Convergent Synthesis of 1α-Hydroxyvitamin D5

Abstract

An eleven-step, high-yielding (46%) synthesis of 1α-hydroxyvitamin D 5 (2) starting from vitamin D 2 (4) is described, in

First Organocatalyzed Asymmetric Michael Addition of Aldehydes to Vinyl Sulfones

“…Optical rotation measured [α] 25 D = −6.79 ( c = 0.118, CHCl 3 ) compared to literature data, [α] 20 D = −9.47 ( c = 2.126, CHCl 3 ).…”

First Organocatalyzed Asymmetric Michael Addition of Aldehydes to Vinyl Sulfones

“…Optical rotation measured [α] 25 D = −6.79 ( c = 0.118, CHCl 3 ) compared to literature data, [α] 20 D = −9.47 ( c = 2.126, CHCl 3 ).…”

Enantioselective Synthesis of the Aggregation Pheromone of Odontothrips loti (Haliday) and Its Stereoisomers

“…[ 22 ] According to Evans’ procedure, [ 23 ] the new stereocenter of the alkylated oxazolidinone imide was confirmed as R . The chiral auxiliary was removed by the reductive cleavage with LiAlH 4 [ 24 ] and afforded ( R )‐5‐methyl‐2‐(prop‐1‐en‐2‐yl)hex‐4‐en‐1‐ol (( R )‐ 11 ) (73% yield, 81% ee, determined by chiral HPLC of its MBT derivative, [ 25,26 ] see details in Supporting Information). Its specific rotation was in accord with the reference data, [ 27 ] which also supported that the new chiral carbon of alkylated oxazolidinone imide ( R , R )‐ 10 had R configuration.…”

“…[21] Chiral isopentenyl was then introduced via diastereoselective alkylation of oxazolidinone imide (R)-8 with 3,3-dimethylallylbromide (9) and gave (R)-3-((R)-5-methyl-2-(prop-1-en-2-yl)hex-4-enoyl)-4phenyloxazolidin-2-one ((R,R)-10) (60% yield, dr 91:9, determined by 13 C NMR spectra). [22] According to Evans' procedure, [23] the new stereocenter of the alkylated oxazolidinone imide was confirmed as R. The chiral auxiliary was removed by the reductive cleavage with LiAlH 4 [24] and afforded (R)-5-methyl-2-(prop-1-en-2-yl)hex-4-en-1-ol ((R)-11) (73% yield, 81% ee, determined by chiral HPLC of its MBT derivative, [25,26] see details in Supporting Information). Its specific rotation was in accord with the reference data, [27] which also supported that the new chiral carbon of alkylated oxazolidinone imide (R,R)-10 had R configuration.…”

Synthesis of 1α-Hydroxyvitamin D5 Using a Modified Two Wavelength Photolysis for Vitamin D Formation

“…A convergent approach to the synthesis of 1α-hydroxyvitamin D 5 has been recently reported . The convergent synthetic approach was described as an 11-step total synthesis of 1α-hydroxyvitamin D 5 in high overall yield (46%) from commercially available vitamin D 2 .…”

First Organocatalyzed Asymmetric Michael Addition of Aldehydes to Vinyl Sulfones

“…Optical rotation measured [α] 25 D = −6.79 ( c = 0.118, CHCl 3 ) compared to literature data, [α] 20 D = −9.47 ( c = 2.126, CHCl 3 ).…”

Enantioselective Synthesis of the Aggregation Pheromone of Odontothrips loti (Haliday) and Its Stereoisomers

“…[ 22 ] According to Evans’ procedure, [ 23 ] the new stereocenter of the alkylated oxazolidinone imide was confirmed as R . The chiral auxiliary was removed by the reductive cleavage with LiAlH 4 [ 24 ] and afforded ( R )‐5‐methyl‐2‐(prop‐1‐en‐2‐yl)hex‐4‐en‐1‐ol (( R )‐ 11 ) (73% yield, 81% ee, determined by chiral HPLC of its MBT derivative, [ 25,26 ] see details in Supporting Information). Its specific rotation was in accord with the reference data, [ 27 ] which also supported that the new chiral carbon of alkylated oxazolidinone imide ( R , R )‐ 10 had R configuration.…”

