Chapter 10 Pericyclic Reactions （周环反应）

Pericyclic Reactions • Continuous concerted reorganisation of electrons • 5 major categories: – Electrocyclic ring opening/closure – Cycloaddition/cycloreversion reactions – Cheletropic reactions (e.g. carbene addition) – Group transfer reactions (e.g. H 2 – Sigmatropic rearrangements transfer)

Sigmatropic Rearrangements • Migration of a s -bond across a conjugated p -system • [

m

,

n

] shift when the s -bond migrates across

m

one system and

n

of another atoms of 3 2 1 R 1' [1,3]-shift 3 1' R 2 1 1 2 R 1' 2' 2 3 [3,3]-shift 1 3' R 1' 2' 3 3'

p p  Conjugated

π

Systems Antibonding  4  3  3  2 nonbonding  2  1  1 Bonding 2 p-orbitals 3 p-orbitals 4 p-orbitals

Suprafacial/Antarafacial • Suprafacial migration: Group moves across same face R R' R R' R' R R R' R R' R R' • Antarafacial migration: Group moves from one face to the other R R' R' R' R R' R R R R' R R'

FMO Analysis • [1,3] Sigmatropic Rearrangements: H migration H H + H R R' R R' R R' 1s proton LUMO  2 allyl anion HOMO R H R' R H R' Suprafacial migration

FORBIDDEN

Antarafacial migration

ORBITALLY ALLOWED BUT H CANNOT BRIDGE DISTANCE

FMO Analysis • [1,3] Sigmatropic Rearrangements: C migration CH 3 H 3 C + R R' R R' R CH 3 R' 2p Carbon LUMO H C H H  2 allyl anion HOMO R R' Suprafacial migration Retention at carbon

FORBIDDEN

H C H H R R' Suprafacial migration Inversion at carbon

ALLOWED

FMO Analysis • [1,5] Sigmatropic Rearrangements R X R'  3 pentadienyl anion HOMO R H X + X R' R R' 1s proton LUMO Suprafacial migration

ALLOWED

Antarafacial migration

FORBIDDEN

C 2p carbon LUMO  3 pentadienyl anion HOMO Suprafacial migration Retention at Carbon

ALLOWED

C Antarafacial migration Inversion at Carbon

ALLOWED

Dewar-Zimmerman • Dewar-Zimmerman model: – Choose a set of 2p atomic orbitals and arbitrarily assign phase – Connect the orbitals in the starting material – Allow reaction to proceed according to postulated geometry and connect reacting lobes.

– Count number of phase inversions: Odd = Möbius, Even = Hückel – Assign transition state as aromatic or antiaromatic based on number of electrons:

System

Hückel

Aromatic

4n + 2

Antiaromatic

4n Möbius 4n 4n + 2 – Aromatic = Thermally allowed (Photochemically forbidden) – Antiaromatic = Thermally forbidden (Photochemically allowed)

Dewar-Zimmerman • [1,3]-H shift H • [1,5]-H shift R R H H H H R' R R' Suprafacial: Two Phase Inversions Hückel Topology Four electrons

FORBIDDEN

Antarafacial: Three Phase Inversions Möbius Topology Four electrons

ALLOWED

H R' R R' Suprafacial: Zero Phase Inversions Hückel Topology Six electrons

THERMALLY ALLOWED

H H

Woodward-Hoffman •

A ground-state pericyclic change is symmetry-allowed when the total number of (4q+2) odd.

s and (4r) a components is

• [1,5]-H shift – suprafacial H H s 2 s H p 4 s No. (4q+2)s = 1 No. (4r)a = 0 Total = 1

ALLOWED

• [1,5]-H shift – antarafacial H s 2 s H p 4 a No. (4q+2)s = 1 No. (4r)a = 1 Total = 2

FORBIDDEN

H

Woodward-Hoffman • [1,7]-H shift – antarafacial p 6 a H No. (4q+2)s = 1 No. (4r)a = 0 Total = 1

ALLOWED

H H s 2 s R • [3,3] rearrangement R Chair p 2 s p 2 s s 2 s R No. (4q+2)s = 3 No. (4r)a = 0 Total = 3

ALLOWED

Boat p 2 s p 2 s s 2 s R No. (4q+2)s = 3 No. (4r)a = 0 Total = 3

ALLOWED

[1,2] Sigmatropic Rearrangements • [1,2]-C shift to cation: Wagner-Meerwein Rearrangement R R 2p Carbon radical C OH H +  1 olefin radical cation Suprafacial migration:

