Aiylation

Scheme 21.4 Intermediates formed during the aiylation of acrolein ethylene acetal.

Electrochemical aiylation of activate alkenes can be carried out using a nickel catalyst in which the low valency state is stabilised by a pyridine ligand. Under these conditions, the alkenc is also involved in coordination to nickel. Tliere is no... 

The double N-aiylation of the 6-aminocarbazole 1082 with the dibromobiphenyl derivative 1075 under Buchwald-Hartwig N-arylation conditions afforded N-SEM-murrastifoline-A (1083) in 58% yield. Finally, the M-SEM group was removed under acidic conditions to furnish murrastifoline-A (186) in 94% yield (666,667) (Scheme 5.174). 

For alkylation or aiylation by alkyl/ aryl halides or sulfonates, see page 779, Section 4. 

It is reported that the palladium-catalysed intramolecular aromatization of 1,1 -dichloro-9/T-fluoren-9-yIidene (15) may lead to the formation of fullerene fragments.89 The amiulation reaction, under palladium catalysis, between iodoanflines and ketones may yield indole derivatives.90 There have also been studies of the palladium-catalysed carbonylation of o-iodophenols with allenes which may lead to l-benzopyran-4-one derivatives,91 of the intramolecular coupling of phenols with aryl halides,92 and of the intramolecular Heck aiylation of cyclic enamides.93... 

Cupric chloride, if present in concentrations above ca. 0.5 M, may cause side reactions to occur in the olefin aiylation reaction similar to those that occur with cupric chloride in the vinyl acetate synthesis mentioned above. The side reaction produces 2-arylethyl chlorides and these products may be made the major ones if cupric chloride is present to the extent of about 2M in 10% aqueous acetic acid solution 29>. The mixed solvent is required to obtain the necessary solubility of the cupric chloride. This is a general reaction useful for producing a variety of 2-arylalkyl halides. For example, 3-phenyl-2-chloropropionaldehyde is obtained in 63% yield by the reaction of phenylpalladium chloride , cupric chloride and acrolein. 

Alkenylation and Aiylation of Grignard Compounds (Kumada Coupling)... 

Aiylation with a homocuprate. A key step in a synthesis of the cannabis constituent 4 is the reaction of 1 with the homocuprate derived from olivetol dimethyl ether (2) hy regiospecific lithiation followed by reaction with CuBr. The cuprate does not react with 1 in the absence of a Lewis acid, but in the presence of BF, etherate (3.5 equiv.) ( —)-3 is obtained in 78% yield with high regio- and stereospecificity. The dihydrobromide of... 

Aiylation, of benzene, 49, 44 Arylbenzenes, preparation by free radical arylation, 49, 44... 

In the last years several publications appeared describing palladium-catalyzed a-arylations of ketone enolates for the synthesis of a-aryl ketones, involving ketone eno-lates, silyl enol ethers and intramolecular a-aiylation of ketone enolates . In this process, an enolate is generated from a ketone in the presence of an aryl halide, and a palladium catalyst couples this enolate with the aryl halide. Iwama and Rawal proposed... 

TvBLE 9, Tyjpm of Aryl HaUilas tbed in the Aiylation of Ajtiridiiiei... 

FUJI WAR A Lanthanide (Yb) reaction 136 FUJIWARA Aiylation, caiboxylation 137 FUJIWARA - HECK Coupling 138... 

For an interesting application of a cyclopropanolate as a homoenolate in a Heck-type aiylation see F. A. Khan, R. Czerwonka, H.-U. Reissig, Synlett 1996, 533-535. 

Until recently, a-substitution of carbonyl compounds was largely restricted to those cases where alkyl groups, such as Me, allyl, and benzyl, were introduced via classical enolate alkylation. a-Aiylation of ketones with aryl halides can be effected using K in NH3 [120-123]. However, this reaction does not appear to be satisfactory for selective -alkenylation and a-alkynylation. -Arylation of ketones has also been catalyzed by Ni [124] and Pd [125,126]. The Pd-catalyzed version employed enolstannanes. This reaction has also been applied to a-alkenylation [127]. However, these reactions appear to be of very limited scope. Thus, the Pd-catalyzed procedures appear to be satisfactory mainly for a-substitution of methyl ketones. Furthermore, none of them addresses the critical question of how to control the regiochemistry of c-substitution, i.e., a vs. a. Critically needed from the viewpoint of selective synthesis were... 

Cyclic imines, such as 1-pyrroline (6) and A -piperidine (32), which are prone to trimerization, can be prepared from iV-halopyirolidine and iV-halopiperidine respectively and treated in situ with organoli-thium reagents to provide 2-alkylated and 2-aiylated pyrrolidines and piperidines in modest yield. Corey et al. treated substituted piperidine (17) generated in this fashion with iV-pentyllithium to establish die stereochemistry of the remote pentyl side chain of perhydrohistrionicotoxin (33), as condensation occurred from the more accessible re-face of the imine ir-system of (17). 

SCHEME 9. Anionic 0-donors screened for W-aiylation of primary alkyl amines... 

Unlike other diene photopericyclic reactions, cyclohexadiene ring opening proceeds with reasonable efficiency in phenyl-substituted derivatives, although the quantum yields are generally significantly lower than those of non-aiylated systems. Two examples of the conversion of 93 to 94 are shown in equation 36 d79... 

The observation of a competition between the pathways followed by the 10-1-3 intermediates in the aiylation reactions with diaiyliodonium salts led Moriarty to consider whether the ligand coupling was taking place by a concerted mechanism (path a) or with the intervention of radical species (path b) 21 (Scheme 2.28)... 

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