ecent Development in Tandem adical eactions (T) Feng u Jan. 13, 2006 Contents Brief Introduction of the istory of T Definition of T Intramolecular T Intermolecular T T as Key Steps in Total Synthesis of atural Products Summary and utlook
Contents Brief Introduction of the istory of T Definition of T Intramolecular T Intermolecular T T as Key Steps in Total Synthesis of atural Products Summary and utlook Brief Introduction of the istory of T Moses Gomberg In 1900 Triphenylmethyl radical In 1964 Marc Julia ideo Togo An example of intermolecular T In 1988 An early example of T In 1995 ed A. Porter ang Dan The first example of enatioselective intramolecular T In 2002 The first example of enatioselective intermolecular T
The Founding of Triphenylmethyl adical In 1900 C Cl Zn C In 1901 In 1907 C Cl C Moses Gomberg (1866-1947) Gomberg narrowly missed the award of the obel prize for his discovery. Thomas T. Tidwell M. Gomberg J. Am. Chem. Soc. 1900, 22, 757. An Early Example of T (C 2 ) 2 C C 2 Et C 6 12,eat C C 2 Et (C 2 ) 2 eat C C 2 Et C C 2 Et C C 2 Et Mark Julia; et al. Bull. Soc. Chim. Fr. 1964, 1122. Mark Julia; et al. Acc. Chem. es. 1971, 4, 386.
Contents Brief Introduction of the istory of T Definition of T Intramolecular T Intermolecular T T as Key Steps in Total Synthesis of atural Products Summary and utlook Definition of T Definition of T : Chemical processes in which two or more consecutive molecular transformations are intimately linked together in time and space, (that is, in one pot ), have been variously dubbed cascade, domino, tandem, or sequential reactions. consecutive molecular transformations : should be radical process In classifying free-radical cascades only the propagation steps which form the cycle will be considered as strict integral parts of the cascade. The initiation and termination steps do not form part of the central chain process. John C. Walton; et al. Angew. Chem. Int. Ed. 2001, 40, 2224
Contents Brief Introduction of the istory of T Definition of T Intramolecular T Intermolecular T T as Key Steps in Total Synthesis of atural Products Summary and utlook Intramolecular T Classes of Intramolecular Free-radical eactions Baldwin s ules General Strategies for Intramolecular T a) ne ing Template strategy b) Acyclic Strategy c) Transannular Strategy Enatioselective Intramolecular T
Classes of Intramolecular Free-radical eactions n n C (Cyclization) =C 2, 2,; =C 2,, Z Z S (Substitution) Z =, S, Se, Te (ydrogen abstraction) na 1 2 1 2 An M (Migration) F (Fragmentation) na na F 2 (Fragmentation) John C. Walton; et al. Angew. Chem. Int. Ed. 2001, 40, 2224 Baldwin s ules ing number Tet E Trig Dig ED Tet Trig Dig 3 4 5 Sir Jack Baldwin 6 7 David A. Evans; et al. Advanced rganic Chemistry, fall term, 2004
ne ing Template Strategy for Intramolecular T Dennis P. Curran irsutene Br TP I Bu 3 Sn C 5 C 5 Bu 3 Sn TM Dennis P. Curran; et al. J. Am. Chem. Soc. 1985, 107, 1448. Dennis P. Curran; et al. Tetrahedron 1985, 41(19), 3943. ne ing Template Strategy for Intramolecular T Et Et 1) LDA/MeI MgBr Bu 3 Sn 2) LDA Br Br Br Br C 5 C 5 Silphiperfol-6-ene Dennis P. Curran; et al. J. Am. Chem. Soc. 1986, 108, 1122.
Acyclic Strategy for Intramolecular T (C 2 ) 2 C C 2 Et C 6 12,eat C C 2 Et (C 2 ) 2 eat C 6n C 6n C C 2 Et C C 2 Et C C 2 Et Mark Julia; et al. Bull. Soc. Chim. Fr. 1964, 1122. Mark Julia; et al. Acc. Chem. es. 1971, 4, 386. Acyclic Strategy for Intramolecular T Br P 3 Bu 3 Ge Benzene C 5 C 5 C 5 Bu 3 Ge Benzene Mixture of isomers Athelstan L. J. Beckwith; et al. Tetrahedron Lett. 1985, 26, 3349.
Acyclic Strategy for Intramolecular T Mn(Ac) 3,Cu(Ac) 2 C 2 Me Ar, rt, 20 h C 6n C 6n C 2 Me Me 2 C Me 2 C C 6n C 6x Me 2 C Me 2 C Me 2 C illip A. Zoretic; et al. Tetrahedron Lett. 1991, 32, 4819. Transannular Strategy Si Me Br 1) 3 Sn, AIB, Benzene, eat 2) KC 3,KF, 2 2,Me,TF Me Max Malacria Si Si Si Si C 5x C 5x C 5n Me Me Me Me Max Malacria; et al. Angew. Chem. Int. Ed. 2002, 41, 3284.
