Synthesis of Optically Pure Enantiomers Using Chiral Ureas

使用手性脲合成光学纯对映体

• 批准号: 03640438
• 负责人: YAMADA Kazutoshi
• 金额: $ 1.34万
• 依托单位: CHIBA University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03640438/
• 关键词: Asymmetric Aldol reaction; Asymmetric Diels-Alder reaction; Michael addition; Imidazolidinone; exo-methylenehydantoin; Chiral derivatizing agent; Type II photocyclization; カルボジイミド; 不斉アルド-ル反応; 不斉ディ-ルス・アルダ-反応; 1.4ー付加反応

Using Chiral urea derivatives, the following diastereoselective synthesis and a convenient separation of diastereomers by a conventional column chromatography were accomplished.(1) Diastereoselective aldol addition reaction using chiral acylureas; This method was applied to the two step synthesis of (+) Blastmaycinolactol.(2) Chiral carbodiimide as an effective chiral derivatizing agent; N,N'-bis[(s)-l-phenylethyl]- carbodiimide was found to be a very useful chiral derivatizing agent, which made an easy separation of diastereomers of alpha-amino acids and alpha-halo acids by a conventional column chromatography.(3) Highly enantioselective Aldol reaction using imidazolidinone as a new chiral Auxiliary; Aldol addition reaction of almost perfect stereo control (>99% diastereoselectivity) was developed.(4) Chiral hydantoin as a new dienophile for Diels-Alder Reaction; A new synthetic method of chiral exo-methylenehydantoin from chiral carbodiimides and alpha-ketoacids was established and the exo-methylenehydantoin thus obtained was applied for Diels-Alder reaction to prepare chiral bicyclic alpha-amino acid derivatives.(5) Conjugated addition reaction of alkylaluminum compounds to exo-methylenehydantoin; Mono and Double conjugated additions of aluminum reagents to exo-methylenehydantoin were found out and this two modes of addition was effectively controlled.(6) Three component coupling reaction carbodiimide, monomethyl maleate, and alcohol; This coupling afforded N-(aminocarbony)aspartates.(7) Asymmetric type II photocyclization of acrylylureas; It was found that the stereochemistry of the carbon atom where a hydrogen atom to be abstracted in type II photocyclization was retained to give a chiral beta-lactam.

使用手性脲衍生物，完成了以下非对映选择性合成和常规柱层析的方便的非对映体分离。(1)手性酰基脲的非对映选择性醛醇加成反应；该方法应用于（+）blastmaycinolacol的两步法合成。(2)手性碳二亚胺作为一种有效的手性衍生剂；N，N′-双[(s)-l-苯乙基]-碳二酰亚胺是一种非常有用的手性衍生化剂，它可以很容易地用常规柱层析法分离α -氨基酸和α -晕酸的非对映体。(3)咪唑烷酮为新型手性助剂的高对映选择性Aldol反应；建立了几乎完全立体控制（bb0 ~ 99%非对映选择性）的醛醇加成反应。(4)手性乙酰胆碱作为Diels-Alder反应的新亲二酚；建立了以手性碳二亚胺和-酮酸为原料合成手性外亚甲酰脲的新方法，并将所得的外亚甲酰脲用于Diels-Alder反应制备手性双环-氨基酸衍生物。(5)烷基铝化合物与外亚甲基乙酰妥英的共轭加成反应；发现了铝试剂对外甲基乙酰脲的单、双共轭加成，并对这两种加成方式进行了有效控制。(6)碳二亚胺、马来酸单甲基与醇的三组分偶联反应；这种偶联产生N-（氨基碳）天冬氨酸。(7)丙烯脲类化合物的不对称II型光环作用；结果发现，在II型光环反应中，碳原子的立体化学反应被保留，其中一个氢原子被抽离，得到手性β -内酰胺。

项目成果

Wongsiri SANKHAVASI: "New Chiral Auxiliary;4,5-Diphenyl-1-nethyl-2-imidazlidinone.Its Utility in Highly Enantio-selective Aldol Reaction." Bill.Chem.Soc.Jpn.64. 935-937 (1991)

Wongsiri SANKHAVASI：“新型手性助剂；4,5-二苯基-1-甲基-2-咪唑啉酮。其在高度对映选择性羟醛反应中的应用。”

Wongsiri SANKHAVASI: "Chiral Hydantoin;A New Dienophile for Diels-Alder Reaction." Bill.Chem.Soc.Jpn.65. 3195-3197 (1992)

Wongsiri SANKHAVASI：“手性乙内酰脲；第尔斯-阿尔德反应的新亲双烯体。”

Wongsiri SANKHAVASI: "Non-catalyzed Conjugated Addition Reaction of Alkyl-aluminum Compounds to 5-Methylene-2-,4-imidazo-idinedione Derivative." Bill.Chem.Soc.Jpn.65. 3195-3197 (1992)

Wongsiri SANKHAVASI：“烷基铝化合物与 5-亚甲基-2-,4-咪唑并-啶二酮衍生物的非催化共轭加成反应”。

Wongsiri Sankhavasi: "New Chiral Auxiliary;4,5ーDiphenylー1ーmethylー2ーimidazolidinone" Bull.Chem.Soc.Jpn.64. 1425-1427 (1991)

Wongsiri Sankhavasi：“新手性助剂；4,5－二苯基－1－甲基－2－咪唑啉酮”Bull.Chem.Soc.Jpn.64（1991）。

Wongsiri Sankhavasi: "Chiral Hydantoin;A New Dienophile for DielsーAlder Reaction" Bull.Chem.Soc.Jpn.65. (1992)

Wongsiri Sankhavasi：“手性乙内酰脲；一种新的 Dienophile for Diels-Alder Reaction”Bull.Chem.Soc.Jpn.65 (1992)。