(+)-(3S)-3,4-dihydro-3-tert-butyldimethylsiloxymethyl-2-methyl-1(2H)-isoquinolinone | 215928-80-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: (+)-(3S)-3,4-dihydro-3-tert-butyldimethylsiloxymethyl-2-methyl-1(2H)-isoquinolinone
• 英文别名: (3S)-3-[[tert-butyl(dimethyl)silyl]oxymethyl]-2-methyl-3,4-dihydroisoquinolin-1-one
• CAS: 215928-80-6
• 化学式: C₁₇H₂₇NO₂Si
• 分子量: 305.492
• InChiKey: XDIBQBKYVNNYQO-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.71
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (+)-(3S)-3,4-dihydro-3-tert-butyldimethylsiloxymethyl-2-methyl-1(2H)-isoquinolinone 在 间戊二烯 、 氨 、 sodium acetate 、 lithium 、 对甲苯磺酰肼 、 叔丁醇 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 1.25h， 生成 (3S,8aS)-3-[[tert-butyl(dimethyl)silyl]oxymethyl]-2,8a-dimethyl-4,6,7,8-tetrahydro-3H-isoquinolin-1-one
  参考文献：
  名称：

  Preparation and Diastereoselective Birch Reduction−Alkylation of Chiral 3,4-Dihydro-1(2H)-isoquinolinones. Enantiospecific Syntheses and Opioid Receptor Affinities of Several Hydro-2,3- dimethyl-1H-7,12a-methanobenzo[6,7]cycloocta[1,2-c]pyridine-9-ols

  摘要：

  Synthetic procedures have been developed to provide 2,3-disubstituted-3,4-dihydro-1(2H)-isoquinones 6, 10, and 15 from (1R,2S)-ephedrine, (1R,2R)-pseudoephedrine, and L-phenylalanine. Birch reduction of 6 and 10 gave enantiomerically related lactam enolates that were alkylated with methyl iodide, allyl bromide, benzyl bromide, p-benzyloxybenzyl bromide, and p-methoxybenzyl bromide to give 7a-7e, 11a, and 11b with diastereoselectivities > 20:1. Birch reduction-methylation of 15 gave 19 with a diastereoselectivity of >35:1. Selective reduction of the disubstituted double bond in 19 with diimide and cleavage of the tert-butyldimethylsilyl ether gave 20b, from which iodoetherification under thermodynamic control gave the iodopyran 21a; iodoetherification of 20b under kinetic control gave the iodotetrahydrofuran 22. Enantiospecific syntheses of analogues of 24 (Schultz, A. G.; Kirincich, S. J.; Rahm, R. Tetrahedron Lett. 1995, 36, 4551-4554) have been developed. Tetracycle 24 is isomeric with the potent analgesic agent levorphanol, but the bridging of the hydroisoquinoline ring by the hydroxybenzyl unit in 24 is at C(7, isoquinoline numbering) and C(8a) rather than at C(1) and C(4a) as in levorphanol. The key step in the transformation of 7d and 7e to tetracyclic phenolic amines (-)-26 and (+)-28 is the Grewe-type cyclization of 7d to 25b and 7e to 25c. K-i values for the inhibition of binding to the mu-, delta-, and kappa-opioid receptors by (-)-26, (+)-26, (+)-28, (-)-28, and (+)-32 are reported.

  DOI：

  10.1021/jo980921g
• 作为产物：
  描述：

  2-carboethoxy-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid 在 咪唑 、 ruthenium(IV) oxide 、 sodium periodate 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 四氯化碳 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 11.5h， 生成 (+)-(3S)-3,4-dihydro-3-tert-butyldimethylsiloxymethyl-2-methyl-1(2H)-isoquinolinone
  参考文献：
  名称：

  Preparation and Diastereoselective Birch Reduction−Alkylation of Chiral 3,4-Dihydro-1(2H)-isoquinolinones. Enantiospecific Syntheses and Opioid Receptor Affinities of Several Hydro-2,3- dimethyl-1H-7,12a-methanobenzo[6,7]cycloocta[1,2-c]pyridine-9-ols

