现代有机合成课件3还原中文

1、3 Reduction 还原反应还原反应3.1 Reduction with complex metal hydrides 金属氢金属氢化物的配合物化物的配合物3.2 Alkoxyaluminate 烷氧基铝化物烷氧基铝化物 reducing agents3.3 Reductions with borohydride 硼氢化物硼氢化物3.4 Borane, aluminum and derivatives 硼烷，铝烷的硼烷，铝烷的衍生物衍生物3.5 Catalytic hydrogenation 催化氢化催化氢化3.6 Dissolving metal reductions 可溶性金属还原可溶

2、性金属还原3.7 Non-metal reducing agents 非金属还原剂非金属还原剂 3.1.1 Mechanism 机理机理 3.1.2 Reduction of carbonyl compounds 羰基化羰基化合物合物 3.1.3 Reduction of non-carbonyl heteroatom functional group 无羰基的杂原子官能团无羰基的杂原子官能团3.1 Reduction with complex metal hydrides3.1.1 Mechanism3.1.2 Reduction of carbonyl compounds酰胺羰基被还原成亚

3、甲基酰胺羰基被还原成亚甲基,-unsaturated carbonyl derivatives 不饱和羰基化合物不饱和羰基化合物Conjugated ketones 共轭酮 often result conjugate reduction(14);conjugated aldehydes 共轭醛 often result 1,2 reduction (13).3.1.3 Reduction of non-carbonyl heteroatom functional group Epoxides 环氧 Ozonides 臭氧化物 Nitriles 氰 Azides 叠氮 Nitro compou

4、nds 硝基化合物 Alkyl halides 卤代烃 Sulfonate esters 磺酸酯 Alkyne alcohols 炔烃3.1.3.1 EpoxidesLithium aluminum hydride delivers the hydride to the less sterically encumbered carbon 位阻小的碳 of an epoxide.3.1.3.2 Ozonides 臭氧化物臭氧化物 and Nitriles 氰氰3.1.3.3 Azides 叠氮化物叠氮化物3.1.3.4 Nitro compounds 硝基化合物硝基化合物3.1.3.5 Alky

5、l halidesBenzylic halides 苄卤苄卤 aliphatic halides 脂肪卤脂肪卤 aryl halides 芳卤芳卤H-作为亲核试剂，作为亲核试剂，SN2反应。反应。3.1.3.6 Sulfonate esters 磺酸酯磺酸酯3.1.3.7 Alkyne alcoholsIn general, the alkene and alkynyl moieties are not reduced by LiAlH4.3.2 Alkoxyaluminate reducing agentsThe reactivity of the LiAlH4 is progressive

6、ly reduced when it is reacted with alcohols. 四氢铝锂的还原四氢铝锂的还原性随着它与醇的反应逐渐减小。性随着它与醇的反应逐渐减小。Example Red-Al 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.芳烃溶剂双甲氧乙氧基铝氢化物双甲氧乙氧基铝氢化物Example 3.3 Reductio

7、ns with borohydride Sodium borohydride 硼氢化钠硼氢化钠 Alternative metal borohydrides (Li, Zn, Ce)其其它金属硼氢化物它金属硼氢化物 Alkoxy- and alkylborohydrides 烷氧基，烷基烷氧基，烷基硼氢化物硼氢化物3.3.1 Sodium borohydrideSodium borohydride is less reactive 还原性较弱还原性较弱 than lithium aluminum hydride, making it a very selective reagent 选择性还原

8、剂选择性还原剂, reducing ketones, aldehydes, and acid chlorides 醛酮酰氯醛酮酰氯 in the presence of other reducible functional groups.Example Aqueous and alcohol solvents 水或醇溶剂水或醇溶剂 are preferred due to the excellent solubility .One of the more important uses of NaBH4 is the reduction of enamines烯胺烯胺, imines亚胺亚胺,

9、and iminium salt亚胺盐亚胺盐, particularly useful in alkaloid 生物碱生物碱 and amino acid 氨基酸氨基酸 syntheses .3.3.2 Alternative metal borohydrides (Li, Zn, Ce)其他的金属硼氢化物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 lacto

10、nes 内酯.It can not reduce acids, nitriles氰基化合物, or nitro compounds硝基化合物.Example 3.3.3 Alkoxy- and alkylborohydrides 烷烷氧基和烷基硼氢化物氧基和烷基硼氢化物 Acyloxyborohydrides 乙氧基硼氢化物乙氧基硼氢化物 Super Hydrides 超级氢化物超级氢化物 The selectrides 三仲丁基硼氢化物三仲丁基硼氢化物 Sodium cyanoborohydrides 氰基硼氢化氰基硼氢化钠钠3.3.3.1 Acyloxyborohydrides 酰氧基硼氢

11、化物酰氧基硼氢化物Acyloxyborohydrides are remarkably selective.非常高的选择性非常高的选择性3.3.3.2 Super Hydrides 超氢化物超氢化物The most common use of Super-Hydrides is probably for the reductive dehalogenation of alkyl halides. 用于用于卤代烃的脱卤化反应。这个是氢负离子作为亲核试卤代烃的脱卤化反应。这个是氢负离子作为亲核试剂的剂的SN2反应，印证了这类化合物的强还原性。反应，印证了这类化合物的强还原性。3.3.3.3 The

