高等有机合成.ppt

高等有机合成AdvancedOrganicSynthesis 绪论 一 有机合成的历史回顾二 有机合成化学的发展趋势三 学习内容和方法四 重要参考书及期刊五 课程安排 一 有机合成的历史回顾 1 尿素的合成 1828年 德国化学家Wohler 有机化学的开始 2 颠茄酮的合成 1 1902年 德国化学家Willstatter 1915年获Noble化学奖 21steps overallyield0 7 2 1917年 英国化学家Robinson 1947年获Noble化学奖 3steps overallyield90 Robinson为什么能是发现这条合成路线 MannichReaction 1912 3 维生素B12的合成 Woodward 1977年 在Woodward及Eschenmoser领导下 经过两个实验室 100多位科学家的共同努力 于1977年完成了维生素B12的全合成工作 将有机合成作为一种艺术展现在世人面前 因在1945 1954年人工合成了奎宁 类固醇 马钱子碱 羊毛甾醇 麦角碱等近20种复杂天然产物而1965年获Noble化学奖 E J Corey 1990年获Noble化学奖 如果说Woodward一生奋斗的成就是将有机合成作为一种艺术展现在世人面前 那么Corey则是将有机合成从艺术转变成为科学的一个关键人物 他的逆合成分析是现代有机合成化学的重要基石 推动了20世纪70年代以来整个有机合成领域的蓬勃发展 逆合成分析 Retrosyntheticanalysis Woodward 1981 红霉素的全合成 Y Kishi 1987 海葵毒素的全合成 S L Schreiberetal 1993 FK 1012的全合成 K C Nicolaou S L Schreiber 1994 紫杉醇 Taxol 的全合成 5 K C Nicolaou S L Schreiber K C Nicolaou etal Theartandscienceoftotalsynthesisatthedawnoftwenty firstcentury Angew Chem Int Ed Engl 2002 39 44 S L Schreiber etal Target orientedanddiversity orientedorganicsynthesisindrugdiscovery Science 2000 287 1964 高立体选择性 HighStereoselectivity 原子经济性反应 AtomEconomicalReaction 绿色化学 GreenChemistry 二 有机合成化学的发展趋势 1 新试剂 新反应 新方法的发现永无止境 Epibatidine的研究 Y OTf 3 catalyzednovelMannichreactionofN alkoxy carbonylpyrroles formaldehydeandprimaryaminehydrochlorides C X Zhuan J C Dong T M Cheng R T Li TetrahedronLetters 2001 43 3 461 463 Aldol缩合反应的研究 2 与生命科学和材料科学的联系越来越紧密 三 学习内容和方法 内容 1 对重要的基础有机反应要能够熟练运用 新化合物的合成 比葫芦画瓢 逆合成分析 跟踪文献 尽可能将最新的试剂 反应和方法应用于自己的研究工作中 3 学习别人的思路 创造性地借鉴和运用 方法 四 重要参考书及期刊 参考书 F A Carey著 王积涛译 高等有机化学 B 反应与合成 高等教育出版社 1986 岳保珍 李润涛 有机合成基础 北京医科大学出版社 2000 吴毓林 姚祝军 现代有机合成化学 科学出版社 2001 W Carruthers著 李润涛等译 有机合成的一些新方法 河南大学出版社 1991 黄宪 王彦广 陈振初 新编有机合成化学 化学工业出版社 2003 王咏梅等 高等有机化学习题解答 南开大学出版社 2002 DaleL Boger ModernOrganicSynthesis TheScrippsResearchInstitute TsriPress 1999 ComprehensiveOrganicSynthesis Vol 1 9 期刊 Angew Chem Int Ed J Am Chem Soc J Org Chem Org LettersChem Commun TetrahedronTetrahedronLetters TetrahedronAsymm SynthesisSynlett 11 Synth Commun 12 Eur J Chem 13 Eur J Org Chem 14 Heterocyclics15 J HeterocyclicChem 16 J Med Chem Bioorg Med Chem Bioorg Med Chem Lett Eur J Med Chem 20 J Comb Chem 五 课程安排 进度安排2 讲授原则复习老反应 补充新反应 重点讲进展 强调学思路 考试1 写综述一篇 近5年的进展 40 2 笔试 60 Chapter2FormationofCarbon CarbonSingleBonds 一 GeneralPrinciples 烷化反应 E 烷化剂缩合反应 E 醛 酮 酯等Michael加成 E Mannich反应 二 影响反应的主要因素 a 反应底物 Substrate NO2 COR SO2R CN CO2R Ph SOR A和B至少要有一个是EWG A和B应该能使其 碳上的H活化的基团 通常为吸电子基 ElectronwithdrawgroupEWG b 碱 Base 常用的碱 Ph3C Me2CH 2N EtO OH R3N碱的选择取决于底物的反应活性 理想的碱 碱性强 亲核性弱 并不进攻那些较敏感的基团 另外能溶于非极性溶剂中 c 溶剂 Solvent Solvent O alkylationC alkylation 