ALLOWED

• R [1,2]-C shift to anion: Wittig Rearrangement R 2p Carbon radical O R BuLi R O Li  2 olefin radical anion C Suprafacial migration:

FORBIDDEN

 Must be stepwise

[2,3] Sigmatropic Rearrangements R * X Y R' X, Y = C, N, O, S, Se, P • FMO Analysis R X Y R'  2 vinyl radical X Y  2 allyl radical R * R' X Y Suprafacial migration

ALLOWED

[2,3] Sigmatropic Rearrangements • X=O, Y=C Wittig Rearrangement 1 [2,3] BuLi O O Ph Li + LiO Ph Ph • X=S, Y=C Sulfonium Ylide Rearrangement 2 BuLi S + S 1.

2.

Baldwin, JACS 1971 ,

93

, 3556 Lythgoe, Chem. Comm. 1972 , 757 S + S Li + [2,3] S S

[2,3] Sigmatropic Rearrangements • • X=N, Y=C Ammonium Ylide Rearrangement 3 (Stevens) R R R BuLi [2,3] N + N + Li + Me 2 N CN CN CN X=C, Y=C All-carbon Rearrangement 4 Cu(I) -N 2 O O N 2 H 3.

4.

Buchi, J. Am. Chem. Soc. 1974 ,

96

, 7573 Smith, J. Org. Chem. 1977 ,

42

, 3165 [2,3] O ROH O OR

[2,3] Sigmatropic Rearrangements • X=N, Y=O Meisenheimer Rearrangement 5 R R [2,3] Zn/HOAc Et Et N + O Et N O Et OH R • X=S, Y=O Sulfoxide Rearrangement 6 Ph S + O (MeO) 3 P MeOH [2,3] S O Ph BuLi PhSCl 5.

6.

Tanabe, Tet. Lett. 1975 , 3005 Evans, Accts. Chem. Res. 1974 ,

7

, 147 OH

[2,3] Sigmatropic Rearrangements • X=Se, Y=N Related Rearrangement 7 • Ph Ph [2,3] MeOH Ph Se + N Ts Se Ph N Ts X=S, Y=N Related Rearrangement 8 Ph NHTs TsO TsO SPh 7.

8.

NaN(Cl)Ts (MeO) 3 P MeOH Ph S + N Ts Hopkins, Tet. Lett. 1984 ,

25

, 15 Dolle, Tet. Lett. 1989 ,

30

, 4723 [2,3] TsO PhS N Ts N Ts

[2,3] Sigmatropic Rearrangements • – Olefin Selectivity from starting olefin 1,2-Disubstitution(E) R X Y R' R R' H H X Y Y X H R R' H R X Y R X Y – R and R’ prefer to sit in pseudo-equatorial positions 9 R' R' 9.

O CO 2 H Nakai, Tet. Lett. 1981 ,

22

, 69 2 LDA H O CO 2 H (E) selectivity: 75%

[2,3] Sigmatropic Rearrangements • – Olefin Selectivity from starting olefin 1,2-Disubstitution(Z) R X Y H R H R' X Y R' Y X R' R H H – R X Y R X Y R' R' Generally, higher levels of 1,3 induction seen with Z olefins 10 R BuLi R Bu 3 Sn O OH Only E isomer obtained 10.

Still, J. Am. Chem. Soc. 1978 ,

100

, 1927

[2,3] Sigmatropic Rearrangements • – Olefin Selectivity from starting olefin (E)-Trisubstituted R X Y R' R R' H H X Y Y X H R R' H – R X Y R X Y R' R' E transition state still generally preferred but R-Me interaction may cause significant destabilisation 10 n-Bu Bu 3 Sn O BuLi n-Bu OH >96% Z isomer

[2,3] Sigmatropic Rearrangements • – Olefin Selectivity from starting olefin (Z)-Trisubstituted R R X Y H R' H X Y R' Y X R' R H H – R X Y R X Y Again, generally higher levels of 1,3 induction seen with Z olefins due to highly destabilising R R’ interaction R' R'

[2,3] Sigmatropic Rearrangements • Olefin Selectivity from allylic position – R R' X R > R' Y R X Y R' H H Y X H R H R' R R' R' X Y R X Y May expect selectivity dependent on size difference of R vs. R’ 11 SLi BuLi R (E):(Z) = 3:2 S R 11.

