Review Revisiting the Baldwin s Rules Guidelines for Ring Closure Li Yuanhe Anion - 3/4 4/5 5/6 6/7 -trig Supervisors: Prof. Yang Prof. Chen -tet Prof. Tang
Introduction (Sir) Jack Baldwin 1938, Born, London 1960, B. Sc. Imperial College 1964, Ph. D. Imperial College, Prof. Barton 1965, Assistant Lecturer, Imperial College 1967, Assistant Prof., U. Penn. 1970, Assistant Prof., MIT 1972, Full Professor, King's College 1972, Full Professor, MIT 1978, Waynflete Professor, U. Oxford 1997, awarded a knighthood 2005, retirement Rules for ring closure 1976, definitions, basic rules. J. Chem. Soc., Chem. Commun., 1976, 734. (Cited 2393 times, second most cited paper* ) J. Chem. Soc., Chem. Commun., 1976, 736. (5-endo-trig) 1977, rule of enolates J. Chem. Soc., Chem. Commun., 1977, 233. 1982, application to aldol reaction Tetrahedron, 1982, 38, 2939. * Chem. Commun. the most cited paper: Chem. Commun., 1994, 801.; cited 4939 times. Method of gold nanoparticle synthesis. 2/39
Introduction (Sir) Jack Baldwin 1938, Born, London 1960, B. Sc. Imperial College 1964, Ph. D. Imperial College, Prof. Barton 1965, Assistant Lecturer, Imperial College 1967, Assistant Prof., U. Penn. 1970, Assistant Prof., MIT 1972, Full Professor, King's College 1972, Full Professor, MIT 1978, Waynflete Professor, U. Oxford 1997, awarded a knighthood 2005, retirement Rules for ring closure 1976, definitions, basic rules. J. Chem. Soc., Chem. Commun., 1976, 734. (Cited 2393 times, second most cited paper* ) J. Chem. Soc., Chem. Commun., 1976, 736. (5-endo-trig) 1977, rule of enolates J. Chem. Soc., Chem. Commun., 1977, 233. 1982, application to aldol reaction Tetrahedron, 1982, 38, 2939. * Chem. Commun. the most cited paper: Chem. Commun., 1994, 801.; cited 4939 times. Method of gold nanoparticle synthesis. 3/39
The Baldwin s Rules Nomenclature n - endo/exo - tet/trig/dig 3 4 5 6 7 tetrahedron exo- trigonal digonal 3-exo 4-exo tet- 3-endo-tet 4-endo-tet 5-endo-tet 6-endo-tet 7-endo-tet endo- trig- 3-endo-trig 4-endo-trig 5-endo-trig dig- J. Baldwin* Chem. Commun, 1976, 734. R. Moriarty*, J. Org. Chem. 1985, 50, 3710. 4/39
The Baldwin s Rules Nomenclature enolate 3 4 5 6 7 X-endo-trig 3-endo-trig 4-endo-trig 5-endo-trig exo-trig 3~5-enolendo-exo-tet 3~5-enolendo-exo-trig enolendoexo-tet X-exo-trig exo-tet enolexo- exo-trig J. Baldwin* et.al., Chem. Commun., 1977, 233. 5/39
The Baldwin s Rules Baldwin s Explanation To be skipped Limitations (mentioned by Baldwin) Limits to kinetically controlled reaction 3/4 4/5 5/6 6/7 -trig Note: however thermodynamic factor can affect kinetic outcome. Excluded pericyclic reactions Excluded transition metal involvement In ring atoms limited to first row element (C, H, O, N ) Si, P, S : Bond Length; Orbital size; Polarizability; d-orbital H: Bond Length; s orbital; tunneling effect Calculated at B3LYP/ma-def2-SV(P) level All the same in this report if not mentioned 6/39
Anion -, Radical, Cation + Incoming species 7/39
Outline Dig- The major discrepancy Anion, Rad, Cation 3/4 4/5 5/6 6/7 Trig- The 5-endo-trig problem 3/4 4/5 5/6 6/7 -trig Tet endo/exo selectivity 3/4 4/5 5/6 6/7 -tet Enolendo / enolexo- 8/39
