Download - PK Organometallics L4 2014m Tif
-
8/10/2019 PK Organometallics L4 2014m Tif
1/147
Organometallics in
Organic Synthesis
Pavel Koovsk
Charles University, Prague
-
8/10/2019 PK Organometallics L4 2014m Tif
2/147
1. Fundamentals
1.1. Introduction Zeise (1827), Frankland (1849),Grignard (~1900), Pauson (1951)
1.2. The 18-Electron Rule Exceptions: Ti, Zr, Ni, Pd, Pt - 16e -
Types of ligands (Ph 3P, CO;1
,2
,3
...)Electron book-keeping
1.3. Coordination of hydrocarbon ligands and its consequencesChatt-Dewar-Duncanson model
1.4. Fundamental reactions and catalytic cycles- coordination - dissociation- oxidative addition - reductive elimination- (migratory) insertion- -elimination - addition
-
8/10/2019 PK Organometallics L4 2014m Tif
3/147
2. Obtaining Complexes and Decomplexation
Three stages:
- Forming a complex- Reaction of the coordinated ligand- Release of the organic product
Examples of obtaining 1, 2, 4 .... complexes and decomplexation
-
8/10/2019 PK Organometallics L4 2014m Tif
4/147
3. Reactions of -Complexes withNucleophiles
3.1. Reactions of olefinic 2-complexesTwo different courses: ant i (Markovnikov); s y n (anti-Markovnikov)Pheromone synthesis (Semmelhack)
3.2. Reactions of allylic 3-complexes
Regioselectivity - less substituted carbonStereoselectivity - depends on the nucleophileSynthesis of flexibilene (McMurry)Carbonates, carbamates, protecting groups
3.3. Allylic rearrangements[3,3] Sigmatropic rearrangement catalyzed by PdAsymmetric versionDiastereoselective versionApplications
-
8/10/2019 PK Organometallics L4 2014m Tif
5/147
3.4. Reactions of 4- and 5-complexesStoichiometric functionalisation of dienes using Mo and Fe
(Birch, Pearson, Liebeskind)
Catalytic functionalisation of conjugated dienes(Bckvall reaction); Cl effectSynthesis of monarch butterfly pheromone ( Bckvall )Synthesis of bridged heterocycles ( Bckvall )Synthesis of heliotridane ( Bckvall )Carbocycles (Oppolzer)
4. Reactions of -Complexes4.1. Reactions involving an sp 3- or sp 2-carbon (Heck addition)
Heck reaction (mechanism, stereochemistry,asymmetric induction, chiral ligands)
ExamplesAppl.: Synthesis of 25-OH vitamin D (Trost)Pd(II) Pd(0) in s i tu
-
8/10/2019 PK Organometallics L4 2014m Tif
6/147
4.2. Reactions involving an sp 2-carbonHydrozirconationMethylzirconation (synthesis of farnesol)
Suzuki and Stille couplingsHartwig-Buchwald amination, aryl ethers
4.3. Reactions involving an sp-carbonAcetylide couplingSynthesis of calicheamicin 1I
-
8/10/2019 PK Organometallics L4 2014m Tif
7/147
5. Metallocarbenes
5.1. Tebbe Reaction
5.2. Metathesis and cyclopropanationCarbene generationIntramolecular cyclopropanation
5.3. Ring-closing metathesis (Grubbs and Schrock)CatalystsRing-closureMedium and large ring construction
5.4. Cyclopropanation
6. Cycloadditions6.1. Pauson-Khand reaction
6.2. Negishi cyclization
-
8/10/2019 PK Organometallics L4 2014m Tif
8/147
7. Oxidation
7.1. Epoxidation: Sharpless7.2. Epoxidation: Sharpless-Katsuki
7.3. Epoxidation: Yamamoto
7.4. Epoxidation: Jacobsen-Katsuki
7.5. Aziridination
7.6. Dihydroxylation
7.7. Aminohydroxylation
7.8. Hydrogen-transfer oxidation
-
8/10/2019 PK Organometallics L4 2014m Tif
9/147
8. Reduction 8.1. Catalytic hydrogenation of olefins
8.2. Catalytic hydrogenation of ketones
8.3. Transfer hydrogenation
9. Nucleophilic additions to C=O
9.1. 1,2-Addition
9.2. 1,4-Addition
10. C-H Activation 10.1. Aromatics
10.2. Allylic position
10.3. Ketone -position
10.4. Aliphatic C-H insertion
-
8/10/2019 PK Organometallics L4 2014m Tif
10/147
1. Fund amentals _____________________________________