Rautenstrauch, Helv. Chim. Acta 1971 ,

54

, 739

[2,3] Sigmatropic Rearrangements • Chiral Auxiliaries 12 O O O N ROCH 2 – Via: CH 2 OR BuLi ROCH 2 Li O ROCH 2 O M O N CH 2 OR N CH 2 OR 12.

Katsuki, Tet. Lett. 1986 ,

27

, 4577 H O O N ROCH 2 96% de CH 2 OR

[2,3] Sigmatropic Rearrangements • Internal Relay of Stereochemistry 13 O SnBu 3 O O BuLi H O – Via: (Felkin-Ahn) O C H O H O O O ratio 79:6 H O O O 13.

Bruckner, Angew. Chem. Int. Ed. 1988 ,

27

, 278

[2,3] Sigmatropic Rearrangements • Steric Effects Y X Y X t-Bu t-Bu Y X t-Bu t-Bu – Pseudo-equatorial attack generally favoured 14 N 2 S + Ph CO 2 Et Cu(I) SPh t-Bu CO 2 Et selectivity 91:9 14.

Evans, J. Am. Chem. Soc. 1972 ,

94

, 3672

[2,3] Sigmatropic Rearrangements • Ring Expansion 15 CO 2 Et S Cu(I) N 2 CHCO 2 Et S + [2,3] S CO 2 Et • Ring Contraction 16 O Br Ph N + O MeO Ph MeOH N O Ph N O " N + Ph " N O Ph 15.

16.

Vedejs, Accts. Chem. Res. 1984 ,

17

, 358 Stevenson, Tet. Lett. 1990 ,

31

, 4351

[3,3] Sigmatropic Rearrangements • FMO Analysis X Y X Y X Y  2 allyl radical Chair geometry

ALLOWED

Boat geometry

ALLOWED

• Dewar-Zimmerman Zero Phase Inversions Hückel Topology Six electrons

THERMALLY ALLOWED

[3,3] Sigmatropic Rearrangements X Y X X, Y = C, O, N, etc Cope X X Y X Y O Claisen O • Cope Rearrangement: Boat vs. Chair Transition State 17 trans-trans 17.

Doering, Roth, Tetrahedron 1962 ,

18

, 67 trans-cis cis-cis

[3,3] Sigmatropic Rearrangements • Cope Rearrangement: Boat vs. Chair Transition State H H Me Me trans-trans 90% Me H Me H Me Me H Me H Me H H cis-cis 10% Me H Me H Me H Me H trans-cis <1% Me Me H H Me H H Me trans-cis 99.7% Me Me H H Me H H Me trans-trans 0.3%

[3,3] Sigmatropic Rearrangements • Cope Rearrangement: Use of ring strain 18 H 5-20°C – H Relief of ring strain upon rearrangement • Oxy-Cope Rearrangement 19 H 220°C k eq ~ 10 5 – OH OH Tautomerism shifts equilibrium to right 18.

19.

Brown, Chem. Comm. 1973 , 319 Marvell, Tet. Lett. 1970 , 509 O

[3,3] Sigmatropic Rearrangements • Oxy-Cope Rearrangement H O k 1 H O O O k 2 O 10 10 < k 2 < 10 17 k 1 20.

– – Significant rate acceleration for anionic Oxy-Cope.

20 Counter-ion also important OX

OX Half-life

MeO OX 66°C THF Golob, J. Am. Chem. Soc. 1975 ,

97

, 4765 H H OMe OH OLi ONa OK OK O K + (66 yrs) No rxn 1.2 hrs 1.4 min 11 hrs 4.4 min

T/

°

C

66 10

[3,3] Sigmatropic Rearrangements X • Claisen Rearrangement X O O – – X = C, H, O, N Thermodynamic driving force: (C-O) p -bond and (C-C) s -bond formation X=Heteroatom leads to higher exothermicity and reaction rate O H ~30 O OR ~20 ~20 kcal/mol O H ~30 kcal/mol O OR

[3,3] Sigmatropic Rearrangements • Synthesis of allyl vinyl ethers 21,22 OH Hg(OAc) 2 OEt AcOHg OEt O O O Ph O Ph O Cp 2 Ti Cl AlMe 2 21.

22.

