D. A. Evans Pericyclic Reactions: Part-3 Chem 206 Other Reading material http://www.courses.fasharvardedu/-chem206/ [2, 3]Sigmatropic Rearrangements Chemistry 206 Nakai, T Mikami, K. Org. React(NY. 1994, 46, 105-209 Hoffmann, Angew. Chem. Int. Ed 1979, 18, 563-572(Stereochemistry of) Advanced Organic Chemistry Nakai, Chem. Rev. 1986, 86, 885-902 (Wittig Rearrangement) Evans. Accts. Chem. Res 7, 147-55 Sulfoxide Rearrangement Vedejs, Accts. Chem. Res. 1984, 17, 358-364(Sulfur Ylilde Rearrange Lecture Number 13 [3, 3]Sigmatropic Rearrangements Trost, Ed, Comprehensive Organic Synthesis 1992, Vol 5, Pericyclic Reactions-3 Chapter 7.1:( Cope, oxy-Cope, Anionic oxy-Cope Chapter 7. 2, Claisen I Introduction to Sigmatropic Rearrangements S.J. Rhoades, Organic Reactions 1974, 22, 1( Cope, Claisen a 2, 3] Sigmatropic Rearrangements S.R. Wilson, Organic Reactions 1993, 43, 93 (oxy-Cope T.S. Ho, Tandem Organic Reactions 1992, Chapter 12(Cope, Claisen) Paquette, L A (1990) controlled construction of complex cyclic Reading Assignment for week ketones by oxy-Cope gement. Angew. Chem., Int. Ed Engl. 29: 609 Carey Sundberg: Part A; Chapter 11 Concerted Pericyclic Reactions Fleming: Chapter 4 ■ Problems of the Day Thermal Pericyclic reactions Provide a mechanism for this transformation Evans, et al. Acc. Chem. Res. 1974. 7. 149-155 Wednesday Matthew d shair October 16. 2002 For study on this 2, 3 rxn See Baldwin JACS 1971, 93, 6307
http://www.courses.fas.harvard.edu/~chem206/ Me Me S Me Me S PPh3 S=PPh3 Me Me S Me Me D. A. Evans Chem 206 Matthew D. Shair Wednesday, October 16, 2002 ■ Reading Assignment for week: Carey & Sundberg: Part A; Chapter 11 Concerted Pericyclic Reactions Pericyclic Reactions: Part–3 Chemistry 206 Advanced Organic Chemistry Lecture Number 13 Pericyclic Reactions–3 ■ Introduction to Sigmatropic Rearrangements ■ [2,3] Sigmatropic Rearrangements ■ Other Reading Material: Fleming: Chapter 4 Thermal Pericyclic Reactions ■ Problems of the Day: [2,3] Sigmatropic Rearrangements Trost, Ed., Comprehensive Organic Synthesis 1992, Vol 6, Chapter 4.6: Nakai, T.; Mikami, K. Org. React. (N.Y.) 1994, 46, 105-209. Hoffmann, Angew. Chem. Int. Ed. 1979, 18, 563-572 (Stereochemistry of) Nakai, Chem. Rev. 1986, 86, 885-902 (Wittig Rearrangement) Evans, Accts. Chem. Res. 1974, 7, 147-55 (Sulfoxide Rearrangement) Vedejs, Accts. Chem. Res. 1984, 17, 358-364 (Sulfur Ylilde Rearrangements) [3,3] Sigmatropic Rearrangements Trost, Ed., Comprehensive Organic Synthesis 1992, Vol 5, Chapter 7.1: (Cope, oxy-Cope, Anionic oxy-Cope) Chapter 7.2, Claisen S. J. Rhoades, Organic Reactions 1974, 22, 1 (Cope, Claisen) S. R. Wilson, Organic Reactions 1993, 43, 93 (oxy-Cope) T. S. Ho, Tandem Organic Reactions 1992, Chapter 12 (Cope, Claisen) Paquette, L. A. (1990). “Stereocontrolled construction of complex cyclic ketones by oxy-Cope rearrangement.” Angew. Chem., Int. Ed. Engl. 29: 609. For study on this [2,3] rxn See Baldwin JACS 1971, 93, 6307 heat Provide a mechanism for this transformation. Evans, et al. Acc. Chem. Res. 1974, 7, 149-155