1.1. In tro d u ctio n
New avenues in synthetic methodologyGoals that cannot be attained by othermeans (Mg, Cu, transition metals, . )
His tory
1827 Zeise salt (first organometallic cpd. with a transition metal)
William Christopher Zeise
-
8/10/2019 PK Organometallics L4 2014m Tif
11/147
1.1. Int r od uc t ion _____________________________________
1849 Sir Edward Frankland: Et 2Zn
1900 Victor Grignard: R Mg X
1951 Peter Pauson: ferrocene
(+ Wilkinson, Cotton, Woodward, and Rosenblum)
-
8/10/2019 PK Organometallics L4 2014m Tif
12/147
1.2. The 18-Electr o n Ru le _____________________________________
General desire to reach the e -configuration of thenearest noble gas, i.e., to have 18 e in valence shell(s 2p 6d 10 ).
-
8/10/2019 PK Organometallics L4 2014m Tif
13/147
1.2. The 18-Electr o n Ru le _____________________________________
Non-hy droc arbo n ligands
0 e : Lewis acids, e.g., AlCl 3 , BF 3 , etc.
1 e : halide, CN, H, (NO)
2 e : Lewis bases, e.g., R 3P, (RO) 3P, CO, RC N,
RN C, R 3N, R 2O, R 2S, etc.
3 e : NO
-
8/10/2019 PK Organometallics L4 2014m Tif
14/147
1.2. The 18-Electr o n Ru le _____________________________________
Hydroca rbon l igands
1 (1 e -): alkyl (R), aryl (Ar), -allyl2 (2 e -): olefins, carbenes (C=M)3 (3 e -): -allyl4 (4 e -): conjugated dienes5 (5 e -): dienyls, e.g., cyclopentadienyl (Cp)6
(6 e-
): conjugated trienes, arenes7 (7 e -): trienyls, e.g., cycloheptatrienyl8 (8 e -): cyclooctatetraene (COT)
-
8/10/2019 PK Organometallics L4 2014m Tif
15/147
1.2. The 18-Electr o n Ru le _____________________________________
Elect ron bo ok -keeping
Mo (CO) 6
6 + (6 2) = 18
(Ph 3P) 2Cp Ru Cl
(CO)2Cp Fe (CH
2=CH
2)
(2 2) + 5 + 8 + 1 = 18
(2 2) + 5 + 8 + 2 = 19
+
(2 2) + 5 + 8 + 2 - 1 = 18
-
8/10/2019 PK Organometallics L4 2014m Tif
16/147
1.2. The 18-Electr o n Ru le _____________________________________
Tutor ia l
-
8/10/2019 PK Organometallics L4 2014m Tif
17/147
1.3. Coord ina tion o f hyd rocarbon l igands _____________________________________
Chat t -Dew ar-Dunc anso n mo del
Joseph Chatt Michael Dewar
-
8/10/2019 PK Organometallics L4 2014m Tif
18/147
1.3. Coord ina tion o f hyd rocarbon l igands _____________________________________Consequences : Donation/back-donation and acidity of benzoic acid
Donat ion
Back-dona t ion
-
8/10/2019 PK Organometallics L4 2014m Tif
19/147
1.3. Coord ina tion o f hyd rocarbon l igands _____________________________________Consequences : Reactivity
-
8/10/2019 PK Organometallics L4 2014m Tif
20/147
1.3. Coord ina tion o f hyd rocarbon l igands _____________________________________Consequences : Stability
-
8/10/2019 PK Organometallics L4 2014m Tif
21/147
1.4. Fun dam ental React ion s and Catal. Cycles _____________________________________Metal - must be capable of temporary changing the number of sharedelectrons ( 18 16 14 )
-
8/10/2019 PK Organometallics L4 2014m Tif
22/147
1.4. Fun dam ental React ion s and Catal. Cycles _____________________________________Hydrogenation using Wilkinson catalyst ( catalyt ic cyc le )
-
8/10/2019 PK Organometallics L4 2014m Tif
23/147
2. Com plexat ion and decom plexat ion _____________________________________
Ap pl ica tion o f t rans i t ion m eta ls in o rg anic sy n thes i s :
- forming a complex (organic substrate + metal)- reaction of the coordinated organic molecule- release of the organic product
Stab i l i ty o f the com plexes :
Some are fairly stable (chromatography, crystallization,heat, air, moisture)
Some are highly unstable (inert atmosphere,water exclusion, low temp.)
