in the structure of substrates is fully tolerated in the reaction.…”