D. A. Evans Sigmatropic Rearrangements-1 Chem Sigmatropic rearrangements are those reactions in which a sigma bond[1,3] Sigmatropic Rearrangements(C migration) ( associated substituent) interchanges termini on a conjugated pi system consider the 13-migration of Carbon CH3 [1,3] Sigmatropic rearrangement Consider the orbitals needed to contruct [23]Sg o Construct TS by uniting an allyl and Me radicals Retention at carbon Inversion at carbon [13, 3]Sigmatropic rearrangement bonding bondin bonding [1, 5] Sigmatropic rearrangement Suprafacial on ally l fragment a[1, 3] Sigmatropic Rearrangements(H migration) Sychronous bonding to both termini Sychronous bonding to both termini cannot be achieved from this geometry is possible from this geometry consider the 1, 3-migration of H eochemical constraints on the suprafacial migration of carbon Consider the orbitals needed to contruct with inversion of configuration is highly disfavored on the basis of strain the transition state Ts) [1, 3-Sigmatropic rearrangements are not common a Construct Ts by uniting an ally l and H radical A no observed scrambling of labels X-H HY Y2(ally! HOMO 120°C Suprafacial Geometry Antarafacial Geometry Bridging distance too great for antarafacial migration. These rearrangements are only seen in systems that are highly strained, an attnbute that lowers the activation for rearrangement
X H H C H X R C R H X C Me H 1 3 R X Y:– X R X X H D D D D Y X H H X H Y H X Y X Y D R Y –:X H X X X R X H Y Me H H X H Y D Y CH3 X D D Y X H H Y H3 C X Me H Y CH3 X D D. A. Evans Sigmatropic Rearrangements-1 Chem 206 Bridging distance too great for antarafacial migration. Suprafacial Geometry Antarafacial Geometry bonding Y2 (allyl HOMO) antibonding bonding bonding ■ Construct TS by uniting an allyl and H radical: Consider the orbitals needed to contruct the transition state (TS). ‡ consider the 1,3-migration of H ■ [1,3] Sigmatropic Rearrangements (H migration) [3,3] Sigmatropic rearrangement [2,3] Sigmatropic rearrangement [1,3] Sigmatropic rearrangement [1,5] Sigmatropic rearrangement Sigmatropic rearrangements are those reactions in which a sigma bond (& associated substituent) interchanges termini on a conjugated pi system ■ Examples: Sychronous bonding to both termini is possible from this geometry ❐ The stereochemical constraints on the suprafacial migration of carbon with inversion of configuration is highly disfavored on the basis of strain. bonding bonding Inversion at carbon Suprafacial on allyl fragment Retention at carbon Sychronous bonding to both termini cannot be achieved from this geometry bonding ■ [1,3] Sigmatropic Rearrangements (C migration) consider the 1,3-migration of Carbon ‡ Consider the orbitals needed to contruct the transition state (TS). ❐ Construct TS by uniting an allyl and Me radicals: antibonding Suprafacial on allyl fragment ‡ 1 3 These rearrangements are only seen in systems that are highly strained, an attribute that lowers the activation for rearrangement. 120 °C 3 1 no observed scrambling of labels ✻ ✻ [1,3]-Sigmatropic rearrangements are not common