-
8/10/2019 PK Organometallics L4 2014m Tif
24/147
2.1. 1 -Complexes _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
25/147
2.2. 2 -Complexes _____________________________________
Olef inic : Formation: by ligand exchange (Zeise salt)Decomplexation: ligand exchange
(Ph 3P, CO, pyridine, CN -)
Carbenes: Fischer complexes (free carbenes are extremely
unstable no decomplexation)Stabilization:
Ernst Otto Fischer
-
8/10/2019 PK Organometallics L4 2014m Tif
26/147
2.3. 4 -Complexes _____________________________________
Format ion :
Decomplexa t ion : - Oxidation (Me 3NO, Ce 4+ , FeCl 3)- Ligand exchange (Ph 3P)
-
8/10/2019 PK Organometallics L4 2014m Tif
27/147
2.4. 5 -Complexes _____________________________________
Format ion : Nucleophilic substitution
Decomplexa t ion : None really (very stable)Cp = spectator ligand
-
8/10/2019 PK Organometallics L4 2014m Tif
28/147
2.5. 6 -Complexes _____________________________________
Format ion : Ligand exchange (thermolysis)
Decomplexa t ion : Oxidation (Ce 4+ , I2, KMnO 4, O 2 /h )
-
8/10/2019 PK Organometallics L4 2014m Tif
29/147
3. Reactio n s o f -com plexes w i th n uc leophi les _____________________________________
Olefins normally do not react with nucleophiles.Coordination to a metal makes it possible.
-
8/10/2019 PK Organometallics L4 2014m Tif
30/147
3.1. Reactio n s o f o lefinic 2 -co m plexes (Pd) _____________________________________
Often highly regio- and stereo-selective ( s y n or anti )Pd - best understood (kermark) .
Bjrn kermark
-
8/10/2019 PK Organometallics L4 2014m Tif
31/147
3.1. Reactio n s o f o lefinic 2 -co m plexes (Pd) _____________________________________Orbital interactions in the palladium 2-complexes
-
8/10/2019 PK Organometallics L4 2014m Tif
32/147
3.1. Reactio n s o f o lefinic 2 -co m plexes (Pd) _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
33/147
3.1. Reactio n s o f o lefinic 2 -co m plexes (Pd) _____________________________________
Wacker oxidation
-
8/10/2019 PK Organometallics L4 2014m Tif
34/147
3.1. Reactio n s o f o lefinic 2 -co m plexes (Pd) _____________________________________
Wacker-Tsuji oxidation
-
8/10/2019 PK Organometallics L4 2014m Tif
35/147
3.1. Reactio n s o f o lefinic 2 -co m plexes (Pd) _____________________________________
Ap pl .: Pherom one syn thesis (Sem m elhack)
-
8/10/2019 PK Organometallics L4 2014m Tif
36/147
3.1. Reactio n s o f o lefinic 2 -co m plexes (Pd) _____________________________________
an ti
Ap pl .: R ing c los ure in s te ro ids (Ko o v s k )
-
8/10/2019 PK Organometallics L4 2014m Tif
37/147
3.1. Reactio n s o f o lefinic 2 -co m plexes (Pd) _____________________________________
Ap pl .: Isoxazol id ines (Ko o v s k )
-
8/10/2019 PK Organometallics L4 2014m Tif
38/147
3.2. Reactio n s o f al lyl ic 3 -complexes _____________________________________
Mainly Pd , some Mo , W, Ir , Rh , Fe
Mechan ism (Pd: Tsuji, Trost)
Regioselec t iv i ty (Tsuji, Trost, Hayashi )