反应速度 常用的非质子极性溶剂 polaraproticsolvent DMFDMSOHMPA d 亲电试剂 Electrophilicreagent 所有能与负碳离子发生反应的碳正离子或分子 例 RX R SO3H RCO2Et RCOR 这四种影响因素之间是相互联系 相互影响的 在分析一个具体反应时 应该综合分析考虑这四种影响因素 三 烷基化反应 Alkylation 1 O alkylation C alkylation Example1 Example2 Degreeofsubstitutionofalkylatingagent Example3 2 区域选择性 Regioselectivity 区域选择性受热力学控制和动力学控制的反应条件影响很大 热力学控制条件下主要生成取代基较多的烯醇 动力学控制条件下主要生成取代基较少的烯醇 Example1 Example2 3 立体选择性 Steroselectivity 烯醇化合物的立体选择性形成 将为不对称合成提供平台 Example1 Example2 Example3 Example4 4 二羰基化合物的 烷基化反应 Alkylationof1 3 dicarbonylcompounds J Am Chem Soc 1974 90 1082 1963 85 3237 1965 87 82 Example1 Example2 Example3 继承与发展 5 芳基卤化物与烯醇盐的反应 Reactionsofaromatichalidewithenolates Example Mechanism 关键是要有形成苯炔的条件 6 酮和酯的烷基化反应 Alkylationsofketonesandesters 避免Aldol缩合反应发生的方法 烷化剂要待酮完全转化为烯醇式后再加入 常用的碱 NaNH2 KNH2 NaH Ph3CNa等 有副产物 LDA LTMP LHMDS等效果很好 Example1 Example2 不对称酮的选择性烷基化反应 Selectivealkylationofasymmetricketones 在一个 位引入一个活化基 略 如 DieckmannReaction Claisencondensation 制成结构专属性的烯醇负离子 在取代基较多的 位烷基化 烯醇硅醚法 碱性条件 酸性条件 在取代基较少的 位烷基化 烯胺法 StorkEnamineSynthesis 通常 用活泼的卤代烷 可以高产率生成C 烷基化产物 但对于一般的卤代烃 C 烷基化产物收率较底 若用LDA在低温下反应 则对各种卤代烃均可得到高收率的C 烷基化产物 对于不对称酮 主要在取代基较少的 位发生烷基化 Example1 Example2 7 对映选择性烷基化反应 Enantioselectivealkylations 利用手性胺 利用二甲基肼 扩展 二甲基腙锂化合物的另一应用 二甲基腙锂化合物容易转化成有机铜化合物 而有机铜化合物在C C键的形成中很有用 利用SAMP和RAMP 若用RAMP 则得到另一种对映异构体 羧酸的 不对称烷基化 Example 8 极性翻转 Umpolung 俞凌翀 刘志昌 极性转换及其在有机合成中的应用 科学出版社 1991 Example1安息香缩合 Example2醛氰醇法 Example31 3 二噻烷法 不易发生Michael加成反应 Example4乙基乙硫甲基亚砜法 1 4 二酮 四 缩合反应 Condensation AldolReactionMichaelAdditionMannichReactionClaisenCondensationDieckmannCondrnsationDarzen sReactionReformatslyreaction AldolReaction condensation 1 经典Aldol反应的两大缺点 不同醛 酮之间的反应常得到混合产物 立体选择性差 2 定向醇醛缩合反应 DirectedAldolcondensation Metood1PreformedLithiumEnolates Z enolatesgivepredominantlysyn orthreo aldolproducts thermodynamicenolates E enolatesgivepredominantlyanti orerythro aldolproducts kineticenolates Example1 StericsizeofR1affectsdiastereoselectivity OriginofDiastereoselectivity a Z enolates DiastereoselectivityforZ enolate givingsynaldolproduct ismaximizedwhenR1andR3arestericallydemanding R1 R3interactionismaximized Diastereoselectivityalsoincreasesasmetalischangedtoboron ThisisattritubtedtoatighterT S B Obondshorter soR1 R3stericinteractionsaremagnifiedinT S forantiproduct WhenR2isverylargetheR3 R2gaucheinteraction R1 R31 3 diaxialinteraction Why b E enolates DiastereoselectivityincreasesasR1andR3becomestericallylarge andaswitchtotheboronenolatewillincreaseselectivity DiastereoselectivitymayswitchwhenR2isverylarge Why EffectofR1 EffectofR3 EffectofR2 Metood2PreformedBoronEnolates