The problem Anion, Rad, Cation 3/4 4/5 5/6 6/7 Proposed by Baldwin Orbital and the acute attack angle Free attack transition state: 134 o (Propyne, myself) 132 o (Ethyne, Houk) 9/39
Anion - dig cyclization Anion - 3/4 4/5 5/6 6/7 endo- 4-endo exo- 3-exo By Baldwin 3/4 endo- 4-endo exo- 3-exo 3-exo - vs 4-endo - (3-exo: rare, 4-endo: unprecedented) 3-exo - 4-endo - (by Reaxys general reaction search, rearrangement after 4-endo not included) J. Johnson, et. al., J. Am. Chem. Soc., 2008, 130, 9180. 10/39
4-endo - Some theoretical background Anion - dig cyclization Anion - 3/4 4/5 5/6 6/7 endo- 4-endo exo- 3-exo By Baldwin 3/4 endo- 4-endo exo- 3-exo Marcus theory Remove ΔG factor from ΔG difference NICS (Nuclear independent chemical shift) A measurement of (anti)aromaticity ( 核独立化学位移, in ppm) B 0-4.9 ppm -10.2 ppm > normal H -8.0 ppm 1 2 Obtain Intrinsic (activation) energy ΔE o @ ΔG=0 Thermodynamic induced kinetic preference J. Am. Chem. Soc., 1996, 118, 6317; Chem. Rev., 2005, 105, 3842. 11/39
Anion - dig cyclization Anion - 3/4 4/5 5/6 6/7 endo- 4-endo exo- 3-exo 4-endo - σ-(anti)aromaticity transition state By Baldwin 3/4 endo- 4-endo exo- 3-exo 3-exo σ-2e σ-aromatic 4-endo σ-4e σ-antiaromatic The energy aspect E a : activation energy E r : reaction energy E o : intrinsic energy Alabugin*, Chem. Rev. 2011, 111, 6513 6556 12/39
Anion - dig cyclization Anion - 3/4 4/5 5/6 6/7 endo- 4-endo 5-endo exo- 3-exo 4-exo By Baldwin 4/5 endo- 5-endo exo- 4-exo 4-exo - vs 5-endo - (both rare, endo rarer) Bare cases 4-exo J. Am. Chem. Soc. 1993, 115, 3080. J. Org. Chem. 1993, 58, 6833. Tune by: Aromaticity (thermodynamic induced kinetic preference) J. Org. Chem. 1986, 51, 5040. Chem. Eur. J. 2009, 15, 838.
Anion - dig cyclization Anion - 3/4 4/5 5/6 6/7 endo- 4-endo 5-endo exo- 3-exo 4-exo By Baldwin 4/5 endo- 5-endo exo- 4-exo 4-exo - vs 5-endo - (both rare, endo rarer) Tune by: Bond Polarity MO of difference substrate HOMO α-c 26% β-c 52% LUMO α-c 9.5% β-c 5.1% (mixed with O-H) HOMO α-c 7.1% β-c 0.8% (mixed with O-LP) LOMO α-c 5.6% β-c 27% 14/39
Anion - dig cyclization Anion - 3/4 4/5 5/6 6/7 endo- 4-endo 5-endo exo- 3-exo 4-exo By Baldwin 4/5 endo- 5-endo exo- 4-exo 4-exo - vs 5-endo - (both rare, endo rarer) Tune by: Bond Polarity Chem.Eur. J. 2009, 15, 838. Substrate constrain J. Am. Chem. Soc. 1993, 115, 7023. Tetrahedron Lett. 1986, 27, 5455. 15/39
Anion - dig cyclization Anion - 3/4 4/5 5/6 6/7 endo- 4-endo 5-endo 6-endo exo- 3-exo 4-exo 5-exo By Baldwin 5/6 endo- 6-endo exo- 5-exo 5-exo - vs 6-endo - (both common, exo easier) Energy aspect Default exo Tetrahedron Lett. 1998, 39, 1745. Tetrahedron Lett. 1990, 31, 493. 张力 ensure Myers, et. al., J. Am. Chem. Soc. 2007, 129, 5381. 16/39
Anion - dig cyclization Anion - 3/4 4/5 5/6 6/7 endo- 4-endo 5-endo 6-endo exo- 3-exo 4-exo 5-exo By Baldwin 5/6 endo- 6-endo exo- 5-exo 5-exo - vs 6-endo - (both common, exo easier) Generation of stabilized anion Bond polarity Linker dependent Elimination directed Tetrahedron Lett. 2002, 43, 9187; Heterocycles 2002, 57, 2255. 7-endo & 6-exo not observed in this system 17/39