Enatioselective Intramolecular T Et Br Mg(Cl 4 ) 2, toluene C 2 Et C 3 BEt 3, 2-20 o C Br Et C 6n Et C 6x Et ang Dan Mg(Cl 4 ) 2 :1.0eqligand:1.1eq 84% ee Dan ang; et al. Angew. Chem. Int. Ed. 2002, 41, 3014. Enatioselective Intramolecular T Et Br b(tf) 3,C 2 Cl 2 BEt 3, 2-78 o C Br C 2 Et C 3 66% ee b(tf) 3 :1.0eq ligand : 1.1 eq substrate e-face C 6n ring-flip C 5x Dan ang; et al. Angew. Chem. Int. Ed. 2002, 41, 3014.
Enatioselective Intramolecular T Et Se Mg(Cl 4 ) 2, toluene C 2 Et C 3 BEt 3, 2-20 o C Se Mg(Cl 4 ) 2 : 1.0 eq ligand : 1.1eq Mg(Cl 4 ) 2 : 0.3 eq ligand : 0.33eq 97% ee 87% ee Catalytic Se Me Mg(Cl 4 ) 2, toluene BEt 3, 2-20 o C C 2 Me 91% ee Se Dan ang; et al. Angew. Chem. Int. Ed. 2006, 45, 255. Contents Brief Introduction of the istory of T Definition of T Intramolecular T Intermolecular T T as Key Steps in Total Synthesis of atural Products Summary and utlook
Intermolecular T Classes of Intermolecular Free-radical eactions Classes of adical Acceptor/ adical Precursor General Strategies for Interamolecular T a) Linear Addition Strategy b) Addition-Annulation Strategy Enatioselective Intermolecular T Classes of Intermolecular Free-radical eactions A (Addition) Z Z S (Substitution) (ydrogen abstraction)
Classes of adical Acceptor/ adical Precursor radical precursor radical acceptor Vicinal radical precusor/radical acceptor C C C C C Geminal radical precusor/radical acceptor C S 2 C IIhyong yu and Dennis P. Curran; et al. Chem. ev. 1996, 96, 177. Linear Addition Strategy w Z Z Bu 3 Sn Bu 3 Sn Bu 3 Sn Z Z and w : alogens : and Z: Electron-withdrawing Groups ideo Togo; et al. Tetrahedron Lett. 1988, 29, 4133.
Linear Addition Strategy I C C ' AIB, C 6 6,90 0 C 2~30atm,12h ' Bu 3 SnI I Bu 3 Sn IIhyong yu ' ' ' IIhyong yu; et al. J. Am. Chem. Soc. 1991, 113, 8558. Linear Addition Strategy C 1 AIB, C 6 6,90 0 C 1 80 atm, 8h 1 Bu 3 Sn Bu 3 Sn 1 C 1 IIhyong yu; et al. J. Am. Chem. Soc. 1993, 115, 1187.
Linear Addition Strategy Mg 2 (air) 2 2 Mg Mg irokazu Urabe; et al. J. Am. Chem. Soc. 2005, 127, 18006 Addition-Annulation Intermolecular T I I 1 E sunlamp, C 6 6 Bu 3 Sn 70 ~ 80 0 C E 1 I E 1 E 1 1 E C 5 E 1 E 1 C 6n E 1 Dennis P. Curran; et al. J. Am. Chem. Soc. 1986, 108, 1122.
Addition-Annulation Intermolecular T 2 1 3 C AIB, C 6 6 80 0 C,2~3 h 2 1 3 75 ~ 90 atm 1 3 2 C 2 1 3 C 5 2 1 3 IIhyong yu; et al. J. Chem. Soc. Chem. Commun. 1991, 1018. Addition-Annulation Intermolecular T I C AIB, C 6 6 90 atm, 3~4 h 70 ~80 0 C a b C C 5 C C 5n Bu 3 Sn Bu 3 Ge ield (%) a 44 6 ield (%) b 0 27 IIhyong yu; et al. J. Am. Chem. Soc. 1996, 118, 10670.
Addition-Annulation Intermolecular T I C C AIB, C 6 6,80 0 C 80 atm, 3h C C C C 5 C C C IIhyong yu and Dennis P. Curran; et al. Chem. ev. 1996, 96, 177. Addition-Annulation Intermolecular T C Bu 3 Sn AIB, C 6 6 90 atm, 80 0 C, 2 h C Bu 3 Sn AIB, C 6 6 83 atm, 90 0 C, 8 h Bu 3 Sn Bu 3 Sn AIB, C 6 6 C Bu 3 Sn 83 atm, 90 0 C, 8 h IIhyong yu; et al. J. Am. Chem. Soc. 1998, 120, 5838. IIhyong yu; et al. J. Am. Chem. Soc. 2003, 125, 5632.
