Sharpless epoxydation of allylic alcohols

Wykład 6

Sharpless epoxydation of allylic alcohols H H D-(-)-Diethyl tartarate.. : : 3 2 : Ọ. : 1 H (CH 3 ) 3 CH, Ti(iPr) 4 CH 2 Cl 2-20 o C 2 1 H 3 -(+)-Diethyl tartarate H H

Green Chemistry

Asymmetric epoxydation of alkyl- and aryl-substituted alkenes

Suplement Competing channels of the Jacobsen-Katsuki reaction.

Typy eakcji z Udziałem Kompleksów Metali Przejściowych eakcje podstawienia (substytucji) i insercji: - liczba koordynacyjna nie ulega zmianie eakcje przyłączania (addycji) : - wzrasta liczba koordynacyjna metalu eakcje dysocjacji (eliminacji): - liczba koordynacyjna maleje eakcje utleniania i redukcji: -następuje zmianami stopnia utlenienia metalu eakcje reduktywnej eliminacji i addycji utleniającej: - zmienia się liczba koordynacyjna i stopień utlenienia metalu

Palladium in homogeneous catalysis of C-C coupling reactions - promote all mechanistically essential elementary reactions: - ligand dissociation - oxidative addition - insertion - reductive elimination - β-h elimination - tolerance of numerous functional groups - relatively low sensivity of organyls to air and water - low toxicity - economic advantages relative to h, Ir, Pt

Palladium(0) catalyzed oxidative addition/transmetalation ' ' ' 0 0 reductive elimination II oxidative addition II C insertiontion 'M' II ' II II ' rearrangement M' transmetalation II '

Stille reaction 1 1 2 2 1 2 1 1 Bu 3 Sn Bu Bu Bu Sn + + 2 SnBu 3 2 1

Heck reaction the oxidative addition/alkene insertion process Z Z (0) H oxidative addition reductive elimination (II) (II) H Z coordination β-eliminaction H H Z

Catalytic cycle for Heck eaction (Ac) 2 + n PPh 3 (Ac) 2 (PPh 3 ) 2 HNEt 3 + PPh 3 ()PPh 3 + H + [ 0 (PPh 3 ) 2 (Ac) ] - NEt 3 H(Ac)(PPh 3 ) 2 [ (Ac)(PPh 3 ) 2 ] - Z (Ac)(PPh 3 ) 2 H Z (Ac)(PPh 3 ) 2 - Z Nam T.S. Phan et al.. Adv. Synth. Catal. 2006, 348, 609.

Palladium(0)-catalyzed carbonylation of halides C Nuc H C Nu (0) oxidative addition (II) C (II) insertion H (II) C ' M ' transmetalate reductive elimination C ' (M = Sn, Zn, etc.) H

Formation of π-allylpalladium complexes n + n 0 Nuc Nuc II Y II 2 (H) (H) + H II II 2 H + 2 H B II 2

Palladium(0) catalyzed reactions of allylic substrates Nuc n 0 II σ π H H Nuc 0 Nuc - (+) II II 'M II ' II n 0 '

Stereochemistry of -catalyzed allylic substitution [M] - - INV [M]=coordinatively unsaturated complex fragment e.g. (P 3 ) 2 Nu (soft) [M] distal proximal Nu (hard) INV ET Nu [M] [M-Nu] net ET Nu Nu [M] -[M] Soft nucleophile stabilized carboanions as well as S, N, P and certain nucleophiles Hard nucleophiles Mg and 2 Zn net INV Nu

Asymmetric Allylic Alkylation - Enantioselective catalysis complex formation isomerization Y + [M*] k 1 k -1 [M*] k j very fast [M*] k' 2 Nu k'' 2 fast slow Nu Nu enantiomerically pure for k'' 2 [Nu] < k' 2 [Nu] < k j

eaction of (II)-alkene complexes + Cl 2 (MeCN) 2 0 o C fast Cl Cl π-alkene (II) Nuc - Nuc + HCl + (0) Nuc H Cl σ-alkyl (II) β-elimination 'M M=Sn,Zr,Zn, Cu,B,Al,Mg C H 2 >-20 o C or H - Cl Nuc ' Nuc Cl Nuc C Nuc + (0) H reductive elimination Nuc H Cl Nuc ' + (0) Cl Nuc β-elimination MeH Nuc + (0) =H,Ph,,C 2, CN,Cr,Ac,NHAc (less substituted) Nuc Me + (0)

Palladium(II) assisted alkylation of alkenes Cl 2 + Y (-) (0) Cl Cl 2 Y (-) Et 3 N -78 o C Cl Cl NEt 3 C MeH -20 o C (-) Y Y Et 3 N H 2 25 o C 25 o C NEt 3 Cl Y Y Y, Y= C 2, C, CN = H, Ph, Me, Bu, AcNH + C 2 Me + + (0) (0) (0)