D. A. Evans Sigmatropic Rearrangements-2 Chem 206 SIGMATROPIC REACTIONS-FMO-Analysis [1, 5] Sigmatropic Rearrangements(C migration) [1s, 5s]alkyl shift RETENTION a[1, 5] Sigmatropic Rearrangements(H migration) [1a, 5a]alkyl shift= INVERSION disfavored 0090 11, 5](C migration): Stereochemical Evaluation RETENTION nonbonding 230280°C 99 I. Ih 15s Dewar-Zimmerman Analysis: Retention 00000 thermal photochemical View as cycloadditon between following species suprafacial preferred 0 phase inversions Huckel toplogy 6 electrons therefore allowed thermally either or the transiton structure
R R R R R H H R R R H H Me Me H H R H H H H R Me Me H H H R H H R H H Me Me D. A. Evans Sigmatropic Rearrangements-2 Chem 206 ■ [1,5] Sigmatropic Rearrangements (C migration) [1s,5s] alkyl shift Þ RETENTION SIGMATROPIC REACTIONS - FMO-Analysis 1 2 3 D/hn R = H, CR3 4 5 1 2 3 4 5 ■ [1,5] Sigmatropic Rearrangements (H migration) [1a,5a] alkyl shift Þ INVERSION disfavored ■ [1,5] (C migration): Stereochemical Evaluation 230-280°C RETENTION [1,5s]H- shift [1,5s]C- shift nonbonding thermal hn photochemical the transiton structure View as cycloadditon between following species: pentadienyl radical + either, or suprafacial preferred Dewar–Zimmerman Analysis: Retention 0 phase inversions Þ Huckel toplogy 6 electrons therefore, allowed thermally 1 3 5 1 5
D. A. Evans Sigmatropic Rearrangements: An Overview Chem 206 [1, 2] Sigmatropic Rearrangements: Carbon The Wittig Rearrangement [1, 2] [2, 3]-Wittig Sigmatropic Rearrangements in Organic Synthesis. " Nakai, [1, 2]sigmatropic rearrangements to cationic centers allowed T: Mikami, K. Chem. Rev. 1986. 86, 885 agner-Meerwein Rearrangemer Marshall, J. A. The Wittig Rearrangement. Trost, B. M. and Fleming, I Ed. Pergamon Press: Oxford, 1991; Vol. 3, pp 975 8-9 BuLi consider as cycloaddition Ea-16 Kcal/ mol FMO anal R This 1, 2-sigmatropic non-concerted R olefin radical cation transition state The Wittig Rearrangement [2, 3] R [ 2]-Sigmatropic rearr to carbanionic centers not observed concerted R FMO analysis consider as cycloaddition FMO analysis ketyl radical 六 olefin radical anion transition state Allyl radical The aagt between concerted and non-concerted pathways can be quite small
● ● ● R R R R R R R R O R C O O R R H BuLi O R Li O Li C O OLi R R H O Li R D. A. Evans Sigmatropic Rearrangements: An Overview Chem 206 [1,2] Sigmatropic Rearrangements: Carbon + + consider as cycloaddition transition state ● ● olefin radical cation ● + [1,2]-Sigmatropic rearrangements to cationic centers allowed. Wagner-Meerwein Rearrangement [1,2]-Sigmatropic rearr to carbanionic centers not observed consider as cycloaddition ●● ●● stepwise ● olefin radical anion ●● ● ●● ● antibonding transition state The Wittig Rearrangement [1,2] "[2,3]-Wittig Sigmatropic Rearrangements in Organic Synthesis.", Nakai, T.; Mikami, K. Chem. Rev. 1986, 86, 885. Marshall, J. A. The Wittig Rearrangement.; Trost, B. M. and Fleming, I., Ed.; Pergamon Press: Oxford, 1991; Vol. 3, pp 975. ● R● This 1,2-sigmatropic rearrangement is non-concerted The Wittig Rearrangement [2,3] Allyl radical ketyl radical ●● ●● Ea ~16 Kcal/mol The G ‡ between concerted and non-concerted pathways can be quite small ●● concerted transition state FMO analysis FMO analysis FMO analysis