Jiro Tsuji Tamio Hayashi
-
8/10/2019 PK Organometallics L4 2014m Tif
39/147
3.2. Reactio n s o f al lyl ic 3 -co m plexes (Pd) _____________________________________
Stereochemis t ry (Trost, Hayashi, Schwartz, Fiaud, Bckvall, Ko ovsk)
Barry Trost
-
8/10/2019 PK Organometallics L4 2014m Tif
40/147
144
3.2. Reactio n s o f al lyl ic 3 -co m plexes (Pd) _____________________________________
Appl . : Synthesis of Flexibilene (McMurry)
John McMurry
-
8/10/2019 PK Organometallics L4 2014m Tif
41/147
3.2. Reactio n s o f al lyl ic 3 -co m plexes (Pd) _____________________________________
Allyl carbonates - no base required (Tsuji):
Protection of OH and NH via allylic carbonates/carbamates(extremely mild and selective deprotection)
-
8/10/2019 PK Organometallics L4 2014m Tif
42/147
3.2. Reactio n s o f al lyl ic 3 -co m p lexes (Rh , Ir) _____________________________________
Oxygen nucleophiles (Evans, Hartwig, Helmchen, Ko ovsk ):
Stereochemistry
Paul Evans
Yellow
-
8/10/2019 PK Organometallics L4 2014m Tif
43/147
3.2. Reactio n s o f al lyl ic 3 -co m p lexes (Ir) _____________________________________
Oxygen nucleophiles with chiral ligands (Ko ovsk ):
Alexakis-Feringa ligand
Alex Alexakis Ben Feringa
-
8/10/2019 PK Organometallics L4 2014m Tif
44/147
3.3. A llyl ic rearrang em ents (Pd) _____________________________________
[3,3] Sigmatropic rearrangement catalyzed by Pd
Asymmetric version
Lary Overman
-
8/10/2019 PK Organometallics L4 2014m Tif
45/147
3.3. A llyl ic rearrang em ents (Pd) _____________________________________
Diastereoselective version
Applications
Andy Sutherland
4
-
8/10/2019 PK Organometallics L4 2014m Tif
46/147
3.4. Reactio n s o f al lyl ic 4 -complexes _____________________________________
Stoichiometric functionalisation of dienes using Mo and Fe (Birch, Pearson, Liebeskind, etc.).
Arthur Birch
Lanny Liebeskind
4
-
8/10/2019 PK Organometallics L4 2014m Tif
47/147
3.4. Reactio n s o f al lyl ic 4 -complexes _____________________________________
Tutorial : Explain the following transformations and rationalize thestereostructure of the intermediates and of the final product
f l l l 4 l ( l )
-
8/10/2019 PK Organometallics L4 2014m Tif
48/147
3.4. Reactio n s o f al lyl ic 4 -co m plexes (catalyt ic) _____________________________________Catalytic 1,4-functionalisation of dienes using Pd ( Bckvall reaction )
Jan Bckvall
3 4 R i f l l l i 4 l ( l i )
-
8/10/2019 PK Organometallics L4 2014m Tif
49/147
3.4. Reactio n s o f al lyl ic 4 -co m plexes (catalyt ic) _____________________________________
Chloride effect in Bckvall reaction:
3 4 R i f l l l i 4 l ( l i )
-
8/10/2019 PK Organometallics L4 2014m Tif
50/147
3.4. Reactio n s o f al lyl ic 4 -co m plexes (catalyt ic) _____________________________________
Tutorial : suggest the experimental conditions for the following transformations.
Which diastereoisomer of the starting compound will be suitable in part (c)?