Stereoselective synthesis of tri- and tetrasubstituted alkenes Br nbu 90%, 98% (Z) MeZnBr 5% [Cl 2 (dpephos)] inversion MeZnBr 2% [(tbup) 2 ] retention nbu Me 85%, 98% (Z,E) Me nbu 93%, 98% (E,E) PPh 2 PPh 2 dpephos eiser., Angew. Cem. Int. Ed., 2006, 45, 2838

Konfiguracja elektronowa karbenów C. M. p π p π p π p π σ 1 p π 1 σ 2 p π 2 σ 1 p π 1 Stan: trypletowy singletowy wzbudzony podstawniki σ-donorowe E p π σ E > 2, stan trypletowy; E < 2 stan singletowy

Wpływ elektronowy podstawników.. 2 N.... N 2 2 B.. B 2.. 2 P.. Si' 3 π-donor / σ-atraktor π- atraktor / σ-donor π-donor / π-akceptor

Kompleksy karbenów kompleks Fischera donorowo-akceptorowy kompleks Schrocka kowalencyjny C σ M C σ M C π M C Mn C π M = lub inna π- donorowa grupa, niski stopień utlenienia M = alkil /wysoki stopień utlenienia M

Metateza - katalizatory N Mo Ar H CMe 2 Ph Cl PCy 3 Cl u PCy 3 Ph MesN Cl Cl u NMes N 2 Ar = 2,6-(i-Pr) 2 C 6 H 3 = (F 3 C) 2 (CH 3 )C Schrock, 1990 Grubbs, 1995 Hoveyda-Grela, 2002

Karben Fishera dla chromu Me Me Me Me Cr(C) 4 Br (a) Bui (b) Cr(C) 6 (c) Me 3 BF 4 Cr(C) 5 + Me Me Me Me

Karben Fishera jako katalizator N Cr(C) 5 + Et 125 o C, 5 h DMF, 95% Et N Et Et

Metateza olefin 1 1 1 kat + + 1 SM self-metathesis 1 1 1 2 kat + + 2 1 2 2 CM cross-metathesis kat + CM ring-closing metathesis M ring-opening metathesis kat n MP ring-opening-metathesis polymerization ADMET acycylic-diene-metathesis polymerization n +

Mechanizm reakcji HC CH 2 6 M CH 2 HC CH 1 M CH 2 C H CH 2 5 M CH 2 HC CH 2 M CH 2 CH 2 HC M CH 2 HC CH HC CH 2 4 M CH 2 CH HC 3 H 2 C CH 2

Metateza w zaawansowanej syntezie organicznej (CH 2 ) 7 (CH 2 ) 7 WCl 6, Cp 2 TiMe 2 + (CH 2 ) 8 (CH 2 ) 7 TBS Grubbs cat. TBS H N boc -CH 2 CH 2 N N boc 59% NH N Mo CMe 2 Ph Me Me Me Me 22 0 C, 5 min Me H Me Me + 93%, 99% ee

Metateza zastosowanie w przemyśle N boc + CH 2 SiMe 3 Grubbs cat. boc N CH 2 SiMe 3 83%, E/Z = 1:3.2 ucl 3 /HCl BuH * n * norsex () (Elf-Atochem) 90% trans WCl 6 / WCl 4 * * telene () (Goodrich) n metton () (Hercules)

Metateza alkinów 1 cat. (t-bu) 3 W C t-bu + 1 2 2 cat. H 2

Mechanizm metatezy mieszanej alkin-alken M M M M M M [M] A [M] E [M]

1,3 migration H PH 3 Br H 3 P H Br 3 2 1 1-cis 1-trans

1,5 migration H 3 P 5 H Br 1 H 3 P Br H 4 2 3 5-cis 5-trans

Possible mechanism operating for intramolecular 1,n aryl-to-aryl palladium shifts 1,3 migration Sterically hindered High energy (IV) transition state Direct transfer (IV) mechanism only 1,4 migration Geometrically constrained (i.e. phenanthrene) Geometrically unconstrained (i.e. biphenyl) (IV) transition state Direct transfer (II) transition state Direct transfer (IV) transition state Direct transfer Both (II) and (IV) mechanisms competing 1,5 migration Geometrically constrained (i.e. benzo[c]phenanthrene) Geometrically unconstrained (i.e. benzylbenzene) ow energy (II) transition state Direct transfer Absence of a (IV) machanism ow energy (II) transition state Direct transfer (IV) transition state Two-step transfer (IV) mechanism favored 1,6 migration ow energy (II) transition state Direct transfer (IV) transition state Two-step transfer (IV) mechanism favored