Some reactions of alkyl aryl ketones

Some reactions of alkyl aryl ketones (Expts 6.146 to 6.148). 

Optical detection of intermediates produced in the reactions of triplet carbonyl compounds with electron donors has some obvious limitations. However, the technique of CIDNP is proving particularly effective at elucidating the reaction pathways in these systems. The outstanding work of Hendriks et al. (1979) illustrates the power of the technique. Not only was the role of radical ions in the reactions of alkyl aryl ketones with aromatic amines defined but the rate constants for many of the processes determined. The technique has been used to show that trifluoracetyl benzene reacts with electron donors such as 1,4-diazabicyclo[2.2.2]octane and 1,4-dimethoxy-benzene by an electron-transfer process (Thomas et al., 1977 Schilling et al., 1977). Chemically induced dynamic electron polarisation (CIDEP) has been... 

Rate constants and Arrhenius parameters for the reaction of Et3Si radicals with various carbonyl compounds are available. Some data are collected in Table 5.2 [49]. The ease of addition of EtsSi radicals was found to decrease in the order 1,4-benzoquinone > cyclic diaryl ketones, benzaldehyde, benzil, perfluoro propionic anhydride > benzophenone alkyl aryl ketone, alkyl aldehyde > oxalate > benzoate, trifluoroacetate, anhydride > cyclic dialkyl ketone > acyclic dialkyl ketone > formate > acetate [49,50]. This order of reactivity was rationalized in terms of bond energy differences, stabilization of the radical formed, polar effects, and steric factors. Thus, a phenyl or acyl group adjacent to the carbonyl will stabilize the radical adduct whereas a perfluoroalkyl or acyloxy group next to the carbonyl moiety will enhance the contribution given by the canonical structure with a charge separation to the transition state (Equation 5.24). 

Over the last five years, we have designed, synthesized, and applied new ligands for asymmetric 1,2- and 1,4-addition reactions. Suitable ligands were found for the addition of alkyl-, aryl-, and alkenylzinc reagents to a,(3-unsaturated aldehydes and ketones, a-branched and unbranched aliphatic aldehydes, and imines. Although some substrates such as ketones and other carbonyl compounds have remained a challenge, we believe that this system provides an excellent entry into various classes of chiral intermediates. Application of these synthesized complex molecules is the current pursuit in our laboratories. 

Asymmetric induction has also been evaluated in the reaction of a-aryl substituted ketones, esters, and lactones (43). The potential of the method is demonstrated by the synthesis of some naturally occurring or nonnaturally occuring chiral compounds (Scheme 15). Similarly, asymmetric synthesis of ( — )-physostigmine, a clinically useful anticholinesterase agent, is accomplished by using phase-transfer alkylation of... 

The reaction of an aryl and an alkyl iodide in presence of complex (103) and the Zn-Cu couple leads to alkyl aryl ketones in good yields (equation 115).492 By-products such as ArR, ArH and Ar2 were found in some cases. Replacement of alkyl iodides by benzyl chlorides gave benzyl ketones, but the formation of by-products due to coupling reactions was significant. Dialkylzinc complexes were formed here and the proposed mechanism is given in Scheme 41. 

Among common carbon-carbon bond formation reactions involving carbanionic species, the nucleophilic substitution of alkyl halides with active methylene compounds in the presence of a base, e. g., malonic and acetoacetic ester syntheses, is one of the most well documented important methods in organic synthesis. Ketone enolates and protected ones such as vinyl silyl ethers are also versatile nucleophiles for the reaction with various electrophiles including alkyl halides. On the other hand, for the reaction of aryl halides with such nucleophiles to proceed, photostimulation or addition of transition metal catalysts or promoters is usually required, unless the halides are activated by strong electron-withdrawing substituents [7]. Of the metal species, palladium has proved to be especially useful, while copper may also be used in some reactions [81. Thus, aryl halides can react with a variety of substrates having acidic C-H bonds under palladium catalysis. 

A study on the scope of the reaction applied to different types of carbonyl compounds (aldehydes, cyclic ketones and some substituted alkyl aryl ketones ) has been published. Two different secondary amines (pyrrolidine, morpholine) were used. Titanium tetrachloride on various supports (e.g. AljOj) acted as effective dehydrating agents for the preparation of enamines from hindered ketones and secondary amines . 

In these reactions, the cydization mode is also determined by the substitution patterns of the aryl ring. If one or both ortho-positions are occupied by a methoxy group, the reaction affords spiro-endo mode cydization products 411 (Scheme 10.159) [185]. The formation of a 408-type intermediate was supported by the fact that 2-halo-l-alkyl ketones 412 were formed in some cases [184, 185]. 

The alkyl halide must be one that is reactive toward SN2 displacement. Alkyltriphenylphosphonium halides are only weakly acidic, and strong bases must be used for deprotonation. These include organolithium reagents, the sodium salt of dimethyl sulfoxide, amide ion, or substituted amide anions such as hexamethyldisilylamide (HMDS). The ylides are not normally isolated so the reaction is carried out either with the carbonyl compound present or it may be added immediately after ylide formation. Ylides with nonpolar substituents, for example, H, alkyl, or aryl, are quite reactive toward both ketones and aldehydes. Scheme 2.16 gives some examples of Wittig reactions. 

---