3 4 R i f l l l i 4 l ( l i )
-
8/10/2019 PK Organometallics L4 2014m Tif
51/147
3.4. Reactio n s o f al lyl ic 4 -co m plexes (catalyt ic) _____________________________________
A p p l : Synthesis of the Monarch butterfly pheromone (Bckvall)
3 4 R i f l l l i 4 l ( l i )
-
8/10/2019 PK Organometallics L4 2014m Tif
52/147
3.4. Reactio n s o f al lyl ic 4 -co m plexes (catalyt ic) _____________________________________
A p p l : Bridged heterocycles - synthesis of tropane alkaloids (Bckvall)
-
8/10/2019 PK Organometallics L4 2014m Tif
53/147
3 4 R ti f l l l i 4 l ( t l t i )
-
8/10/2019 PK Organometallics L4 2014m Tif
54/147
3.4. Reactio n s o f al lyl ic 4 -co m plexes (catalyt ic) _____________________________________
A p p l : Spirocyclic heterocycles (Bckvall)
3 4 R ti f l l l i 4 l ( t l t i )
-
8/10/2019 PK Organometallics L4 2014m Tif
55/147
3.4. Reactio n s o f al lyl ic 4 -co m plexes (catalyt ic) _____________________________________
A p p l : Synthesis of heliotridane (Bckvall)
3 4 Reactio n s o fal lyl ic 4 co m plexes(catalyt ic)
-
8/10/2019 PK Organometallics L4 2014m Tif
56/147
3.4. Reactio n s o f al lyl ic 4 -co m plexes (catalyt ic) _____________________________________
A p p l : Carbocycles (Oppolzer)
Wolfgang von Oppolzer
4 Reactio n so f complexes
-
8/10/2019 PK Organometallics L4 2014m Tif
57/147
4. Reactio n s o f -complexes _____________________________________
4.1. React ion s in vo lvin g an s p 2 - or s p 3 -carbon
(Heck reactio n )
Richard Heck
4 1 Heckreactio n
-
8/10/2019 PK Organometallics L4 2014m Tif
58/147
4.1. Heck reactio n _____________________________________
Mechanism
:NEt 3
4 1 Heckreactio n
-
8/10/2019 PK Organometallics L4 2014m Tif
59/147
163
4.1. Heck reactio n _____________________________________
4 1 Heckreactio n
-
8/10/2019 PK Organometallics L4 2014m Tif
60/147
4.1. Heck reactio n _____________________________________
Enant iose lec t ive Heck react ion (Hayashi)
4 1 Heckreactio n
-
8/10/2019 PK Organometallics L4 2014m Tif
61/147
4.1. Heck reactio n _____________________________________
Stereodisc r im inat ing Heck react ion
In t ramo lecular Heck react ion - Unus ual regioselec t iv i ty
4 1 Heckreactio n
-
8/10/2019 PK Organometallics L4 2014m Tif
62/147
4.1. Heck reactio n _____________________________________
Catalyst: Pd (0) vs Pd (II); in s i tu generation of Pd( 0) from Pd( II):
4 1 Heckreactio n
-
8/10/2019 PK Organometallics L4 2014m Tif
63/147
167
4.1. Heck reactio n _____________________________________Multiple Heck reaction in complex synthesis: Vitamin D (Trost)
4 1 Heckreactio n
-
8/10/2019 PK Organometallics L4 2014m Tif
64/147
4.1. Heck reactio n _____________________________________
Tutor ia l : Exp la in the fo l lowing reac t ions
4 2 Cyclo fun ct io nal izat ion
-
8/10/2019 PK Organometallics L4 2014m Tif
65/147
4.2. Cyclo fun ct io nal izat ion _____________________________________Cycloo xyp al ladat ion - aryla tion
4 2 Cyclo fun ct io nal izat ion
-
8/10/2019 PK Organometallics L4 2014m Tif
66/147
4.2. Cyclo fun ct io nal izat ion _____________________________________Cycloam idop al ladat ion - arylat ion
4 3 React ion s Inv olv ing ans p 2 -Carbon
-
8/10/2019 PK Organometallics L4 2014m Tif
67/147
4.3. React ion s Inv olv ing an s p Carbon _____________________________________
Hydroz i rcona t ion
4 3 React ion s Inv olv ing ans p 2 -Carbon
-
8/10/2019 PK Organometallics L4 2014m Tif
68/147
4.3. React ion s Inv olv ing an s p Carbon _____________________________________
Methylz i rconat ion (Negishi react ion)
Ei-ichi Negishi
4.3.React ion s Inv olv ing ans p 2 -Carbon