a Z enolatePreparationandReactions b E enolatePreparationandReactions Originallydifficulttocontrolbut c Examplesofmorerecentmethodstocontrolboronenolategeometry AldolCondensationwithChiralEnolates TienolatepromotedEvansaldol non Evanssynaldol Chelatedandnon chelatedTienolates Metood3Acid CatalysedDirectedAldolReactions 该方法是在酸性条件下反应 但立体选择性较差 3 有机小分子催化醇醛缩合反应 SmallOrganicMoleculesCatalystedAldolReactions NovelSmallOrganicMoleculesforaHighlyEnantioselectiveDirectAldolReaction J AM CHEM SOC 2003 125 5262 5263 ZhuoTang FanJiang Luo TingYu XinCui Liu ZhuGong Ai QiaoMi Yao ZhongJiang andYun DongWu KeyLaboratoryforAsymmetricSynthesisandChirotechnologyofSichuanProvince ChengduInstituteofOrganicChemistry ChineseAcademyofSciences Chengdu 610041 China CollegeofChemicalEngineering SichuanUniVersity Chengdu 610065 China andStateKeyLaboratoryofMolecularDynamicsandStableStructures CollegeofChemistryandMolecularEngineering PekingUniVersity Beijing 100871 China 2 MichaelAdditionReaction Applications Synthesisof1 5 dicarbonylcompounds GeneralScheme Development AsymmetryMichaelAdditionReaction 手性金属配位化合物催化 MacmillanGroup sWork SmallOrganicMoleculecatalyzedasymmetricMichaelreactions TheFirstEnantioselectiveOrganocatalyticMukaiyama MichaelReaction S P Brown N C Goodwin andD W C MacMillan J Am Chem Soc 2003 125 5 1192 1194 3 MannichReaction GeneralScheme 胺组份氨 伯胺 仲胺 醛组份HCHO PhCHO RCHO 可分别发生三 双 单Mannich反应 活泼H组份 醛 酮 活泼亚甲基化合物 酚类化合物 杂环 炔等 Example2 Example1 Development AsymmetryMannichReaction Lewisacid catalyzedasymmetricMannichreactions a Fujii A Hagiwara E Sodeoka M J Am Chem Soc 1999 121 5450 b Ishitani H Ueno M Kobayashi S J Am Chem Soc 2000 122 8180 c Ishihara K Miyata M Hattori K Yamamoto H J Am Chem Soc 1994 116 10520 d Ishitani H Ueno M Kobayashi S J Am Chem Soc 1997 119 2060 e Ferraris D Yong B Dudding T Leckta T J Am Chem Soc 1998 120 4548 f Ferraris D Young B Cox C Dudding T Drury W J III Ryzhkov L Taggi A E Lectka T J Am Chem Soc 2002 124 67 g Kobayashi S Hamada T Manabe K J Am Chem Soc 2002 124 5640 a Notz W Sakthivel K Bui T Zhong G Barbas C F IIITetrahedronLett 2001 42 199 b Juhl K Gathergood N Jorgensen K A Angew Chem Int Ed 2001 40 2995 c Yamasaki S Iida T Shibasaki M Tetrahedron1999 55 8857 d List B J Am Chem Soc 2000 122 9336 e Co rdova A Notz W Zhong G Betancort J M Barbas C F IIIJ Am Chem Soc 2002 124 1842 f Co rdova A Watanabe S i Tanaka F Notz W Barbas C F IIIJ Am Chem Soc 2002 124 1866 SmallOrganicMoleculecatalyzedasymmetricMannichreactions TheDirectandEnantioselective One Pot Three Component Cross MannichReactionofAldehydes