Catalytic One‐Pot Oxetane to Carbamate Conversions: Formal Synthesis of Drug Relevant Molecules

Abstract

Oxetanes are versatile building blocks in drug-related synthesist oi nduce property-modulating effects.W hereas related oxiranes are widely used in coupling chemistry with carbon dioxide (CO 2 )t o affordv alue-added commodity chemicals,o xetane/ CO 2 couplings remaine xtremelyl imited despite the recent advances in the synthesis of these four-membered heterocycles.H ere we report an effective onepot three-componentr eaction( 3CR) strategy for the coupling of (substituted) oxetanes,a minesa nd CO 2 to affordavariety of functionalized carbamates with excellent chemoselectivity andg ood yields.T he process is mediated by an aluminium-based catalyst under relatively mild conditions and the developed catalytic methodology can be applied to the formal synthesiso ft wo pharmaceutically relevant carbamates with the 3CR being akey step.

Catalytic Transformations of Functionalized Cyclic Organic Carbonates

“…The stereodivergent synthesis leading to these carbamates was supported by various control experiments, and conceptually this approach offers a new tool for the stereodivergent synthesis of CO 2 ‐derived fine chemicals albeit with moderately high yields and sometimes relatively long reaction times (66 h) were required. At a later stage, aminolysis of in situ prepared six‐membered carbonates obtained from oxetanes and CO 2 demonstrated that this chemistry is of use for the preparation of drug‐relevant molecules such as the muscle relaxant Carisoprodol . The Lu laboratory reported a similar concept for chiral carbamate synthesis from meso ‐epoxides using an enantiopure dinuclear Co III catalyst …”

Novel high reactive bifunctional five- and six-membered bicyclic dicarbonate – synthesis and characterisation

“…[8][9][10][11][12][13][14][15] Six-membered cyclic carbonates are obtained by the reaction of oxetanes with CO 2 . 16,17 Bi-or trifunctional monomers based on carbonates may be used to create multifunctional materials for advanced purposes, for example, in medical science for drug delivery. [18][19][20] Bifunctional bicyclic dicarbonate bearing ve-membered and six-membered carbonate rings have already been presented in the literature.…”

Effect of an Al(III) Complex on the Regio- and Stereoisomeric Formation of Bicyclic Organic Carbonates

“…The lower potential of chloride-based nucleophiles in epoxide/CO2 coupling reactions follows general trends typically noted in this area. 56 The selectivity was neither perturbed by the CO2 pressure (Table 1, entries [19][20][21][22], and was only affected slightly by the choice of solvent (entries [14][15][16][17][18]. In these cases, a lower selectivity goes accompanied by a lower conversion, and therefore MEK was selected as the solvent for further studies.…”

“…Contemporary research focusing on the use of carbon dioxide as a readily available carbon feedstock in organic synthesis 18 has a major focus on the discovery of new transformations 9-14 while improving existing ones. [15][16][17][18][19] Whereas the vast majority of the conversions that utilize CO2 as one of the substrates involve catalytic protocols that afford the final product in racemic form, recent work has shown an upsurge of more challenging, enantioselective or stereo-divergent transformations. [20][21][22][23][24][25] Among the most common synthetic efforts, the ones that incorporate CO2 whilst preserving a high oxidation state of the carbon center originally present in the C1 reagent prevail.…”