-
8/10/2019 PK Organometallics L4 2014m Tif
69/147
4.3. React ion s Inv olv ing an s p Carbon _____________________________________
Coupl ing reac t ions sp 2 -s p 2
4.3.React ion s Inv olv ing ans p 2 -Carbon
-
8/10/2019 PK Organometallics L4 2014m Tif
70/147
174
4.3. React ion s Inv olv ing an s p Carbon _____________________________________
Makoto Kumada
Ei-ichi Negishi Tamejiro Hiyama
John Stille Akira Suzuki
Richard Heck
4.3.React ion s Inv olv ing ans p 2 -Carbon
-
8/10/2019 PK Organometallics L4 2014m Tif
71/147
4.3. React ion s Inv olv ing an s p Carbon _____________________________________
Suzuki -Miyaura co up l ing
EPSRC: If the reac t ion wo rks , why d o yo u need to kno w th e mechan i sm??
4.3. React ion s Inv olv ing an s p 2 -Carbon
-
8/10/2019 PK Organometallics L4 2014m Tif
72/147
. . g p _____________________________________
4.3. React ion s Inv olv ing an s p 2 -Carbon
-
8/10/2019 PK Organometallics L4 2014m Tif
73/147
g p _____________________________________
Anny Jutand
4.3. React ion s Inv olv ing an s p 2 -Carbon
-
8/10/2019 PK Organometallics L4 2014m Tif
74/147
g p _____________________________________
Examp les o f Suzuk i cou p l ing : o r tho-d i rec ted m eta ll at ion
Victor Snie kus
4.3. React ion s Inv olv ing an s p 2 -Carbon
-
8/10/2019 PK Organometallics L4 2014m Tif
75/147
g p _____________________________________
Examp les o f Suzuk i coup l ing :
4.3. React ion s Inv olv ing an s p 2 -Carbon
-
8/10/2019 PK Organometallics L4 2014m Tif
76/147
g p _____________________________________
Har twig-Bu chw ald coup l ing
John Hartwig
Steve Buchwald
L i g a n d key ro le
4.3. React ion s Inv olv ing an s p 2 -Carbon
-
8/10/2019 PK Organometallics L4 2014m Tif
77/147
g p _____________________________________
Har twig-Bu chw ald coup l ing : Mechan i sm
4.3. React ion s Inv olv ing an s p 2 -Carbon
-
8/10/2019 PK Organometallics L4 2014m Tif
78/147
g p _____________________________________
Har twig-Bu chw ald coup l ing : L i g a n d
4.3. React ion s Inv olv ing an s p 2 -Carbon
-
8/10/2019 PK Organometallics L4 2014m Tif
79/147
g _____________________________________
Har twig-Bu chw ald coup l ing : L i g a n d
Guy Lloyd-Jones(+ PK)
4.3. React ion s Inv olv ing an s p 2 -Carbon
-
8/10/2019 PK Organometallics L4 2014m Tif
80/147
_____________________________________
Har twig-Bu chw ald coup l ing : Lig and accelera t ion
Gregory Fu
4.4. React ion s Inv olv ing an sp -Carb on
-
8/10/2019 PK Organometallics L4 2014m Tif
81/147
_____________________________________Sonog ash i ra cou p l ing
Syn thes i s o f ca l icheamic in 1 I
Kenk-ichiSonogashira
Kyriakos C.Nicolaou
5. Metal lo carb enes
-
8/10/2019 PK Organometallics L4 2014m Tif
82/147
_____________________________________
5.1. Tebb e reacti o n
Frederick Tebbe
Reagent
Reaction
5.1. Tebb e reacti o n
-
8/10/2019 PK Organometallics L4 2014m Tif
83/147
_____________________________________
Appl ica t ion
Andy Holmes
5.2. Metathesis and Cyclo pr op anat ion
-
8/10/2019 PK Organometallics L4 2014m Tif
84/147
_____________________________________
Yves Chauvin Bob Grubbs Richard Schrock
5.2. Metathesis and Cyclo pr op anat ion
-
8/10/2019 PK Organometallics L4 2014m Tif
85/147
_____________________________________
Carbene g enerat ion
5.2. Metathesis and Cyclo pr op anat ion
-
8/10/2019 PK Organometallics L4 2014m Tif
86/147
_____________________________________
In te rmolecu lar cyc lop ropana tion
Rearrangements in vo lv ing oxon ium y l ides and inse r t ion in C-H bond
Louis Hegedus
Stephen Clark
5.3. Ring -Clos in g Metath esis
-