D. A. Evans [2, 31-Sigmatropic Rearrangements: An Introduction Chem 206 [2, 3]Sigmatropic Rearrangements The basic process MeMe temp R2 R2 X—Y Rautenstrauch. Chem Commun. 1979.1970-25C-70% X&Y=permutations of C, N,o, s, Se, P; however X is usually a heteroatom X-S, Y=C; Sulfonium Ylide Rearrangement Attributes: Stereoselective olefin construction chirality transfer Representative X-Y Pairs N-o(amine oxides) S-P, S-N, S-o(sulfoxides S-C(sulfur ylids) o-P(phosphites O-C(Wittig rearrangement) N-N, Cr-C (haloium ylids N-c(nitrogen ylid P-C, C-C (homoallylic anions) ythgoe, Chem Commum 1972, 757 S-s(disulfides) ■X·NY=c; Ammonium Ylide Rearrangement An important early paper: Baldwin, J. Chem. Soc., Chem. Comm. 1970, 576 o Sommelet-Hauser: ■ General reviews: Trost, Ed, Comprehensive Organic Synthesis 1992, Vol 6, Chapter 4.6 Nakai, T: Mikami, K Org. React (N.Y. )1994, 46, 105-209 Hoffmann, Angew. Chem. Int Ed. 1979, 18, 563-572 (Stereochemistry of Nakai, Chem. Rev. 1986, 86, 885-902 Wittig Rearrangement Evans, Accts. Chem. Res. 1974, 7, 147-55(sulfoxide Rearrangement) Vedejs, Accts. Chem. Res. 1984. 17, 358-364 (Sulfur Ylilde Rearrangements) IX-0, Y=C; Wittig Rearrangement Review, Pines, Org. Rxns 1970, 18, 416 23] o Modern versions of stevens: R2 Me2N CN Garst, JACS 1976, 98, 1526 Mander JoC 1973. 38. 2915
N Me CN Me R2 R1 R3 – + X Y: R2 R R3 Me O Ph Me Ph O R BuLi BuLi R O Ph Li+ Me Ph O Me Li+ R2 R R3 :X Y Ph O H Li R• Me LiO Ph Me Y :X R R3 R2 Li O R Ph N Me Me Me N R1 R3 R2 Me CN Me O Me Me Me Me S S BuLi BuLi BuLi BuLi N CH2 Me Me O Me Me Me Me S S Li+ CH2 NMe2 H OH Me Me Me Me Me2N R1 R3 R2 CN S S OH Me Me Me Me Me NMe2 important extension lacking CN FG; Sato, JACS 1990, 112, 1999 Mander, JOC 1973, 38, 2915 Buchi, JACS 1974, 96, 7573 + ■ X - N, Y = C; Ammonium Ylide Rearrangement: – ■ X - S, Y = C; Sulfonium Ylide Rearrangement: Lythgoe, Chem Commum 1972, 757 D. A. Evans [2,3]-Sigmatropic Rearrangements: An Introduction Chem 206 – ❐ Sommelet-Hauser: [2,3] ❐ Modern versions of Stevens: Review, Pines, Org. Rxns 1970, 18, 416 [2,3] [2,3] [2,3] Sigmatropic Rearrangements ✻ ✻ ■ General Reviews: ■ Representative X-Y Pairs: ‡ An important early paper: Baldwin, J. Chem. Soc., Chem. Comm. 1970, 576 S–P, S–N, S–O (sulfoxides) O–P (phosphites) N–N, Cl+–C (haloium ylids) P–C, C–C (homoallylic anions). Attributes: Stereoselective olefin construction & chirality transfer ■ The basic process: X & Y = permutations of C, N, O, S, Se, P; however X is usually a heteroatom Trost, Ed., Comprehensive Organic Synthesis 1992, Vol 6, Chapter 4.6: Nakai, T.; Mikami, K. Org. React. (N.Y.) 1994, 46, 105-209. Hoffmann, Angew. Chem. Int. Ed. 1979, 18, 563-572 (Stereochemistry of) Nakai, Chem. Rev. 1986, 86, 885-902 (Wittig Rearrangement) Evans, Accts. Chem. Res. 1974, 7, 147-55 (sulfoxide Rearrangement) Vedejs, Accts. Chem. Res. 1984, 17, 358-364 (Sulfur Ylilde Rearrangements) N–O (amine oxides) S–C (sulfur ylids) O–C (Wittig rearrangement) N–C (nitrogen ylids) S–S (disulfides) Baldwin, JACS 1971, 93, 3556 – ■ X - O, Y = C; Wittig Rearrangement: [2,3] – [1,2] • Garst, JACS 1976, 98, 1526 base temp Rautenstrauch, Chem Commun. 1979, 1970 –25 °C ~70% ~30%