Addition-Annulation Intermolecular T - I C Me 3 SnSnMe 3 150 0 C, 2 h Me 3 SnSnMe 3 light Me 3 Sn 3 C C C 5 C 6 Dennis P. Curran; et al. J. Am. Chem. Soc. 1991, 113, 2127. Addition-Annulation Intermolecular T S S 2 SS C 2 Cl 2 light, 2 h S S SS light S S S S S S S 2 S S 2 S S ebecca Braslau; et al. J. rg. Chem. 2005, 70, 10854.
Enatioselective Intermolecular T I Zn(Tf) 2,C 2 Cl 2 BEt 3, 2-78 o C BEt 3, 2 I Zn(Tf) 2 1 eq =, 90% ee ed A. Porter; et al. J. Am. Chem. Soc. 1995, 117, 11029. Enatioselective Intermolecular T Model for allylation ed A. Porter ed A. Porter; et al. J. Am. Chem. Soc. 1995, 117, 11029.
Enatioselective Intermolecular T S Ar I Sn 1 2 3 Zn(Tf) 2,C 2 Cl 2 S Ar BEt 3, 2-78 o C BEt 3, 2 I S Ar Sn 1 2 3 1 2 Sn 3 S Ar Zn(Tf) 2 1 eq Ar : Tin reagent : Allyl 2 Bu 2 Sn 84% ee Takeshi Toru; et al. Tetrahedron Lett. 2001, 42, 2981. Enatioselective Intermolecular T Model for allylation Takeshi Toru Takeshi Toru; et al. Tetrahedron Lett. 2001, 42, 2981.
Enatioselective Intermolecular T I Sn( 2 ) 3 Lewis acid, C 2 Cl 2 BEt 3, 2-78 o C BEt 3, 2 I Sn( 2 ) 3 Sn( 2 ) 3 MgI 2 (0.3eq) Allyltributyltin 97%ee dr 99 : 1 Cu(Tf) 2 (0.3eq) Allyltriphenyltin -96%ee dr 99 : 1 Mukund P. Sibi; et al. J. Am. Chem. Soc. 2001, 123, 9472. Enatioselective Intermolecular T Model for first-step attack Mukund P. Sibi Mukund P. Sibi; et al. J. Am. Chem. Soc. 2001, 123, 9472.
Contents Brief Introduction of the istory of T Definition of T Intramolecular T Intermolecular T T as Key Steps in Total Synthesis of atural Products Summary and utlook T as Key Steps in Total Synthesis of atural Products Intramolecular T as Key Steps in Total Synthesis of atural Products Intermolecular T as Key Steps in Total Synthesis of atural Products
Intramolecular T as Key Steps C 2 Me C 2 Me 3 C C 2 S Bu 3 Sn AIB, 80 o C F 4 Lubiminol C 2 Me C 3 C 2 Me F 3 C 2 Me Bu 3 Sn C 2 Me TM Michael T. Crimmins; et al. J. Am. Chem. Soc. 1998, 120, 1747. Intramolecular T as Key Steps Paniculatine I SiMe 2 SiMe 2 TMS Bu 3 Sn AIB SiMe 2 SiMe 2 TMS C 5 TMS C 5 TMS TM Chin-Kang Sha; et al. J. Am. Chem. Soc. 1999, 121, 9875.
Intermolecular T as Key Steps Br Me 3 SnSnMe 3 light Me 3 Sn C camptothecin C 5 C 6 TM Dennis P. Curran; et al. Angew. Chem. Int. Ed. 1995, 34, 2683. Intermolecular T as Key Steps C 2 tbu Me 2 C C 2 Me Me 2 C C 2 Me Matrine Et S S benzene lauroyl peroxide EtCSS C 2 tbu Me 2 C C 2 Me Me 2 C C 2 Me Me 2 C C 2 Me lauroyl peroxide benzene C 2 tbu C6 C 2 tbu C6 C 2 tbu TM Samir Z. Zard; et al. Angew. Chem. Int. Ed. 1998, 37, 1128.
Contents Brief Introduction of the istory of T Definition of T Intramolecular T Intermolecular T T as Key Steps in Total Synthesis of atural Products Summary and utlook Summary and utlook Upon reflection, one realizes that the initial misconception about radicals as highly reactive short-lived species that are difficult to tame hindered their use,especially in stereoselective reactions. Mukund P. Sibi; et al. Chem. ev. 2003, 103, 3263. Synthetic efficiency ne pot Tandem adical eactions Atom economical Environmental benign John C. Walton; et al. Angew. Chem. Int. Ed. 2001, 40, 2224.
Summary and utlook adical Precursor initiation adical-1 Propagation adical-2 Termination eutral Species Atom Transfer 10 4 ~10 8 dm 3 mol -1 s -1 The Fate of adicals Addition to neutral Molecule 10 4 ~10 8 dm 3 mol -1 s -1 Fragmentation 10 5 ~10 9 s -1 Coupling 10 9 dm 3 mol -1 s -1 Mukund P. Sibi; et al. Chem. ev. 2003, 103, 3263. Future Development of T Acknolegement Prof. Jianbo Wang Associate Prof. Zhangjie Shi and Zhixiang u Members in ur Group All Members in the Institute of rganic Chemistry
狗年吉祥