  摘要：

  Synthetic procedures have been developed to provide 2,3-disubstituted-3,4-dihydro-1(2H)-isoquinones 6, 10, and 15 from (1R,2S)-ephedrine, (1R,2R)-pseudoephedrine, and L-phenylalanine. Birch reduction of 6 and 10 gave enantiomerically related lactam enolates that were alkylated with methyl iodide, allyl bromide, benzyl bromide, p-benzyloxybenzyl bromide, and p-methoxybenzyl bromide to give 7a-7e, 11a, and 11b with diastereoselectivities > 20:1. Birch reduction-methylation of 15 gave 19 with a diastereoselectivity of >35:1. Selective reduction of the disubstituted double bond in 19 with diimide and cleavage of the tert-butyldimethylsilyl ether gave 20b, from which iodoetherification under thermodynamic control gave the iodopyran 21a; iodoetherification of 20b under kinetic control gave the iodotetrahydrofuran 22. Enantiospecific syntheses of analogues of 24 (Schultz, A. G.; Kirincich, S. J.; Rahm, R. Tetrahedron Lett. 1995, 36, 4551-4554) have been developed. Tetracycle 24 is isomeric with the potent analgesic agent levorphanol, but the bridging of the hydroisoquinoline ring by the hydroxybenzyl unit in 24 is at C(7, isoquinoline numbering) and C(8a) rather than at C(1) and C(4a) as in levorphanol. The key step in the transformation of 7d and 7e to tetracyclic phenolic amines (-)-26 and (+)-28 is the Grewe-type cyclization of 7d to 25b and 7e to 25c. K-i values for the inhibition of binding to the mu-, delta-, and kappa-opioid receptors by (-)-26, (+)-26, (+)-28, (-)-28, and (+)-32 are reported.

  DOI：

  10.1021/jo980921g

文献信息

• Preparation and Diastereoselective Birch Reduction−Alkylation of Chiral 3,4-Dihydro-1(2<i>H</i>)-isoquinolinones. Enantiospecific Syntheses and Opioid Receptor Affinities of Several Hydro-2,3- dimethyl-1<i>H</i>-7,12<i>a</i>-methanobenzo[6,7]cycloocta[1,2-<i>c</i>]pyridine-9-ols
  作者：Arthur G. Schultz、Timothy J. Guzi、Erika Larsson、Rainer Rahm、Kshitij Thakkar、Jean M. Bidlack

  DOI：10.1021/jo980921g

  日期：1998.10.1

  Synthetic procedures have been developed to provide 2,3-disubstituted-3,4-dihydro-1(2H)-isoquinones 6, 10, and 15 from (1R,2S)-ephedrine, (1R,2R)-pseudoephedrine, and L-phenylalanine. Birch reduction of 6 and 10 gave enantiomerically related lactam enolates that were alkylated with methyl iodide, allyl bromide, benzyl bromide, p-benzyloxybenzyl bromide, and p-methoxybenzyl bromide to give 7a-7e, 11a, and 11b with diastereoselectivities > 20:1. Birch reduction-methylation of 15 gave 19 with a diastereoselectivity of >35:1. Selective reduction of the disubstituted double bond in 19 with diimide and cleavage of the tert-butyldimethylsilyl ether gave 20b, from which iodoetherification under thermodynamic control gave the iodopyran 21a; iodoetherification of 20b under kinetic control gave the iodotetrahydrofuran 22. Enantiospecific syntheses of analogues of 24 (Schultz, A. G.; Kirincich, S. J.; Rahm, R. Tetrahedron Lett. 1995, 36, 4551-4554) have been developed. Tetracycle 24 is isomeric with the potent analgesic agent levorphanol, but the bridging of the hydroisoquinoline ring by the hydroxybenzyl unit in 24 is at C(7, isoquinoline numbering) and C(8a) rather than at C(1) and C(4a) as in levorphanol. The key step in the transformation of 7d and 7e to tetracyclic phenolic amines (-)-26 and (+)-28 is the Grewe-type cyclization of 7d to 25b and 7e to 25c. K-i values for the inhibition of binding to the mu-, delta-, and kappa-opioid receptors by (-)-26, (+)-26, (+)-28, (-)-28, and (+)-32 are reported.