Angew Chem Int Ed 2003 42 3677 3680 Y Hayashi W Tsuboi I Ashimine T Urushima Dr M ShojiDepartmentofIndustrialChemistry FacultyofEngineeringTokyoUniversityofScience Kagurazaka Three componentMannichreactionwithvariousacceptoraldehydes N methyl 2 pyrrolidinone NMP Three componentMannichreactionwithvariousdonoraldehydes 4 ClaisenCondensation GeneralScheme Mechanism 一种酯的自身缩合 Scopeofapplication 一种含 H的酯与一种不含 H的酯之间的缩合 Examples DirectedClaisencondensation 5 DickmannCondensation Chapter3FormationofCarbon CarbonDouleBonds 1 Eleminationreactions 消去反应 I TheSyntheticMethodsofAlklenes 2 Pyrolyticsyneliminations 顺式热消去反应 Applications Synthesisofterminalalkenesfromprimaryacetates Disadvantages Highreactiontemperature Copereaction Chugavereaction 反应条件比对应的酯热消去温和 3 Wittigandrelatedreactions Wittig及有关反应 WittigReaction G Wittigreceivedthe1979NobelPrizeinChemistryfor manysignificantcontributionstoOrganicChemistry whichincludednotonlytheWittigreaction butalsoPhLipreparedbymetal halogenexchange benzyne andtheWittigrearrangement GeneralScheme Mildreactionconditions Thepositionofthedoublebondisunambiguous Features RepresentativeExamples Example1 Example2 Example3 Example4 Mechanism 2 2 cycloaddition Influenceofsolventontheselectivity ActivityandstereoselectivityofYild Schl ssermodification allowsthepreparationoftransvs cisolefins Schl sserAngew Chem Int Ed Eng 1966 5 126 StabilizedYlides Stabilizedylidesaresolid stabletostorage notparticularlysensitivetomoisture andcanevenbepurifiedbychromatography Becausetheyarestabilized theyaremuchlessreactivethanalkylylides Theyreactwellwithaldehydes butonlyslowlywithketones Thefirststep involvingtheadditiontothealdehyde isslowandreversiblewithstabilizedylides Influenceofsolventontheselectivity Wadsworth Horner EmmonsReaction HornerChem Ber 1958 91 61 1959 92 2499 Wadsworth EmmonsJ Am Chem Soc 1961 83 1733 Reviews Org React 1977 25 73 253 ComprehensiveOrg Syn Vol 1 761 PreparationofPhosphonateEsters ArbuzovJ Russ Phys Chem Soc 1906 38 687 ArbuzovRearragement Thesameapproachtothepreparationof ketophosphonatesisnotsuccessful ButcanusevariationonClaisenconditions ModificationsandScope LiCl tertiaryamines DBU iPr2NEt Et3N Masamune RoushTetrahedronLett 1984 25 2183 Cansubstituteforconventionalconditionsandisespeciallygoodforbasesensitivesubstrates HinderedphosphonatesandhinderedaldehydesincreaseE selectivity trans Still GennarimodificationselectiveforZ alkenes cis AdditionalZ selectivestabilizedphosphonates SelecteddiarylphosphonatesprovideHighZ selectivityaswell PetersonReaction Reviews Org React 1990 38 1 