Anion - dig cyclization Anion - 3/4 4/5 5/6 6/7 By Baldwin 6/7 endo- 7-endo exo- 6-exo 6-exo - vs 7-endo - (6-exo common, (pure) 7-endo rare, Assisted 7-endo common) R. Dillard, N. Easton, J. Org. Chem., 1966, 31, 122.; B. Taylor*, Tetrahedron Lett., 1997, 38, 6467. B. Kundu*, J. Org. Chem. 2011, 76, 6798. 18/39
Anion - dig cyclization Baldwin: Anion, Cation, Rad. 3/4 4/5 5/6 6/7 Search result: Anion - 3/4 4/5 5/6 6/7 19/39
Cation + dig cyclization Cation + 3/4 4/5 5/6 endo- 4-endo 5-endo 6-endo exo- 3-exo 4-exo 5-exo The instability of in-ring vinyl cation HOMO (π) LUMO (LP*) LUMO+1 (π*) HOMO (π) LUMO (LP*) LUMO+1 (π*) 20/39
Cation + dig cyclization Cation + 3/4 4/5 5/6 endo- 4-endo 5-endo 6-endo exo- 3-exo 4-exo 5-exo 4-endo + vs 3-exo + (4-endo very rare (if any), 3-exo unprecedented) Fake 4-endo + : NPEC (Nucleophile-Promoted Electrophilic Cyclization) 5-endo + vs 4-exo + (Both unprecedented) Hanack, M. et. al., Tetrahedron Lett. 1968, 44, 4613. Hanack, M. et. al., Angew. Chem., Int. Ed. 1978, 17, 333. 21/39
Cation + dig cyclization Cation + 3/4 4/5 5/6 endo- 4-endo 5-endo 6-endo exo- 3-exo 4-exo 5-exo 6-endo + vs 5-exo + (Both very common, subtle control) J. Org. Chem. 1992, 57, 883. J. Am. Chem. Soc. 1969, 90, 4521. Chem. Commun. 1990, 310. 22/39
Outline Dig- The major discrepancy Anion - 3/4 4/5 5/6 6/7 Trig- The 5-endo-trig problem 3/4 4/5 5/6 6/7 -trig Tet endo/exo selectivity 3/4 4/5 5/6 6/7 -tet Enolendo / enolexo- 23/39
Anion - Trig= cyclization 3/4 4/5 5/6 6/7 -trig Anion-trig attack The endo difficulty Planer: No orbital overlap Stereoelectronic required distortsion HOMO-LUMO orbital recombination ( overlap ): 24/39
Anion - Trig= cyclization 3/4 4/5 5/6 6/7 -trig By Baldwin 3/4 endo- 4-endo -trig exo- 3-exo 3-exo-trig - vs 4-endo-trig - (Both unprecedented) Only indirect 4-endo-trig reported 4-exo ~ 7-exo common G. Rousseau*, J. Org. Chem. 1999, 64, 81-85 25/39
Anion - Trig= cyclization 3/4 4/5 5/6 6/7 -trig 5-endo-trig Anion stabilization at attacked endo position Oxonium / iminium J. Am. Chem. Soc, 1995, 117, 6394 Tetrahedron Lett.,1985, 26, 4455. J. Am. Chem. Soc,, 2005, 127, 11505. J. Org. Chem., 1990, 55, 4801. 26/39
Outline Dig- The major discrepancy Anion - 3/4 4/5 5/6 6/7 Trig- The 5-endo-trig problem 3/4 4/5 5/6 6/7 -trig Tet endo/exo selectivity 3/4 4/5 5/6 6/7 -tet Enolendo / enolexo- 27/39
Anion - tet cyclization 3/4 4/5 5/6 6/7 -tet By Baldwin 3/4 6/7 endo- 4-endo 7-endo -tet exo- 3-exo 6-exo endo-tet vs exo-tet (-exo always win) Misuse of nomenclature X-endo-tet for epoxide endo-tet is not a cyclization process only for completeness Baldwin 28/39
Anion - tet cyclization Misuse of nomenclature X-endo-tet for epoxide Countless (important) papers misuse the endo-tet (said Chem. Commun., 2013, 49, 11246) Kinya Hotta*, Xi Chen*, et. al., Nature, 2012, 483, 355. 29/39
Anion - tet cyclization Misuse of nomenclature X-endo-tet for epoxide Countless (important) papers misuse the endo-tet Nature doesn t work against stereoelectronic principles; Nature chooses by giving an additional advantage to one of the two favorable processes. Chem. Commun., 2013, 49, 11246. Kinya Hotta*, Xi Chen*, et. al., Nature, 2012, 483, 355. 30/39
Anion - tet cyclization 3/4 4/5 5/6 6/7 -tet Small-ring endo-tet almost always impossible Eschenmoser, et. al., Helvetica Chimica Acta, 1970, 53, 2059 31/39
