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%
D A. Evans [2,31-Sigmatropic Rearrangements: Introduction-2 Chem 206 IX-O, Y=C; Wittig-like Rearrangements IX-S,Y=O; Sulfoxide Rearrangement R R OMe Buchi JAcs 1974. 96. 5563 Accts. Chem. Res. 1974. 7. 147 IX-Se, Y= N; Related Rearrangement n thinking about this rearrangement, also consider the carbenoid res R2 IX-O,Y= C; An all-carbon Rearrangement NH-Ts Se Ts R2 ns. Tet Let. 198 R okins JOC 1984 Hopkins, JOC 1985, IX-S,Y=N; Related Rearrangement note that the product contains the retrons TS-N-Cl Smith, Chem. Commun. 1974, 695: Smith, JOC 1977, 42, 3165 ■X·N,Y=o; Meisenheimer Rearrangement R2 LR3Zn/HOAc R2 85% yield overall Dolle. Tet let 1989. 30. 4723 Tanabe. Tet Let. 1975. 3005
N Me Me O R2 R1 R3 + – R2 R1 R3 OH R1 R3 R2 N N O H OMe OMe NMe2 –N2 Cu(I) C NMe2 O R2 R1 R3 O R1 R3 R2 C NMe2 O H R2 R1 R3 C O R1 R3 R2 O R2 R1 R3 NMe2 R2 R1 R3 OR O ROH R2 R1 R3 Se Ar N Ts S Ar O R1 R3 R2 S TsO Ph Ts–N–Cl Na+ Se Ar N R2 R1 R3 Ts R1 R3 R2 O S Ar S Ph TsO N Ts BuLi PhSCl R1 R3 R2 O N Me Me N Ts R1 R3 R2 OH N TsO Ts SPh N Ts TsO R2 R1 R3 OH NH–Ts R1 R3 R2 (MeO)3P NaOH keq < 1 note that the product contains the retrons for the enolate Claisen rearrangement Smith, Chem. Commun. 1974, 695; Smith, JOC 1977, 42, 3165 ■ X - O, Y = C; An all-carbon Rearrangement : D. A. Evans [2,3]-Sigmatropic Rearrangements: Introduction-2 Chem 206 In thinking about this rearrangement, also consider the carbenoid resonance form as well : – + 140 °C ■ X - O, Y = C; Wittig-like Rearrangements Buchi, JACS 1974, 96, 5563 – Hopkins, Tet Let. 1984, 25, 15 Hopkins, JOC 1984, 49, 3647 ✻ ✻ ■ X - S, Y = N; Related Rearrangement + ✻ selenophile Evans, Accts. Chem. Res. 1974, 7, 147 ✻ thiophile – + ■ X - S, Y = O; Sulfoxide Rearrangement ✻ ✻ Hopkins, JOC 1985, 50, 417 ■ X - N, Y = O; Meisenheimer Rearrangement Zn/HOAc Tanabe, Tet Let. 1975, 3005 ■ X - Se, Y = N; Related Rearrangement – [2,3] 85% yield overall – Dolle, Tet Let. 1989, 30, 4723
D. A. Evans [2, 31-Sigmatropic Rearrangements: Olefin Geometry Chem 206 1, 2-Disubstitution: Good Trans Olefin Selectivity Starting olefin: Trans 75to-50° (E)selectivity: only isomer" Rb CO2H Nakai. Tet. Lett 1981. 22. 69 disfavored R R2(MeO)3P RiNe Ra& rb prefer to orient in pseudo-equatorial positions during rearrangement; RUI Rl-X nevertheless, this is a delicately balanced situation Evans. Accts. Chem. Res. 1974.7. 147-55 Starting olefin: Cis The preceeding transition state models do not explain some of the results u Cis selectivity has been observed: Still JACS 1978, 100, 192 L Rb rato,65:35 J However, Cis selectivity is dependent on starting olefin geometry Conclusions OH only(E)isomer(91%) J Olefin geometry dictates sense of asymmetric induction in rearrangement J( z) Olefin rearrangements might exhibit higher levels of 1, 3 induction J Product olefin geometry can be either(E)or(2)from(E)starting material Several theoretical studies have been published: Good reading J Product olefin geometry will be(E) from 2) starting materia Houk JOC 1991, 56, 5657 (Sulfur ylide transition states) Houk JOC 1990, 55, 1421(Wittig transition states)