12、 selectrides3.3.3.4 Sodium cyanoborohydridesA 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。非常稳定，酸性条件下仍能稳定存在。还原氨化反应，亚胺的还原。还原氨化反应，亚胺的还原。酸性条件下进行酸性条件下进行+BrBr+BrBr+Br2KOHH2/ NiBlanc Chloromethylation Reaction （Blanc氯甲基化反应氯甲基化反应 ）Blanc 氯甲基化反应是指在Lewis 酸催化下,芳香族化合 物和 HC

13、l ,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 OO1，3-丁二烯和顺丁烯二酸酐为原料OOBaeyer- VilligerOOHOOCOEtOOCEtOOCEtOOCHOOCHOOCP, HIOHOHOOO+OOOOOEtOOCHOOCHOOCOHOHOOO+OOOLiAlH4Et2OPHI1) O32) H2O2CH3CH2OHH+, EtOOCEtOOCCH3ONaCH3OH1) O

14、H-2) H+3) CH3COOOHOO布洛芬布洛芬3.4 Borane 硼烷硼烷, aluminum hydride and derivatives 氢化铝及其衍生物氢化铝及其衍生物 Borane Aluminum hydride and derivatives3.4.1 BoraneDiborane 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 ineffect

15、ive for the reduction of esters and reacts with alkene.对酯的还原和与烯烃反应效果不佳。 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。三氯乙醛容易还原。3.4.2 Aluminum hydrideIts most common use is the selective 1,2-reduction of conj

16、ugated aldehydes, ketones and esters.选择性的选择性的进行进行1,2还原对于共轭的醛酮和酯。还原对于共轭的醛酮和酯。果蝇信息素合成中间体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位容易。3.4.3 Diisobutylaluminum hydride 二异丁二异丁基氢化铝基氢化铝将酰胺还原成醛将酰胺还原成醛将酯还原成醛3.5 Catalytic hydrogenation 催化氢化催化氢化 Heterogeneous 非均相非均相: catalyst insoluble 不溶不溶 in the reactio

17、n medium 反应介质反应介质. Homogeneous 均相均相: catalyst soluble in the reaction medium. 3.5.1 Typycal heterogeneous hydrogenation catalysts3.5.2 Heterogeneous hydrogenation reductionsRCH=CHR + H2RCH2CH2RcatalystuCatalyst 催化剂催化剂: Pt, Pd, NiuPd/C: Palladium on carbon 钯负载在碳上钯负载在碳上uRaney Ni: Al-Ni reacts with NaO

18、HuHeat of hydrogenation: higher H, higher potential energy of alkeneuSyn addition 顺式加成顺式加成Why syn addition?H2HHHHMechanism of hydrogenation:uAlkyne is more reactive than alkene;uLindlar catalyst: Pd/CaCO3uSyn addition product: cis-alkeneHow to get trans-alkene 反式烯烃反式烯烃?3.5.3 Homogeneous CatalysisSol

19、uble homogeneous catalysts offer the best route for asymmetric induction 不对称氢化不对称氢化 in catalytic hydrogenation, especially for alkenes.Wilkinsons catalystExample A common way to generate a chiral catalyst involves a modification of Wilkinsons catalyst.One of the more important applications of chiral

20、 hydrogenation catalysts is the preparation of chiral amino acids.3.6 Dissolving metal reductionsReduction of carbonyl compounds 羰基化合物羰基化合物Reduction of alkynes 炔烃炔烃Hydrogenolysis 氢解氢解Birch reduction 还原还原The Benkeser reductionReduction with zinc and tin 锌和锡锌和锡Reduction with aluminum 铝铝Electrolytic re

21、ductions 电解还原电解还原3.6.1 Reduction of carbonyl compoundsClemmensen 还原还原3.6.2 Reduction of alkynes 非末端炔烃非末端炔烃Anhydrous ammonia (NH3) is a liquid below -33 C Alkali metals 碱金属碱金属 dissolve in liquid ammonia and function as reducing agents 有还原剂的作用有还原剂的作用Alkynes are reduced to trans-alkenes with sodium 钠钠

22、or lithium 锂锂 in liquid ammoniaThe reaction involves a radical anion 自由基负离子自由基负离子 intermediateNaRCCRNH2RCCRHCCRHRHCRCRHRCCRHNaCCRHRvinyl radical I IIanion radicalMechanism of dissolved metal reduction:3.6.3 Hydrogenolysis 氢解氢解Dissolving metal conditions are particularly useful for the cleavage of O-

23、benzyl and N-benzyl deritives.苄氧基，苄氮基，去保护。苄氧基，苄氮基，去保护。开环丙烷环开环丙烷环除去砜基除去砜基氧位于位阻小的一边氧位于位阻小的一边3.6.4 Birch reduction与芳环共轭的双键会被还原掉与芳环共轭的双键会被还原掉An important modification of Birch reduction is replacing lithium with calcium, called Benkeser reduction.总体和总体和Birch一样，安全性更好。一样，安全性更好。3.6.5 The Benkeser reduction3.6.6 Reduction with zinc and tinZinc in acetic acid is a very effective reagent