Anion - tet cyclization 3/4 4/5 5/6 6/7 -tet Small-ring endo-tet almost always impossible By Baldwin 3/4 6/7 -tet endo- 4-endo 7-endo exo- 3-exo 6-exo orbital of 6-exo-tet TS Is the mechanism of S N 2 reaction really that simple? Direct S N 2 mechanisms By crossed molecular beam exp. & quantum dynamic calculation Jing Xie, William L. Hase, Science, 2016, 352, 32. 32/39
Anion - tet cyclization 3/4 4/5 5/6 6/7 -tet By Baldwin 3/4 6/7 endo- 4-endo 7-endo -tet exo- 3-exo 6-exo Is the mechanism of S N 2 reaction really that simple? Other indirect S N 2 pathway Jing Xie, William L. Hase, Science, 2016, 352, 32. 33/39
Anion - tet cyclization 3/4 4/5 5/6 6/7 -tet Endo/exo selectivity of exo-tet reaction (default exo, endo tunable) Stabilized partial charge Nicolaou, et.al., Chem. Commun., 1985, 1359.; J. Am. Chem. Soc., 1989, 111, 5335. 34/39
Anion - tet cyclization Endo/exo selectivity of exo-tet reaction (default exo, endo tunable) Destabilized partial positive charge Reagent controlled Chem. Eur. J.; 1997, 3, 849. Derived from other species Angew. Chem. Int. Ed. 2006, 45, 810. J. Org. Chem., 2013, 78, 872. Tetrahedron Lett., 1994, 35, 2179 35/39
Outline Dig- The major discrepancy Anion - 3/4 4/5 5/6 6/7 Trig- The 5-endo-trig problem 3/4 4/5 5/6 6/7 -trig Tet endo/exo selectivity 3/4 4/5 5/6 6/7 -tet Enolendo / enolexo- 36/39
Enolendo- / enolexo- 3 4 5 6 exo- enolendo- 3-enolendo -exo-tet/trig 4-enolendo -exo-tet/trig 5-enolendo -exo-tet/trig 6-enolendo -exo-tet/trig exo- enolexo- 3-enolexo -exo-tet/trig 4-enolexo -exo-tet/trig 5-enolexo -exo-tet/trig 6-enolexo -exo-tet/trig 3-enolendo Mechanism of Favorskii Rearrangement 5/6-enolendo Not applicable on oxonium / iminium Loose molecular orbital (?!) J. Am. Chem. Soc,, 2005, 127, 11505. 37/39
Summary Anion - 3/4 4/5 5/6 6/7 Cation + 3/4 4/5 5/6 endo- 4-endo 5-endo 6-endo exo- 3-exo 4-exo 5-exo Anion - 3/4 4/5 5/6 6/7 -trig Cation + 3/4 4/5 5/6 endo- 4-endo 5-endo 6-endo -trig exo- 3-exo 4-exo 5-exo Anion - 3/4 4/5 5/6 6/7 -tet Cation + 3/4 4/5 5/6 endo- 4-endo 5-endo 6-endo -tet exo- 3-exo 4-exo 5-exo 3 4 5 6 exo- enolendo- 3-enolendo -exo-tet/trig 4-enolendo -exo-tet/trig 5-enolendo -exo-tet/trig 6-enolendo -exo-tet/trig exo- enolexo- 3-enolexo -exo-tet/trig 4-enolexo -exo-tet/trig 5-enolexo -exo-tet/trig 6-enolexo -exo-tet/trig Radical: 3,4-endo/exo-trig/dig: rare; 5,6-trig/dig: favor exo 38/39
Recommended Reviews (not in order) Alabugin*, et. al., Chem. Commun., 2013, 49, 11246. Zeni*, et. al., Chem. Rev. 2011, 111, 2937 2980 Alabugin*, Chem. Rev. 2011, 111, 6513 6556 Sarah Wengryniuk, Breaking the Rules: "Anti-Baldwin" Cyclizations, Baran Group Meeting Alabugin*, et. al., J. Am. Chem. Soc. 2011, 133, 12608 12623 X Jiang and H Liu, 4.07: Electrophilic Cyclization, Comprehensive Organic Synthesis II, Volume 4 Radical(not covered): The book, Chapter 11, Free Radical Reactions Hideo Togo, Advanced Free Radical Reactions for Organic Synthesis Dowd*, et. al., Chem. Rev. 1993, 93, 2091. Uta Wille*, Chem. Rev. 2013, 113, 813 853 39/39
Acknowledgements Prof. Yang, Prof. Chen, Prof. Tang Mr. Liu Dong-Dong B630 Everyone in Lab. and everyone here Ac 40/39