8/10/2019 PK Organometallics L4 2014m Tif
87/147
_____________________________________
Catalys ts
Ring-c losure
-
8/10/2019 PK Organometallics L4 2014m Tif
88/147
5.3. Ring -Clos in g Metath esis
-
8/10/2019 PK Organometallics L4 2014m Tif
89/147
_____________________________________
R in g c o n s t r u c t io n
5.3. Ring -Clos in g Metath esis
-
8/10/2019 PK Organometallics L4 2014m Tif
90/147
_____________________________________
Medium and l arge r ing c ons t ruc t ion
5.3. Ring -Clos in g Metath esis
-
8/10/2019 PK Organometallics L4 2014m Tif
91/147
_____________________________________
Other r ings co ns t ruc t ion
-
8/10/2019 PK Organometallics L4 2014m Tif
92/147
196
5.4. Cyclo pr op anat io n
-
8/10/2019 PK Organometallics L4 2014m Tif
93/147
_____________________________________
S im m o n s S m i t h
5.4. Cyclo pr op anat io n
-
8/10/2019 PK Organometallics L4 2014m Tif
94/147
_____________________________________
D ia zo c o m p o u n d s
-
8/10/2019 PK Organometallics L4 2014m Tif
95/147
5.4. Cyclo pr op anat io n _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
96/147
_____________________________________
Diazo com pou nds - in t ramolecu lar
6. Cyclo add i t ion s _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
97/147
6.1. Paus on -K hand react io n
Peter Pauson
Billy Kerr
6.1. Paus on -K hand react io n _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
98/147
6.1. Paus on -K hand react io n _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
99/147
Catalyt ic and enant ios e lec t ive vers ion
6.2. Negish i cy clizat ion _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
100/147
7. Oxid ation _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
101/147
7.1. Epo xid at ion : Sharpless
-
8/10/2019 PK Organometallics L4 2014m Tif
102/147
7.2. Epo xid at ion : Sharp less -K atsuk i _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
103/147
Mechan ism and s t e reoch emis t ry
7.2. Epo xid at ion : Sharp less -K atsuk i _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
104/147
Examples
7.2. Epo xid at ion : Sharp less -K atsuk i _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
105/147
Racemate reso lut ion
Chemo select ive epoxid at ion
7.2. Epo xid at ion : Sharp less -K atsuk i _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
106/147
De nov o syn thes i s o f ca rbohydra tes
ill Roush
7.2. Epo xid at ion : Sharp less -K atsuk i _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
107/147
De nov o syn thes i s o f ca rbohydra tes
7.2. Epo xid at ion : Sharp less -K atsuk i _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
108/147
De nov o syn thes i s o f ca rbohydra tes
7.3. Epo xid at ion : Yamam oto _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
109/147
Hisashi Yamamoto
Advantages:- No water sensitivity
- Low catalyst loadingDisadvantages:
- Vanadium is more expensive- Long reaction times
(e.g., -20 oC, 4 days)
7.4. Epo xid at ion : Jacob sen-Katsu ki _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
110/147
Eric Jacobsen
- Works ONLY with c is -olefins- NOT effective with allylic ROH
7.4. Epo xid at ion : Jacob sen-Katsu ki _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
111/147
Catalys t des ign
7.4. Epo xid at ion : Jacob sen-Katsu ki _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
112/147
Epox idat ion (c is -o lef ins)
7.4. Epo xid at ion : Jacob sen-Katsu ki _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
113/147
Stereospeci f ic i ty
Radical s tabi l izat ion (by co nju gat ion) enc ou rages radica l mech anism .