PetersonreactionoffersanalternativetoWittigprocedure TheyaremorereactiveandstericallylessdemandingthanaWittigreagentandthevolatilebyproduct Me3SiOH Me3SiOSiMe3 issimplertoremovethanPh3PO Itdoes however requireasecondsteptopromoteeliminationofthe hydroxysilane Theeliminationisstereospecific acid promotedbeingantiandbase promotedbeingsyn Hudrlik PetersonJ Am Chem Soc 1975 97 1464 StabilizedPetersonReagents ThestabilizedPetersonreagentsgivepredominantlythemoststabletransolefins E Additionalexamples 4 TheTebbeReactionandRelatedTitanium stabilizedMethylenations Tebbe反应及与有关稳定化钛试剂的亚甲基化反应 Toleratesketalandalkenederivatives ScopedefinedbyEvansandGrubbsJ Am Chem Soc 1980 102 3270 ExtendedtotertiaryamidesbyPineJ Org Chem 1985 50 1212 ForananalogoususeofCp2TiMe2 PetasisJ Am Chem Soc 1990 112 6392 5 Sulphoxide sulphenaterearragement Synthesisofallylalcohols 亚砜 次磺酸酯重排 烯丙醇类化合物的合成 Combinedwithalkylationofsulphoxidesthereactionprovidesaversatilesynthesisofdi andtri substitutedallylicalcohols EvansandAndrews Acc Chem Res 1974 7 147 alkylationofallylicalcohlos Example1 Example2 6 Alkenesfromsulphones 由砜制备烯烃 JuliaOlefination Review ComprehensiveOrg Syn Vol 1 792 Example JuliaTetrahedronLett 1973 4833 Juliadevelopedamorerecent single stepvariantthatavoidsthereductiveelimination JuliaBull Soc Chim Fr 1993 130 336 Julia M etal TetrahedronLett 1973 4833Kocienski P J etal J Chem Soc PerkinI 1978 829 Example Ramberg Backlundreaction Org React 1977 25 1 Base SO2 NicolaouK C etal J AmChem Soc 1992 114 7360 BoockmanR K etal J AmChem Soc 1991 113 9682 AlvarzeE etal J AmChem Soc 1995 117 1437 7 Decarboxylationof lactones 内酯的脱羧反应 ReformatskyReaction Note Nostilbenewasformed Synthesisoftri ortetrasubsitutedalkenes Example1 FehrC etal TetrahedronLett 1992 33 2465 MolbierW R etal J Org Chem 1995 60 5378 Example2 Example3 MulzerJ etal J Chem Soc Chem Commun 1979 52 8 Stereoselectivesynthesisoftri andtetra substitutedalkenes 三 四取代烯烃的立体选择性合成 Thefirststepishighlystereoselective TheR4andthelargerofthegroupsR1andR2areantitoeachother EarlyMethod Cornforth J W etal J Chem Soc 1959 112 Development Method1 Corey E J etal J Am Chem Soc 1967 89 4246 Example 54 97 E Method2 Example R Et Yield72 Zweifel G etal J Am Chem Soc 1967 89 2754 Zweifel G etal J Am Chem Soc 1967 89 5085 9 Oxidativedecarboxylationofcarboxylicacids 羧酸的氧化脱羧反应 Sheldon R A etal OrganicReactions 1972 19 279 Jahngen B G E J Org Chem 1974 39 1650 与Dieal Alder反应结合 是制备环状烯烃的好方法 Example1 TanzawaT etal TetrahedronLett 1992 33 6783 Example2 Example3 10 Alkenesfromarylsulphonylhydrazones 由芳基磺酰腙制备烯烃 KolonkoK etal J Org Chem 1978 