Me O Ph RLi Y :X Ra Rb X Y: Ra Rb X Y Rb H H Ra H X Y H Rb Ra Rb Ra :X Y Ra Y X H H Rb Y :X Ra Rb H Ra Rb X Y H X Ra Rb Y: Ra Rb :X Y CO2H O Me R1 S Ar O R2 R2 S Ar O R Me O SnBu3 R Bu3Sn O Me RLi R1–X n-BuLi n-BuLi O S R1 Ar R2 HO Me Ph CO2H Me HO R Me OH Me OH R MeOH (MeO)3P R1 R2 OH R OH Me ❏ Product olefin geometry will be (E) from (Z) starting material Houk JOC 1990, 55, 1421 (Wittig transition states) Houk JOC 1991, 56, 5657 (Sulfur ylide transition states) Several theoretical studies have been published: Good reading only (E) isomer (91%) -78 °C ❏ However, Cis selectivity is dependent on starting olefin geometry -78 °C ratio, 65:35 The preceeding transition state models do not explain some of the results: Evans, Accts. Chem. Res. 1974, 7, 147-55 (E) selectivity: >95% Nakai, Tet. Lett 1981, 22, 69 (E) selectivity: 75% 2 LDA -75 to -50 °C -75 to -50 °C (E) selectivity: "only isomer" ❏ Product olefin geometry can be either (E) or (Z) from (E) starting material ❏ (Z) Olefin rearrangements might exhibit higher levels of 1,3 induction ❏ Olefin geometry dictates sense of asymmetric induction in rearrangement Conclusions ‡ favored ‡ highly disfavored ❏ Cis selectivity has been observed: Still JACS 1978, 100, 1927. Starting olefin: Trans Ra & Rb prefer to orient in pseudo-equatorial positions during rearrangement; nevertheless, this is a delicately balanced situation ‡ ‡ D. A. Evans [2,3]-Sigmatropic Rearrangements: Olefin Geometry Chem 206 ■ 1,2-Disubstitution: Good Trans Olefin Selectivity Starting olefin: Cis favored disfavored
D. A. Evans [2,31-Sigmatropic Rearrangements: Olefin Geometry Chem 206 a Starting olefin:(E)Trisubstituted a(Z selectivity has been observed: Still JACS 1978, 100, 1927 (E)-path 95%,>96%(2 Me-78°c ()-path halogen Still says that the TS is early, so that the 1, 2 interactions in the TS are most Rr-Me interaction can destabilize the()transition state while(4 Ts might be destabilized by R, interactions with both X-y and allyl moiety C,Ho. M ■ Starting olefin:(2) CH favored CH2-Li C491 ()-path disfavored R2 a() selectivity has also been observed by others: Sato JACS 1990, 112, 1999 Conclusions 76%区z)(E955 J Olefin geometry dictates sense of asymmetric induction in rearrangement u(4 olefin rearrangements might exhibit higher levels of 1, 3 induction NMe2 J Product olefin geometry can be either(E)or(Z) from(E)starting material Cs-F in HMPA u Product olefin geometry will be(E)from(2) starting material Mei chams 61%(E)(2)1000
N + Me Me Me Me N + Me Me CH2–TMS Me X R1 R2 Y: Me X Y: R1 R2 Me X Y R2 H H R1 Me R1 Y X H H R2 Me H R1 R2 X Y H Me H X Y H R2 R1 Me Y :X R1 R2 Me R1 R2 :X Y Me R2 R1 :X Y Me Y :X R1 R2 Me Me O n-Bu CH2–Li O SnBu3 Me n-Bu n-Bu Me O Li n-BuLi KH H Me O H2C H H Li C4H9 Me H C4H9 H O H2C H Li n-Bu Me OH n-Bu Me OH Me NMe2 Me NMe2 halogen SnBu3 Me n-Bu LiO CH2 Me CH2 LiO R1 ❏ Olefin geometry dictates sense of asymmetric induction in rearrangement ❏ (Z) Olefin rearrangements might exhibit higher levels of 1,3 induction ❏ Product olefin geometry can be either (E) or (Z) from (E) starting material ❏ Product olefin geometry will be (E) from (Z) starting material ■ Starting olefin: (Z) D. A. Evans [2,3]-Sigmatropic Rearrangements: Olefin Geometry Chem 206 ‡ ‡ R1–Me interaction can destabilize the (E) transition state while (Z) TS might be destabilized by R1 interactions with both X-Y and allyl moiety. ■ Starting olefin: (E) Trisubstituted highly disfavored ‡ favored ‡ Conclusions (E)-path (Z)-path -78 °C ■ (Z) selectivity has been observed: Still JACS 1978, 100, 1927. 95%, >96% (Z) Still says that the TS is early, so that the 1,2 interactions in the TS are most important. (Z)-path (E)-path ‡ ‡ destabilizing ■ (Z) selectivity has also been observed by others: Sato JACS 1990, 112, 1999. -70 °C LHMDS, NH3 76%, (Z):(E) 95:5 X - X - 61%, (E):(Z) 100:0 Cs–F in HMPA 25 °C
