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1、第二节 取代反应,F-C Alkylations,Various side reactions such as isomerization,fragmentation and dealkylation together with side-chain and positinal rearrangements often occurred.,Sugita et.al.: By addition additives CuCl2 or Cu2Cl2 or declain to obtain high regioselectivity.,Ritter reaction,Tertiary alcohol
2、s tend to react without rearrangement while secondary alcohols are liable to do so. Primeay alcohols normally fail to react with nitriles except the benzylic examples.,either alcohol isomer gave mainly the amine product produced by axial attack on the carbon.,Stereo-selective,1)硅烷还原反应,2) 催化氢化,脱水ROOC
3、CF3,第三节 还原反应,3) 单电子还原,4) 自由基还原,-Permit the deoxygenation of most types of alcohols and the monodeoxygenation of 1,2 and 1,3-diols, these processes are limited only by those side-reactions (intramolecular cyclizations or fragmentations) of carbon radicals which can successfully compete with H-abstrac
4、tion from an efficient donor(R3SnH), and frequently provide the method of choice for deoxygenation in polyfunctionalized systems bearing groups sensitive to hydride or dissolving metal reagents. Review: Hartwig, W., Tetrahedron, 1983, 39, 2609; Barton, D. H. R. and Motherwell, W. B., Pure Appl. Chem
5、., 1981, 53, 15.,Wagner-Meerwein rearrangement,第四节 其他反应,Pinacol rearrangement,各类邻二醇 不对称取代的二醇中，生成更稳定碳正离子的碳上的羟基更容易质子化后离去； 碳正离子相邻碳上能够稳定碳正离子的基团优先迁移； 迁移基团与离去基团处于反位更易于重排。,加成反应,合成参见：,Via ene reaction Comprehensive Organic Synthesis, 2, 538; Via oxidative cleavage of alkenes Comprehensive Organic Synthesis,
6、 7, 541; Via carboxylic acids Comprehensive Organic Synthesis, 8, 235; Via enantiomeric reduction of carbonyl compounds Comprehensive Organic Synthesis, 8, 185; Via epoxide reduction Comprehensive Organic Synthesis, 8, 871; Via hydrogen transfer Comprehensive Organic Synthesis, 8, 110; Via metal hyd
7、ride Comprehensive Organic Synthesis, 8, 1-22; Via organoboranes Comprehensive Organic Synthesis, 3, 793; Via organocerium compounds Comprehensive Organic Synthesis, 1, 231; Via reduction of hydroperoxides Comprehensive Organic Synthesis, 8, 396; Via substitution processes Comprehensive Organic Synt
8、hesis, 6, 1-28;,第五章 羰基化合物的反应,第一节 Enolate 的化学,参考文献：,Formation of Enolates: Comprehensive Org. Syn., Vol. 2, 99. Enolate Alkylations: Comprehensive Org. Syn., Vol. 3, 1. Aldol Condensation: Comprehensive Org. Syn., Vol. 2, 133, 181 and 239. Reformatsky Reaction: Comprehensive Org. Syn., Vol. 2, 277. A
9、cylation of Enolates: Comprehensive Org. Syn., Vol. 2, 796. Enol Ethers: Comprehensive Org. Syn., Vol. 2, 595 and 629. Metalloenamines: Comprehensive Org. Syn., Vol. 2, 475. Hydrazones: Comprehensive Org. Syn., Vol. 2, 503.,a. Estimation of p Ka,- an increase in acidity of H results in a faster depr
10、otonation (kinetic effect) as well as a stabilization of anion formed (thermodynamic effect)., 5-1-1 一些基本问题,b. Ketone-Enol Tautomerism,If a compound has a vinyl spacer, the reactivity parallels that of the parent compound. 1,3-Cyclohexadione in its enol form is a vinylogous carboxylic acid and it ex
11、hibits many properties of a RCOOH, including low p Ka, O-alkylation.,c. Enolate Structure,- Actually exist as higher aggregates in solution: dimer-tetramer. - Originally suggested by House J. Org. Chem. 1971, 36, 2361. - Supported by NMR studies: Jackman Tetrahedron 1977, 33, 2737. - Confirmed by X-
12、ray: Dunitz Helv. Chim. Acta 1981, 64, 2617.,Use of a base which stoichiometrically deprotonates the ketone completely: (i.e. Keq 100), 5-1-2 合成,Therefore, a good deprotonation (essentially all ketone deprotonated) Note: need to have pKa difference of 2 pKa units to get Keq = 100.,- Aggregates: Will
13、iard J. Org. Chem. 1993, 58, 1. - Other widely used bases:,Reviews: Conia Rec. Chem. Prog. 1963, 24, 43. House Rec. Chem. Prog. 1967, 28, 99. Fleming Chimica 1980, 34, 265. Fleming Synthesis 1982, 521. Fleming Synthesis 1977, 509. dAngelo Tetrahedron 1976 , 32, 2979 (Methods for regiospecific enolat
14、e generation). Evans Asymm. Synthesis, Morrison, Ed., Vol. 3, 1.,Kinetic and Thermodynamic Enolates,Regiospecific Enolate Generation,In the above case, the D2,3 enolate cannot be cleanly obtained directly, but other approaches to this have been developed.,Representive enolate selectivities:,Enantio-
15、 or diastereoselective protonation of ketone enolates： deprotonation: Majewski Can. J. Chem. 1994, 72, 1699. Simpkins Tetrahedron Lett. 1992, 33, 8141&1989, 30, 7241. protonation: Fehr Angew. Chem., Int. Ed. Eng. 1994, 33, 1764.,Cyclic Carbonyl Compounds - site of deprotonation - enolate geometry fi
16、xed,Ireland Transition State Model for Deprotonation J. Am. Chem. Soc. 1976, 98, 2868.,Stereoselective Enolate Generation,- ASIDE: Geometry of enolate can be determined by Claisen rearrangement:,- Claisen rearrangement known to proceed through chair-like T.S.:,Acyclic Ketones,Thermodynamic enolate formation,Acyclic Esters (Similar to ketones):,Otera Synlett 1994, 213.,Silyl Ketene Acetals,Acyclic Amides