43 1404 AdlingtonR M etal Acc Chem Res 1983 16 55 Mechanism Lesssubstitutedalkene Example1 Example2 11 FragmentationReactions 裂解反应 X leavinggroup e g OSO2C6H4CH3 p OSO2CH3 100 stereospecific Example 12 OlefinInversionReactions 烯烃构型转换反应 Deoxygenationofepoxides withretentionofgeometry Otherexamples 13 Srereospecificsynthesisofalkenesfrom1 2 diols 由1 2 二醇立体选择性地合成烯烃 Corey WinterOlefinSynthesis CoreyJ Am Chem Soc 1963 85 2677 CoreyJ Am Chem Soc 1965 87 934 EastwoodAust J Chem 1964 17 1392 EastwoodTetrahedronLett 1970 5223 Burgstahler BogerTetrahedron1976 32 309 14 3 3 SigmatropicRearrangements ClaisenandCopeRearrangement Examples EvansJ Am Chem Soc 1975 97 4765 BurgstahlerJ Am Chem Soc 1961 83 198 CarnduffJ Chem Soc Chem Commun 1967 606 Thio ClaisenRearrangement Anadvantageofthethio Claisenrearrangementisthattheprecursorcanbedeprotonatedandalkylated CoreyJ Am Chem Soc 1970 92 5522 YamamotoJ Am Chem Soc 1973 95 2693and4446 BlockJ Am Chem Soc 1985 107 6731 TheCarrollReaction CarrollJ Chem Soc 1940 704 1266 HartungJ Chem Soc 1941 507 CopeJ Am Chem Soc 1943 65 1992 TanabeJ Am Chem Soc 1980 102 862 15 2 3 SigmatropicRearrangements Review ComprehensiveOrg Syn Vol 6 pp834 873 908 Org React 1994 46 105 209 Analogousto 3 3 sigmatropicrearrangementexceptitenlistsalocalizedcharge anion inplaceofadoublebond Examples JuliaTetrahedronLett 1974 2077 LythgoeJ Chem Soc Chem Commun 1972 757 EvansTetrahedronLett 1973 4691 Amino ClaisenRearrangement Thisreactionoccursbestwhennitrogenisconvertedtotheammoniumsalt GilbertTetrahedronLett 1984 25 2303 StilleJ Org Chem 1991 56 5578 NakaiChem Lett 1990 2069 SatoJ Am Chem Soc 1990 112 1999 II OlefinSynthesisExemplifiedwithJuvenileHormone 保幼激素的合成 JuvenileHormone HJ 1 TrostSynthesis J Am Chem Soc 1967 89 5292 2 SyntexSynthesis J Am Chem Soc 1968 90 6224 3 CoreySynthesis J Am Chem Soc 1968 90 5618 4 JohnsonSynthesis J Am Chem Soc 1968 90 6225 5 CoreySynthesis J Am Chem Soc 1970 92 6635 6636 6637 6 JohnsonSynthesis J Am Chem Soc 1970 92 4463 7 Stotter KondoSynthesis J Am Chem Soc 1973 95 4444 J Chem Soc Chem Commun 1972 1311 8 StillSynthesis TetrahedronLett 1979 593 9 OtherSyntheses 1 TrostSynthesis Wadsworth Horner EmmonsReaction Stereoselectivity notmuchdifferencebetweenMeandH secondatomstericeffect bothisomersobtainedfromtheWadsworth Horner Emmonsreaction Modernimprovementsnowavailable RetrosyntheticAnalysis repeatingsubunitsrecognized repeatingreactionsutilized J Am Chem Soc 1967 89 5292 2 SyntexSynthesis J Am Chem Soc 1968 90 6224 RobinsonAnnulationAlkylationDiastereoselectivityDirectedEpoxidationReactionFragmentationReaction