Synthesis of All Diastereomers of the 2-Deoxypentoses and the 2,6-Dideoxyhexoses from 2-Phenyl-1,3-dioxan-5-one Hydrate

Abstract

All diastereomers of the 2‐deoxypentoses and the 2,6‐dideoxyhexoses were synthesized from 2‐phenyl‐1,3‐dioxan‐5‐one hydrate (1), by alkylation via the RAMP‐hydrazone (2). Some of the diastereomers were synthesized in the racemic form via the dimethylhydrazone (28). The 2‐deoxypentoses were synthesized by alkylation with allyl bromide, followed by stereoselective reduction, ozonolysis, and deprotection. The 2,6‐dideoxypentoses were synthesized by dialkylation with allyl bromide and methyl iodide.

Synthesis of Luffarin L and 16-epi-Luffarin L Using a Temporary Silicon-Tethered Ring-Closing Metathesis Reaction

“…This compound was deprotected with PPTS to give triol 13 that by treatment with benzaldehyde dimethyl acetal in the presence of camphorsulfonic acid gave 14 . Oxidation of 14 with Dess–Martin periodinane − led to ketone 15 that without isolation was transformed by Wittig reaction into compound 16 Z . The olefination reaction was optimized under diverse conditions using several reactants, bases, and temperatures to obtain the desired regioisomer 16 Z .…”

Synthesis of Luffarin L and 16-epi-Luffarin L Using a Temporary Silicon-Tethered Ring-Closing Metathesis Reaction

“…This compound was deprotected with PPTS to give triol 13 that by treatment with benzaldehyde dimethyl acetal in the presence of camphorsulfonic acid gave 14 . Oxidation of 14 with Dess–Martin periodinane − led to ketone 15 that without isolation was transformed by Wittig reaction into compound 16 Z . The olefination reaction was optimized under diverse conditions using several reactants, bases, and temperatures to obtain the desired regioisomer 16 Z .…”

N , N -Dialkylhydrazones in Organic Synthesis. From Simple N , N -Dimethylhydrazones to Supported Chiral Auxiliaries

“…143 All stereoisomers of the 2-deoxypentoses and the 2,6-dideoxyhexoses can be synthesized from 2-phenyl-1,3-dioxan-5-one RAMP-hydrazone by R-alkylation with allyl bromide or R,R′-bisalkylation with allyl bromide and methyl iodide, respectively (Scheme 16). 144 Interestingly, the RAMPhydrazone of the C s -symmetric ketone formed one diastereomer, 109, on equilibration by prolonged storage. The diastereomer 109 was monoalkylated, giving the product with the new R-alkyl group in the equatorial position with high selectivity.…”

“…The second alkylation introduced the α′-alkyl group in the axial position, giving 110 (R 3 = Me, allyl; R 4 = allyl, Me). Aqueous ammonium dihydrogen phosphate hydrolysis of the hydrazone, followed by stereoselective carbonyl reduction, and ozonolysis of the allyl CC, gave benzylidene-protected aldose or furanose 114 . The deoxysugar diastereomers 114 were synthesized in the racemic form via the corresponding N , N -dimethylhydrazones.…”

Synthesis of 2,6-Dideoxysugars via Ring-Closing Olefinic Metathesis

“…Because of the high density of stereogenic centers in these compounds, their synthesis from nonchiral compounds represents a challenge for synthetic chemists. All diastereomers of the 2,6-dideoxypyranoses have been previously synthesized and are all found in nature in medicinally interesting glycosides . Our strategy for the synthesis of 2,6-dideoxypyranosides was to utilize the RCM reaction for the formation of β,γ-unsaturated δ-lactones.…”

Synthesis of Luffarin L and 16-epi-Luffarin L Using a Temporary Silicon-Tethered Ring-Closing Metathesis Reaction

“…This compound was deprotected with PPTS to give triol 13 that by treatment with benzaldehyde dimethyl acetal in the presence of camphorsulfonic acid gave 14 . Oxidation of 14 with Dess–Martin periodinane − led to ketone 15 that without isolation was transformed by Wittig reaction into compound 16 Z . The olefination reaction was optimized under diverse conditions using several reactants, bases, and temperatures to obtain the desired regioisomer 16 Z .…”

