The stereoselective synthesis of oxetanes; exploration of a new, Mitsunobu-style procedure for the cyclisation of 1,3-diols

Abstract

A solution of 2-methyl-3-[1-(phenylsulfanyl)cyclohexyl]propane-1,3-diol 1 in toluene treated with triphenylphosphine, Ziram® 2 and DEAD, gave 3-methyl-2-[1-(phenylsulfanyl)cyclohexyl]oxetane 3 in 85% yield. A mechanistic study has been undertaken, optimal conditions have been found and the range of substrates for which the reaction is useful has been explored. We include the results of an X-ray study which shows that compound 33 (the oxidation product of diol 1) is a sulfone rather than a sulfoxide as previously reported. Scheme 2 Scheme 3

Recent Advances in the Mitsunobu Reaction: Modified Reagents and the Quest for Chromatography‐Free Separation

“…The products available via the Mitsunobu reaction have been expanded or the procedure has been improved to include styrene oxides with a high level of stereoretention, [32] oxetanes, [29] lactones from hindered chiral alcohols with retention of configuration, [73] aldehydes from 1,1-disubstituted-1,2-diols, [85] carbamate esters, [57,86,87] γ-lactams from amino alcohols, [88] primary amines, [89] tertiary benzylamines, [40] alkylated hydrazines, [90] nitriles, [41,61] isocyanates, [31] thiocyanates, [91] hydroxyalkyl azides, [69,92] and cisor trans-1,2-diazides from epoxides or trans-diols. [93] Hydra- zine derivatives can be obtained directly from the azodicarboxylate and an alcohol, [94] vinylhydrazinecarboxylates from ketones in the presence of dimethyl azodicarboxylate, [95] and hydrazylmethyl uracil derivatives from N 3 -benzyluracil, TMAD, and N-hydroxymethylphthalimide.…”

8 Heterocyclic chemistry

“…Warren has reported a synthesis of oxetanes from 1,3-diols using a modification of the Mitsunobu conditions for ether synthesis, as shown in Scheme 11. 22 The zinc salt Ziram® was found uniquely to promote cyclisation in the presence of DEAD and triphenylphosphine. The scope of the reaction was found to be general.…”

From (Phenylsulfanyl)cycloalkanecarbaldehydes to Optically Active Spirocyclic Tetrahydrofurans: Stereospecific Resolution of Symmetric Aldehydes through (S)‐Proline‐Catalysed Aldol Reaction

“…Recently, we developed an enantioselective approach to spirocyclic alkyltetrahydrofurans 22. This achievement was based on the conversion of strained carbocyclic aldehydes into enantiomerically enriched cycloalkyl phenylsulfanyl diol adducts, which were subsequently converted into spirocyclic compounds by acid‐catalysed phenylsulfanyl migration 23…”