7.4. Epo xid at ion : Jacob sen-Katsu ki _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
114/147
Examples
7.4. Epo xid at ion : Jacob sen-Katsu ki _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
115/147
App l .: Syn thes i s o f Cromaka lim
App l .: Syn thes i s o f Ind inav i r scaffo ld
Tutor ia l : (1) Identify the absolute configuration of Salen ligand required.(2) Show the mechanism for the formation of s y n -amino alcohol.
7.5. A zirid in ation _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
116/147
7.6. Dihyd ro xy lat ion _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
117/147
Upjohn catalytic method
-
8/10/2019 PK Organometallics L4 2014m Tif
118/147
7.6. Dihyd ro xy lat ion : enant ios elect iv i ty _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
119/147
Scaffold: pseudoenantiomers Ligands: C 2- symmetrical pseudoenantiomers
7.6. Dihyd ro xy lat ion : enant ios elect iv i ty _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
120/147
7.7 . A m inhy dro xyla t ion _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
121/147
Reagent and catalyst
Catalytic cycle
7.7 . A m inhy dro xyla t ion : enant iose lec t iv i ty _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
122/147
7.8. Hyd ro gen-t rans fer ox idat ion _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
123/147
8. Redu ct io n _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
124/147
Hydrogena t ion
William Knowles
Henri Kagan
Catalyt ic hy drog enat ion
L i g a n d s
Ryoji Noyori
8.1. Hyd ro g enation o f C=C _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
125/147
Xumu
Zhang
Andreas
Pfaltz
Frank
Glorius
8.1. Hyd ro g enation o f C=C _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
126/147
Rh : Requ i res a coord ina t ing g roup in the m olecu le.
8.1. Hyd ro g enation o f C=C _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
127/147
Rh
8.1. Hyd ro g enation o f C=C _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
128/147
Ru : - Broader sco pe than Rh (e .g . , do es no t require amide m oiety).
- High er pressure
8.1. Hyd ro g enation o f C=C _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
129/147
Ru and C=C
8.1. Hyd ro g enation o f C=C _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
130/147
Ru and C=C
8.1. Hyd ro g enation o f C=C _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
131/147
Ir and C=C
8.2. Hyd ro g enation o f C=O _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
132/147
Ru and C=O
-
8/10/2019 PK Organometallics L4 2014m Tif
133/147
-
8/10/2019 PK Organometallics L4 2014m Tif
134/147
8.3. Transfer hy dr og enat ion _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
135/147
Ru : Dynamic racemate resolut io n
9. Nucleoph i l ic add i t ion to c arbon yl d er iva tives _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
136/147
9.1. 1,2-A d d itio n
9.1. 1,2-A d d itio n _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
137/147
9.2. 1,4-A d d itio n _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
138/147
10. C-H Ac tivatio n _____________________________________10 1 A ro m atics
-
8/10/2019 PK Organometallics L4 2014m Tif
139/147
10.1. A ro m atics
10.1. A ro m atics _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
140/147
10.1. A ro m atics _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
141/147
10.1. A ro m atics _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
142/147
10.2. A l lyl ic po si t io n _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
143/147
10.3. Keto n e -pos i t ion _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
144/147
10.4. A liph atic C-H in sert io n _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
145/147
10.4. A liph atic C-H in sert io n _____________________________________
-
8/10/2019 PK Organometallics L4 2014m Tif
146/147
-
8/10/2019 PK Organometallics L4 2014m Tif
147/147