现代有机合成课件-3还原中文

Example
Aqueous and alcohol solvents 水或醇溶剂 are preferred due to the excellent solubility .
One of the more important uses of NaBH4 is the reduction of enamines烯胺, imines亚胺, and iminium salt亚胺盐, particularly useful in alkaloid 生物碱 and amino acid 氨基酸 syntheses .
3.5.3 Homogeneous Catalysis
性随着它与醇的反应逐渐减小。
Example
Red-Al
双甲氧乙氧基铝氢化物
The reducing power of Red-Al is close to lithium aluminum hydride.和四氢铝锂近似 Advantages: Good thermal 热 stability and easy solubility in aromatic hydrocarbon.芳烃溶剂
3.1.3.1 Epoxides
Lithium aluminum hydride delivers the hydride to the less sterically encumbered carbon 位阻小的碳 of an epoxide.
3.1.3.2 Ozonides 臭氧化物 and Nitriles 氰
酸性条件下进行
还原氨化反应，亚胺的还原。
+ Br Br
+

+
Br2
Br Br
KOH
H2/ Ni

Blanc Chloromethylation Reaction （Blanc氯甲基化反应 ）
Blanc 氯甲基化反应是指在Lewis 酸催化下,芳香族化合 物和 HCl , 甲醇或氯甲醚反应 , 在芳香族化合物中引入氯甲 基,这一反应在有机合成 和化工生产中有重要的应用. HCl的作用： （1）提供氢离子让甲醛质子化，然后对苯环进攻； （2）提供氢离子让苯甲醇中间体羟基质子化； （3）提供氯离子对质子化的苯甲醇进攻发生SN2反应
O O
O O O EtOOC EtOOC EtOOC HOOC HOOC O P, HI OH OH O O
1，3-丁二烯和顺丁烯二酸酐为原料
O HOOC
Baeyer- Villiger
O
O + O O
O + O O 1) O3 2) H2O2 O EtOOC HOOC HOOC 1) OH2) H+ 3)
3 Reduction 还原反应
3.1 Reduction with complex metal hydrides 金属氢
化物的配合物
3.2 Alkoxyaluminate 烷氧基铝化物 reducing agents 3.3 Reductions with borohydride 硼氢化物 3.4 Borane, aluminum and derivatives 硼烷，铝烷的
3.1.3.7 Alkyne alcohols
In general, the alkene and alkynyl moieties are not reduced by LiAlH4.
3.2 Alkoxyaluminate reducing agents
The reactivity of the LiAlH4 is progressively reduced when it is reacted with alcohols. 四氢铝锂的还原
3.4.3 Diisobutylaluminum hydride 二异丁
基氢化铝
将酰胺还原成醛
将酯还原成醛
3.5 Catalytic hydrogenation
催化氢化
• Heterogeneous 非均相: catalyst insoluble 不溶 in the reaction medium 反应介质.
3.1.2 Reduction of carbonyl compounds
酰胺羰基被还原成亚甲基
,-unsaturated carbonyl derivatives 不饱和羰基化合物
Conjugated ketones 共轭酮 often result conjugate reduction(14);conjugated aldehydes 共轭醛 often result 1,2 reduction (13).
衍生物
3.5 Catalytic hydrogenation 催化氢化 3.6 Dissolving metal reductions 可溶性金属还原 3.7 Non-metal reducing agents 非金属还原剂
3.1 Reduction with complex metal hydrides
3.1.3 Reduction of non-carbonyl heteroatom functional group
• • • • • • • • Epoxides 环氧 Ozonides 臭氧化物 Nitriles 氰 Azides 叠氮 Nitro compounds 硝基化合物 Alkyl halides 卤代烃 Sulfonate esters 磺酸酯 Alkyne alcohols 炔烃
硼氢化物
3.3.1 Sodium borohydride
Sodium borohydride is less reactive 还原性较弱 than lithium aluminum hydride, making it a very selective reagent 选择性还原剂, reducing ketones, aldehydes, and acid chlorides 醛酮酰氯 in the presence of other reducible functional groups.
