Directed openings of 2,3-epoxy alcohols via reactions with isocyanates: synthesis of (+)-erythro-dihydrosphingosine

Abstract

Two methods for the synthesis of 2-(IV-alkylamino) 1,3-diols from 2,3-epoxy alcohols are described. In one procedure (method A) an epoxyurethane (5, 8,11, 14, 16) prepared from the corresponding epoxy alcohol by standard procedures is cyclized to a 2-oxazolidinone derivative (6, 9, 12, 15, 17) in 81-90% yield by treatment with NaH in THF or NaOMe in MeOH. The second procedure (method B) involves treatment of the epoxy alcohol (4, 7,10,13,24) with benzyl isocyanate, an NH3 synthetic equivalent, and NaH in THF at reflux. Hydrolysis of the crude isoxazolidinones by exposure to LiOH in EtOH at reflux smoothly affords 2-(iV-benzylamino) 1,3-diols (22, 23, 30, 31) in 68-72% overall yield. These procedures are highly regioselective; products resulting from intramolecular addition of the urethane nitrogen atom to the epoxide 0-position were not detected. This methodology was applied to a short, highly stereoselective synthesis of (+)-eryfhro-dihydrosphingosine (26) from palmitic aldehyde (47-54% overall yield).

Five-membered oxaza heterocyclic compounds on the basis of epoxides and aziridines

“…Ammazzalorso et al [77] described preliminary structural modification of both initial reactants (epoxide and amine) in the synthesis of compound 29 (Scheme 15). These data are consistent with the results of other studies [72,78,79] on the synthesis of oxazolidin-2-ones 30 via reactions of aryl glycidyl ethers 31 and their analogs (Scheme 16). Epoxide 32 was used as starting compound to obtain potent (+)-L-733 060 neurokinin-1 receptor antagonist [80] (Scheme 17).…”

“…The structure of heterocyclization products depends on the catalyst nature [72] Transformation of epoxy substrate into 1,3-oxazolidin-2-one requires that a group capable of rear intramolecular nucleophilic attack on electrophilic carbon atoms be present in the neighborhood to the oxirane ring. Aryloxiranes were reported to react with tertbutyl alkylcarbamates in the presence of a catalytic amount of potassium tert-butoxide to give 5-aryl-1,3-oxazolidin-2-ones 28 (Ar = Ph, 4-ClC 6 H 4 , 1-naphthyl, R = Bu, Hex, All, Bzl) [76] (Scheme 14).…”

Stereocontrolled Synthesis of Highly Functionalized Quaternary Carbon Centers: A Route to α‐Substituted Serines

“…[8] We reasoned that its hydroboration at the less hindered face of the terminal double bond would generate an unsymmetrical Z allylborane, which could be stereoselectively added to an aldehyde to generate the amino diols 6 that are protected at the quaternary center. [11] One-dimensional nuclear Overhauser enhancement experiments on 7 a enabled us to determine its relative configuration, which is shown in Scheme 3. [9,10] Interestingly, in the presence of a catalytic amount of DBU in CH 2 Cl 2 at room temperature, 6 a exhibited an equilibrium largely shifted towards its regioisomer 7 a, which was readily isolated in 85 % yield after column chromatography.…”

Chiral porphyrin imine manganese complex as catalyst for asymmetric epoxidation of styrene derivatives

“…1,2 Some of the synthetic utility of chiral epoxides are as follows; conversion of chiral epoxides into hydroxy compounds through ring opening reactions, 3 carbon-carbon bond formation and formylation, 4 ringopening reactions of chiral epoxides with isocyanates to yield chiral amino alcohols, 5 Payne rearrangement of converting chiral epoxy alcohols to chiral diols, 6 meso epoxide ring opening with dithiols to form chiral disulfides, 7 rearrangement of chiral epoxides, 8 utilization of terminal epoxides in the synthesis of γ-lactones, 9 in the synthesis of 2,5-disubstituted piperdine alkaloids, 10 and in the synthesis of norlignan currculigine, which is an in vivo anti-arrhythmic active compound. 1,2 Some of the synthetic utility of chiral epoxides are as follows; conversion of chiral epoxides into hydroxy compounds through ring opening reactions, 3 carbon-carbon bond formation and formylation, 4 ringopening reactions of chiral epoxides with isocyanates to yield chiral amino alcohols, 5 Payne rearrangement of converting chiral epoxy alcohols to chiral diols, 6 meso epoxide ring opening with dithiols to form chiral disulfides, 7 rearrangement of chiral epoxides, 8 utilization of terminal epoxides in the synthesis of γ-lactones, 9 in the synthesis of 2,5-disubstituted piperdine alkaloids, 10 and in the synthesis of norlignan currculigine, which is an in vivo anti-arrhythmic active compound.…”