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. 2018 Jul 6;8(43):24444-24457.
doi: 10.1039/c8ra05186k. eCollection 2018 Jul 2.

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

Patrycja Kaczmarek  1 , Magdalena Rapp  1 , Henryk Koroniak  1
Affiliations

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

Patrycja Kaczmarek et al. RSC Adv. .

Abstract

Transformations of α-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 DAST-induced reaction of serine derivatives, aziridines were obtained. Only in the case of deoxyfluorination of N-benzyl prolinols were both diastereoisomers of β-fluoropiperidine-α-phosphonates formed, while the reaction of protected N-benzyl serinols gave fluorinated oxazolidines. Moreover, application of PyFluor gave sulfonate derivatives.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1. Deoxyfluorination of prolinol with DAST.
Scheme 2
Scheme 2. Structures of starting α-hydroxyphosphonates proline derivatives 1–3a,b.
Scheme 3
Scheme 3. Reaction of 1–2a,b with DAST (Table 1) (4 43% and 6a,b 45%; 5 38% and 7a,b 53%); or DeoxoFluor (CH2Cl2, RT, 24 h)(4 38% and 6a,b 43%; 5 30% and 7a,b 48%); and deprotection of 5 (8 73%); [configurations of stereogenic centres in the text].
Scheme 4
Scheme 4. The slightly twisted boat conformation of 4 with observed correlations and values of coupling constants.
Scheme 5
Scheme 5. Reaction of 1–2a,b with PyFluor (PyFluor, DBU, MePh, RT, 5d; 11a,b 78%, 12a,b 74%).
Scheme 6
Scheme 6. The conformations of 13a and 13b with observed 19F–1H NOEs correlations and some values of coupling constants.
Scheme 7
Scheme 7. Reaction of 15–16a with DAST (i) or DeoxoFluor (ii) from 15a: DAST: 17 32% and 18a 17%; from 16a (Table 3), and preparation of 20 ((i) Ac2O, K2CO3, AcOEt, 20 82%).
Scheme 8
Scheme 8. The mechanism of DAST-induced transformation of 16a leading to 21 or 22a.
Scheme 9
Scheme 9. Reaction of 15–16a with PyFluor. (i) PyFluor, DBU, MePh, RT, 5d; 23a 60%, 24a (47%).
Scheme 10
Scheme 10. Reaction of 25a,b with DAST or PyFluor. (i) DAST, RT 0.5 h (26a 58%); (ii) PyFluor, DBU, MePh, RT, 5d; 26a (37%).
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