Watanabe, Conlon, J. Am. Chem. Soc. 1957 ,

79

, 2828 Evans, Grubbs, J. Am. Chem. Soc. 1980 ,

102

, 3272

[3,3] Sigmatropic Rearrangements • Endocyclic Olefins 23 Et O Via Chair intermediate: O 144°C Et t-Bu O t-Bu • t-Bu Exocyclic Olefins 24 diastereoselection >87:13 EtO O O t-Bu OEt t-Bu t-Bu 23.

24.

– Overlap equally good from either face Ireland, J. Org. Chem. 1983 ,

48

, 1829 House, J. Org. Chem. 1975 ,

40

, 86 ratio 52:48 O OEt

[3,3] Sigmatropic Rearrangements • Olefin Selectivity CHO O Me O H H Me O CHO – R group prefers to sit in pseudo-equatorial position 25 R' O R 110°C R' R CHO (E) R' R CHO (Z)

R

Me Me Et

R’

Et i-Pr Et

(E):(Z)

90:10 93:7 90:10 25.

Faulkner, J. Am. Chem. Soc. 1973 ,

95

, 553

[3,3] Sigmatropic Rearrangements • Olefin Selectivity Me X Et H O O X Et Et X Me Me H O – Extra substituents lead to enhanced diastereoselection 25 Larger X => better selectivity Et Et

X

H Me MeO Me 2 N Me

(E):(Z)

90:10 >99:1 >99:1 >98:2 Me O O X X

[3,3] Sigmatropic Rearrangements • • Claisen Variants: Johnson Orthoester Claisen 26 OH MeC(OEt) 3 H + EtO O OEt O OEt Claisen Variants: Eschenmoser Claisen 27 O OEt OH MeO NEt 2 MeO Xylene 150°C MeO O NEt 2 O NEt 2 O NEt 2 26.

27.

Johnson, Faulkner, Peterson, J. Am. Chem. Soc. 1970 ,

92

, 741 Eschenmoser, Helv. Chim. Acta 1964 ,

47

, 2425

[3,3] Sigmatropic Rearrangements • Claisen Variants: Ireland Enolate Claisen 28 O OTMS OH LDA O O O TMSCl 28.

29.

– R' Substituted enolates afford an additional stereocentre 29 R R O R' O R' H H OTBS OTBS O OTBS R R' R H R O R' R O R' O H OTBS OTBS Ireland, J. Am. Chem. Soc. 1976 ,

98

, 2868 Ireland, J. Org. Chem. 1991 ,

56

, 650 OTBS

[3,3] Sigmatropic Rearrangements • Lewis Acid catalysed Claisen rearrangement LA LA O + LA O + O O LA – Presence of Lewis Acid can influence rearrangement 30 R O R X O X R O X Lewis Acid R LA O X R X LA O 30.

Yamamoto, J. Am. Chem. Soc. 1990 ,

112

, 316

[3,3] Sigmatropic Rearrangements • • O Chiral Lewis Acid promoted Claisen rearrangement 31 Si(t-Bu)Ph 2 Ph Ph (R)-

1

1.1 - 2 eq 88% ee O Al O Me DCM, -20°C O SiMe 3 O SiMe 3 Si(t-Bu)Ph 2 (R)-

1

O Enantioselective Claisen Rearrangements 32 OBL 2 OH L 2 BBr i-Pr 2 NEt DCM O -20°C O >97% ee ArO 2 S Ph OBL 2 OH N B Br N L 2 BBr Et 3 N PhMe O -20°C O 96% ee Ph L 2 BBr SO 2 Ar 31.

Yamamoto, J. Am. Chem. Soc. 1990 ,

112

, 7791 32. Corey, J. Am. Chem. Soc. 1991 ,

113

, 4026

[m,n] Sigmatropic Rearrangements • [4,5] shift Ph Ph NMe 2 NMe 2 MeONa Ph NMe 2 [4,5] – [2,3] possible but [4,5] favoured. [2,5] and [3,4] forbidden • [3,4] shift MeO O MeO OH OMe OH

• C=C + X: 1-6 Key Retrons R R X R' R R' XH H X R' • C=C + X: 1-5 R R' R X X R' R • C=C + X: 1-4 X H R R' R' X R' Cope rearrangement Retro-ene reaction Claisen rearrangement [2,3] rearrangement Wittig X=O Ene reaction H X R'