N , N -Dialkylhydrazones in Organic Synthesis. From Simple N , N -Dimethylhydrazones to Supported Chiral Auxiliaries

“…143 All stereoisomers of the 2-deoxypentoses and the 2,6-dideoxyhexoses can be synthesized from 2-phenyl-1,3-dioxan-5-one RAMP-hydrazone by R-alkylation with allyl bromide or R,R′-bisalkylation with allyl bromide and methyl iodide, respectively (Scheme 16). 144 Interestingly, the RAMPhydrazone of the C s -symmetric ketone formed one diastereomer, 109, on equilibration by prolonged storage. The diastereomer 109 was monoalkylated, giving the product with the new R-alkyl group in the equatorial position with high selectivity.…”

“…The second alkylation introduced the α′-alkyl group in the axial position, giving 110 (R 3 = Me, allyl; R 4 = allyl, Me). Aqueous ammonium dihydrogen phosphate hydrolysis of the hydrazone, followed by stereoselective carbonyl reduction, and ozonolysis of the allyl CC, gave benzylidene-protected aldose or furanose 114 . The deoxysugar diastereomers 114 were synthesized in the racemic form via the corresponding N , N -dimethylhydrazones.…”

Synthesis of 2,6-Dideoxysugars via Ring-Closing Olefinic Metathesis

“…Because of the high density of stereogenic centers in these compounds, their synthesis from nonchiral compounds represents a challenge for synthetic chemists. All diastereomers of the 2,6-dideoxypyranoses have been previously synthesized and are all found in nature in medicinally interesting glycosides . Our strategy for the synthesis of 2,6-dideoxypyranosides was to utilize the RCM reaction for the formation of β,γ-unsaturated δ-lactones.…”

Synthesis of Luffarin L and 16-epi-Luffarin L Using a Temporary Silicon-Tethered Ring-Closing Metathesis Reaction

“…This compound was deprotected with PPTS to give triol 13 that by treatment with benzaldehyde dimethyl acetal in the presence of camphorsulfonic acid gave 14 . Oxidation of 14 with Dess–Martin periodinane − led to ketone 15 that without isolation was transformed by Wittig reaction into compound 16 Z . The olefination reaction was optimized under diverse conditions using several reactants, bases, and temperatures to obtain the desired regioisomer 16 Z .…”

N , N -Dialkylhydrazones in Organic Synthesis. From Simple N , N -Dimethylhydrazones to Supported Chiral Auxiliaries

“…143 All stereoisomers of the 2-deoxypentoses and the 2,6-dideoxyhexoses can be synthesized from 2-phenyl-1,3-dioxan-5-one RAMP-hydrazone by R-alkylation with allyl bromide or R,R′-bisalkylation with allyl bromide and methyl iodide, respectively (Scheme 16). 144 Interestingly, the RAMPhydrazone of the C s -symmetric ketone formed one diastereomer, 109, on equilibration by prolonged storage. The diastereomer 109 was monoalkylated, giving the product with the new R-alkyl group in the equatorial position with high selectivity.…”

“…The second alkylation introduced the α′-alkyl group in the axial position, giving 110 (R 3 = Me, allyl; R 4 = allyl, Me). Aqueous ammonium dihydrogen phosphate hydrolysis of the hydrazone, followed by stereoselective carbonyl reduction, and ozonolysis of the allyl CC, gave benzylidene-protected aldose or furanose 114 . The deoxysugar diastereomers 114 were synthesized in the racemic form via the corresponding N , N -dimethylhydrazones.…”

Synthesis of 2,6-Dideoxysugars via Ring-Closing Olefinic Metathesis

“…Because of the high density of stereogenic centers in these compounds, their synthesis from nonchiral compounds represents a challenge for synthetic chemists. All diastereomers of the 2,6-dideoxypyranoses have been previously synthesized and are all found in nature in medicinally interesting glycosides . Our strategy for the synthesis of 2,6-dideoxypyranosides was to utilize the RCM reaction for the formation of β,γ-unsaturated δ-lactones.…”