Catalyst 催化剂: Pt, Pd, Ni Pd/C: Palladium on carbon 钯负载在碳上 Raney Ni: Al-Ni reacts with NaOH Heat of hydrogenation: higher ∆H, higher potential energy of alkene Syn addition 顺式加成
卤代烃的脱卤化反应。这个是氢负离子作为亲核试 剂的SN2反应，印证了这类化合物的强还原性。
3.3.3.3 The selectrides
3.3.3.4 Sodium cyanoborohydrides
A remarkably stable regent that does not decompose in acid solution. 非常稳定，酸性条件下仍能稳定存在。
3.4.1 Borane
由于硼烷的缺电子特性，强路易斯酸，能够与富电子的原子配位结合。 在还原羰基时，增加羰基的电子云密度有利于反应的进行，比如新戊醛反应 比三氯乙醛容易还原。
Diborane 乙硼烷 is a potent 强效的 reducing agent 还原试 剂 for aldehydes醛, ketones酮, lactones内酯, epoxide环氧, acids酸, tertiary amides 三级酰胺 and nitriles腈. It is ineffective for the reduction of esters and reacts with alkene.
Example
3.3 Reductions with borohydride • Sodium borohydride 硼氢化钠 • Alternative metal borohydrides (Li, Zn, Ce)其
它金属硼氢化物
• Alkoxy- and alkylborohydrides 烷氧基，烷基
3.3.2 Alternative metal borohydrides (Li, Zn, Ce)其他的金属硼氢化物
LiBH4 is a more powerful reducing agent 更强的还 原剂 than NaBH4. It can reduce aldehydes, ketones, acid chloride, epoxides环氧, esters酯 and lactones 内酯.It can not reduce acids, nitriles氰基化合物, or nitro compounds硝基化合物.
对酯的还原和与烯烃反应效果不佳。
3.4.2 Aluminum hydride
果蝇信息素合成中间体
氢化铝作为路易斯 酸与氧配位结核性 强，同时空间距离 决定了负氢转移到 羰基碳比β位容易 。
It’s most common use is the selective 1,2-reduction of conjugated aldehydes, ketones and esters.选择性的 进行1,2还原对于共轭的醛酮和酯。
• 3.1.1 Mechanism 机理 • 3.1.2 Reduction of carbonyl compounds 羰基化
合物
• 3.1.3 Reduction of non-carbonyl heteroatom functional group 无羰基的杂原子官能团
3.1.1 Mechanism
• Homogeneous 均相: catalyst soluble in the reaction medium.
3.5.1 Typycal heterogeneous hydrogenation catalysts
3.5.2 Heterogeneous hydrogenation reductions
O O O CH3CH2OH H+, O CH3COOOH O O EtOOC EtOOC CH3ONa CH3OH LiAlH4 Et2O OH OH P HI
布洛芬
3.4 Borane 硼烷, aluminum hydride and derivatives 氢化铝及其衍生物
• Borane • Aluminum hydride and derivatives
3.1.3.3 Azides 叠氮化物
3.1.3.4 Nitro compounds 硝基化合物
3.1.3.5 Alkyl halides
Benzylic halides 苄卤> aliphatic halides 脂肪卤> aryl halides 芳卤
H-作为亲核试剂，SN2反应。
3.1.3.6 Sulfonate esters 磺酸酯
Example
3.3.3 Alkoxy- and alkylborohydrides 烷
氧基和烷基硼氢化物
• • • • Acyloxyborohydrides 乙氧基硼氢化物 Super Hydrides 超级氢化物 The selectrides 三仲丁基硼氢化物 Sodium cyanoborohydrides 氰基硼氢化
钠
3.3.3.1 AcyloxyborohyLeabharlann Baidurides 酰氧基硼氢化物
Acyloxyborohydrides are remarkably selective.
非常高的选择性
3.3.3.2 Super Hydrides 超氢化物
The most common use of Super-Hydrides is probably for the reductive dehalogenation of alkyl halides. 用于
Why syn addition?
Mechanism of hydrogenation:
Alkyne is more reactive than alkene; Lindlar catalyst: Pd/CaCO3 Syn addition product: cis-alkene
How to get trans-alkene 反式烯烃?