Decarboxylative allylation with other electron withdrawing groups

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Carbonylation of sp-hybridized carbon atoms

Only few examples of carbonylation at C-sp atoms are described in the literature. The first one was reported by Tsuji in 1980. The carbonylation of phenyl acetylene with palladium chloride for the synthesis of propiolate esters was reported (Scheme 16). The mechanism remains unclear. Palladium acetylides may be involved, and the copper(II) salt should act as the final reoxidant. Jiang extended this reaction to various alcohols (n-BuOH, i-PrOH) yielding the desired esters in similar yield. The key to success was use of palladium bromide and copper bromide instead of chloride analogues.

By oxidative addition of a carbon-halogen bond

The direct oxidative addition of vinyl or aryl halides directly affords the desired Csp2-M bond. This method is the most widely used, although it requires pre-activated substrates. The efficiency of this method is clearly illustrated by the carbonylative version of the classical palladium-catalyzed cross-coupling reactions. For example, the carbonylative Sonogashira reaction has been described as early as 1981 by Tanaka (Scheme 28).49 The reaction occurred in an amine solvent and under harsh conditions (120 °C and 20 atm of carbon monoxide). However, the scope of the reaction is broad and even alkenyl bromides are suitable substrates for the reaction. The electronic effects of the substituents on the aromatic group have little effect on the yield of the reaction. Indeed, both electron-donating and withdrawing groups led to the desired products in equally good yields.

3 carbonylation of  hybridized carbon atoms

As briefly described, palladium-catalyzed carbonylation reactions of Csp2 centers has been extensively studied. To the contrary, such carbonylation reactions involving Csp3 centers are rather scarce. Two main factors may explain this matter of fact: the possibility of β-hydride elimination and the difficulty of oxidative addition of Csp3-X bonds to palladium.

Carbonylation of π-allyl systems

Carbon monoxide coordination to the Pd atom of an η3-allyl complex can in principle either trigger reductive elimination to generate the organic allyl-X and Pd(0) (Scheme 45, right) or insert into the allyl moiety to promote a successive nucleocarbonylation, if an appropriate nucleophile is present (Scheme 45, left).

Table of contents :

General Introduction
CHAPTER I : Transition metal catalyzed domino reactions
Pure domino reactions (TM-DOM)
Pseudo-domino reactions (TM-PDOM)
i. Pseudo-domino type I reactions
ii. Pseudo-domino type II reactions
CHAPTER II : Carbonylation reactions
Carbonylation of sp-hybridized carbon atoms
Carbonylation of sp2-hybridized carbon atoms
i. Starting from an alkyne substrate
ii. By oxidative addition of a carbon-halogen bond
1) Cross-coupling reaction
2) Alkoxycarbonylation
3) Aminocarbonylation
4) Carboxylic acids formation
iii. By C-H activation
Carbonylation of sp3 hybridized carbon atoms
i. Carbonylation of π-allyl systems
1) Via carbopalladation
2) Via hydropalladation
iii. Case of benzyl halides
iv. With α-carbon-bound resonance stabilized electron withdrawing groups
1) Carbonylation of α-haloacetates
2) Carbonylation of α-haloketones
Carbonylation within domino reactions
CHAPTER III : Decarboxylative Allylation
Catalysis by the transition metals
Decarboxylative allylation with other electron withdrawing groups
Results and Discussion
CHAPTER IV : Execution of the project
Development of new Pd-catalyzed domino sequences involving carbon a)monoxide
The requirement of a sequential study
i. Trials at atmospheric pressure
ii. Carbonylation of α-chloroketones
iii. Decarboxylative allylation
i. Preliminary results
ii. Pressure
iii. Catalyst loading
iv. Used of a co-solvent and influence of the base
v. Screening of ligands
Scope and limitation of the pseudo-domino sequence
i. Functionalization of α-chloroketones
1) Substitution on the aromatic ring
2) Substitution of the chloroketone at the α-position
ii. Substituted allylic alcohols
Mechanistic studies of the pseudo-domino sequence
i. Oxidative addition at room temperature
ii. Kinetic studies
iii. Study of the C-Pd / O-Pd equilibrium
Conclusion and perspectives
CHAPTER V : Toward a new domino sequence
Sequential study with incrementation of the domino sequence
i. Synthesis of the cyclization precursor
ii. Study of the cyclization, trapping with a hydride
iii. Toward a new pseudo-domino type I sequence: « N-allylation / carbopalladation / hydride trapping»
iv. Toward a new triple pseudo-domino type I sequence: «N-allylation / carbopalladation / methoxycarbonylation»
1) With formation of a neopentyl palladium intermediate .
2) Study of the competition between the β-hydride elimination and carbonylation
v. Approaches toward the full pseudo-domino sequence
1) Toward the full sequence « N-allylation / carbopalladation / carbonylative / decarboxylative allylation »
2) Switch from allyloxy- to methoxycarbonylation
3) Possible pathways from 34 to 23
vi. Extension to different groups than malonate
1) Planning intermediate β-ketoesters
2) Planning intermediate malononitriles
vii. Approach to a triple pseudo-domino type I sequence: « N-propargylation / 5-exo-dig carbopalladation / carbonylation »
1) Methoxycarbonylation
2) Allyloxycarbonylation
Conclusion and perspectives
General conclusion
Experimental Section
General instrumentation:
General procedures (GP)

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