SelectiveReduction saturatedvs a b unsaturatedcarbonyl ringstrainassociatedwith5 memberedringcarbonylreleasedonreduction attackfromleasthinderedface THPProtectingGroup ifRgroupcontainschiralcenters diastereomersresult removedbymildacid ThermodynamicEnolate severe1 3 diaxialinteractioninchair likeT S axialalkylation nostericincumberancetoaxialalkylationonleasthinderedfaceoftwistboatT S LiAlH OtBu 3Reduction largereagent usuallyequatorialH delivery 1 2 interaction torsionalstrain relativelyinvarianttoNu size 1 3 stericinteractionhighlydependentonNu size duetoabsenceofaxialC 3 H largereagentnowgivesaxialdelivery Epoxidation inEt2O coordinationofperacidtosolventgivesdeliveryfromtheleasthindereda face inCH2Cl2 H bondingofOHtoperacidprovidesdeliverytothelessaccessibleb face TeranishiJ Am Chem Soc 1979 101 159 FragmentationReaction utilizedtocontrolC Cbondstereochemistry transperiplanarorientationofbreakingbonds dictatesZolefingeometryinproduct 3 CoreySynthesis DissolvingMetalReductionsCyclicPrecursorstoTrisubstitutedOlefinsOxidativeCleavageofEnolEthersLiAlH4ReductionofPropargylAlcoholsCuprateCouplingReactionsAllylicAlcoholOxidation J Am Chem Soc 1968 90 5618 StereospecificSynthesisofTrisubstitutedOlefins MnO2Oxidation mildoxidationofallylicalcohols direct mildmethodforoxidationtoamethylester Epoxidation selective inpolarsolventthemoleculefoldsupsuchthattheterminalC Cismoreaccessible 4 JohnsonSynthesis Trimethylpyridine J Am Chem Soc 1968 90 6225 5 CoreySynthesis J Am Chem Soc 1970 92 6635 6636 1 5 HShift DiimideReduction lesssubstitutedC Creducedmorerapidly generatedin situ 6 JohnsonSynthesis J Am Chem Soc 1970 92 4463 OlefinicKetalClaisenReaction selectivitydependenton1 3 interactioninchair likeT S secondClaisenmoreselectiveduetolargerRgroupvs CO2Me 7 Stotter KondoSynthesis J Am Chem Soc 1973 95 4444 J Chem Soc Chem Commun 1972 1311 8 StillSynthesis TetrahedronLett 1979 593 2 3 SigmatropicRearrangement Chapter4ConversionofFunctionalGroups 1 AdditionofCarbon CarbonDoubleBonds 2 HalogenationofAlcohols GeneralMethods Org Lett 2002 4 4 553 555 TCT DMFMethod Development 2 4 6 trichloro 1 3 5 triazine TCT Table1 ConversionofAliphaticAlcoholsintotheCorrespondingAlkylHalides aForcompleteconversionofthealcohol bThecorrespondingchlorideisformedalso Table2 ConversionofDiolsandUnsaturatedand aminoAlcoholsintotheCorrespondingAlkylHalides aForcompleteconversionofthealcohol bThecorrespondingchlorideisformedalso Mechanism Me3SiCl 该方法对苄醇 伯醇 烯丙醇 叔醇 室温下反应迅速 收率高 J Org Chem 1995 60 2638 3 FormationofAmines GeneralMethods 与氮烯有关的重排反应 Sy