“…[21] Chiral isopentenyl was then introduced via diastereoselective alkylation of oxazolidinone imide (R)-8 with 3,3-dimethylallylbromide (9) and gave (R)-3-((R)-5-methyl-2-(prop-1-en-2-yl)hex-4-enoyl)-4phenyloxazolidin-2-one ((R,R)-10) (60% yield, dr 91:9, determined by 13 C NMR spectra). [22] According to Evans' procedure, [23] the new stereocenter of the alkylated oxazolidinone imide was confirmed as R. The chiral auxiliary was removed by the reductive cleavage with LiAlH 4 [24] and afforded (R)-5-methyl-2-(prop-1-en-2-yl)hex-4-en-1-ol ((R)-11) (73% yield, 81% ee, determined by chiral HPLC of its MBT derivative, [25,26] see details in Supporting Information). Its specific rotation was in accord with the reference data, [27] which also supported that the new chiral carbon of alkylated oxazolidinone imide (R,R)-10 had R configuration.…”

Synthesis of 1α-Hydroxyvitamin D5 Using a Modified Two Wavelength Photolysis for Vitamin D Formation

“…A convergent approach to the synthesis of 1α-hydroxyvitamin D 5 has been recently reported . The convergent synthetic approach was described as an 11-step total synthesis of 1α-hydroxyvitamin D 5 in high overall yield (46%) from commercially available vitamin D 2 .…”

First Organocatalyzed Asymmetric Michael Addition of Aldehydes to Vinyl Sulfones

“…Optical rotation measured [α] 25 D = −6.79 ( c = 0.118, CHCl 3 ) compared to literature data, [α] 20 D = −9.47 ( c = 2.126, CHCl 3 ).…”

Enantioselective Synthesis of the Aggregation Pheromone of Odontothrips loti (Haliday) and Its Stereoisomers

“…[ 22 ] According to Evans’ procedure, [ 23 ] the new stereocenter of the alkylated oxazolidinone imide was confirmed as R . The chiral auxiliary was removed by the reductive cleavage with LiAlH 4 [ 24 ] and afforded ( R )‐5‐methyl‐2‐(prop‐1‐en‐2‐yl)hex‐4‐en‐1‐ol (( R )‐ 11 ) (73% yield, 81% ee, determined by chiral HPLC of its MBT derivative, [ 25,26 ] see details in Supporting Information). Its specific rotation was in accord with the reference data, [ 27 ] which also supported that the new chiral carbon of alkylated oxazolidinone imide ( R , R )‐ 10 had R configuration.…”

“…[21] Chiral isopentenyl was then introduced via diastereoselective alkylation of oxazolidinone imide (R)-8 with 3,3-dimethylallylbromide (9) and gave (R)-3-((R)-5-methyl-2-(prop-1-en-2-yl)hex-4-enoyl)-4phenyloxazolidin-2-one ((R,R)-10) (60% yield, dr 91:9, determined by 13 C NMR spectra). [22] According to Evans' procedure, [23] the new stereocenter of the alkylated oxazolidinone imide was confirmed as R. The chiral auxiliary was removed by the reductive cleavage with LiAlH 4 [24] and afforded (R)-5-methyl-2-(prop-1-en-2-yl)hex-4-en-1-ol ((R)-11) (73% yield, 81% ee, determined by chiral HPLC of its MBT derivative, [25,26] see details in Supporting Information). Its specific rotation was in accord with the reference data, [27] which also supported that the new chiral carbon of alkylated oxazolidinone imide (R,R)-10 had R configuration.…”

Synthesis of 1α-Hydroxyvitamin D5 Using a Modified Two Wavelength Photolysis for Vitamin D Formation

“…A convergent approach to the synthesis of 1α-hydroxyvitamin D 5 has been recently reported . The convergent synthetic approach was described as an 11-step total synthesis of 1α-hydroxyvitamin D 5 in high overall yield (46%) from commercially available vitamin D 2 .…”