D A. Evans [2, 3-Sigmatropic Rearrangements: Olefin Geometi Chem 206 Trisubstituted olefins via [2, 3]-rearrangement of sulfoxides a Trisubstituted olefins via [2, 3]-rearrangement of sulfonium ylides Cuso R1 Grieco,JOc1973,38,2572 ((z>90:10(70 (Z)-path I procedure for the direct synthesis of sulfur ylides R pKa- 18(DMSO a=90:10(95%) a Trisubstituted olefins via Wittig [2, 3]-rearrangement Accts. Chem. Res. 1974, 7, 147-55 C5H11 IO CO2H Nakai. Tet Let 1981, 22, 69 NH MeoH However, this reaction is not general (E(z)>973(80-85% 25°cMe (B区z)3169 equivalent to: () HO CO2 Me H OH
Me N S N Me S O R1 Me Ar n-BuLi N Me N S Me Li H PhS O H H R1 Me H R1 O S H H Me Ph Br Me Me OH Me Me Me N Me N S Me Me H OH Me N S N Me Me Me O Me Me N Me N S Me O S R1 Me Ph RCO3H R1 S O Me Ph Bu S Ph Me Me O C5H11 CO2H CO2Me Me O Me N2 C(COOMe)2 S R R CuSO4 :CR2 Me S Ph Bu CO2Me CO2Me C5H11 HO CO2H Me S R R C R R Me HO CO2Me Me C R R S R R H Me S Bu Ph CO2Me CO2Me Trisubstituted olefins via [2,3]-rearrangement of sulfoxides: However, this reaction is not general: LDA (E):(Z) 31:69 Nakai, Tet Let 1986, 27, 4511 Nakai, Tet Let 1981, 22, 69 (E):(Z) > 95:5 (74%) 2 LDA ■ Trisubstituted olefins via Wittig [2,3]-rearrangement: pKa ~ 18 (DMSO base + + – + A general procedure for the direct synthesis of sulfur ylides: Grieco, JOC 1973, 38, 2572 (E):(Z) > 90:10 (70%) ■ Trisubstituted olefins via [2,3]-rearrangement of sulfonium ylides: – + 100 °C (–) is operationally equivalent to: (–) Accts. Chem. Res. 1974, 7, 147-55 [2,3] a a/g = 90:10 (95%) g a (E):(Z) > 97:3 (80-85%) 25 °C Et2NH, MeOH – (Z)-path (E)-path ‡ ‡ D. A. Evans [2,3]-Sigmatropic Rearrangements: Olefin Geometry Chem 206 favored disfavored
D. A. Evans [2, 3-Sigmatropic Rearrangements: Olefin Geometry Chem 206 a Trisubstituted olefins via [ 2, 3-rearrangemen An elegant squalene synthesis Ollis, Chem. Commun 1969, 99 日)pah R For study on this [2, 3]rxn See [2, 3 heat Baldwin (Z)-path One might project that the(E) path will be moderately favored with selectivity depending on size difference between rl& RM n-BuLi Li Rautenstrauch. Helv. Chim Acta 1971. 54. 739 This nxn is probably not as [2, 3 For related 2,3 rxns stereoselective as advertised Baldwin JACS 1969. 91. 3646 (E(z)=32 Me sP 140° NMe2 rave one major product in high yield OM Buchi JACS 1974. 96 5563 NMe2 poorly selective
Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me SPh X Y: RM RL Me Me Me OH S Me Me Me Me Me H OMe OMe NMe2 n-BuLi H X Y RM H RL H RL Y X RM H O Me Me Me C: NMe2 Me Me Me Me S Me Li Me Me Me Me Me SLi O Me Me NMe2 Me RM RL :X Y Y :X RL RM Me S Me Me Me Ph Me Me Me Me Me Me Me Me Me Me S Me Me S Me Me Me Me S Me Me Me Me S Me Me Me Me S Me Me Me Me F MgBr This rxn is probably not as stereoselective as advertised poorly selective 140 °C Buchi, JACS 1974, 96, 5563 Rautenstrauch, Helv. Chim Acta 1971, 54, 739 (E):(Z) = 3:2 For related [2,3] rxns See Baldwin JACS 1968, 90, 4758 Baldwin JACS 1969, 91, 3646 For study on this [2,3] rxn See Baldwin JACS 1971, 93, 6307 Squalene Li/NH3 "gave one major product in high yield" [2,3] – + benzyne heat PPh3 ® S=PPh3 An elegant squalene synthesis Ollis, Chem. Commun 1969, 99 [2,3] (RL = large) ■ Trisubstituted olefins via [2,3]-rearrangement: One might project that the (E) path will be moderately favored with selectivity depending on size difference between RL & RM (Z)-path (E)-path ‡ ‡ D. A. Evans [2,3]-Sigmatropic Rearrangements: Olefin Geometry Chem 206
