Nucleophilic substitution—continued selectivity

Additions to quinoline derivatives also continued to be reported last year. Chiral dihydroquinoline-2-nitriles 55 were prepared in up to 91% ee via a catalytic, asymmetric Reissert-type reaction promoted by a Lewis acid-Lewis base bifunctional catalyst. The dihydroquinoline-2-nitrile derivatives can be converted to tetrahydroquinoline-2-carboxylates without any loss of enantiomeric purity <00JA6327>. In addition the cyanomethyl group was introduced selectively at the C2-position of quinoline derivatives by reaction of trimethylsilylacetonitrile with quinolinium methiodides in the presence of CsF <00JOC907>. The reaction of quinolylmethyl and l-(quinolyl)ethylacetates with dimethylmalonate anion in the presence of Pd(0) was reported. Products of nucleophilic substitution and elimination and reduction products were obtained . Pyridoquinolines were prepared in one step from quinolines and 6-substituted quinolines under Friedel-Crafts conditions <00JCS(P1)2898>. 

Nucleophilic substitution reactions are highly important in organic synthesis. By conducting these within continuous flow reactors, it is observed that the products are generated in higher yield and selectively compared to the corresponding batch reactions. It is evident from the literature examples cited in this chapter that the reactions can be easily scaled within commercial micro reactor systems to enable kg quantities of product to be readily produced. 

The more substituted radicals continue to be measurably the more nucleophilic. The relative rates with which the various alkyl radicals react with the 4-cyan-opyridinium cation (7.33, Y = CN) and the 4-methoxypyridinium cation (7.33, Y = OMe) are given in Table 7.2. The LUMO of the former will obviously be lower than that of the latter. The most selective radical is the ferf-butyl, which reacts 350000 times more rapidly with the cyano compound than with the methoxy. This is because the ferf-butyl radical has the highest-energy SOMO, which interacts (B in Fig. 7.4) very well with the LUMO of the 4-cyanopyridi-nium ion, and not nearly so well (A) with the LUMO of the 4-methoxypyridinium ion. At the other end of the scale, the methyl radical has the lowest-energy SOMO, and hence the difference between the interactions C and D in Fig. 7.4 is not so great as for the corresponding interactions (A and B) of the ferf-butyl radical. Therefore, it is the least selective radical, reacting only 50 times more rapidly with the cyano compound than with the methoxy. 

Development of the chemistry of the salt (156) continues. When converted into the alkoxyphosphonium salts (157) and treated with, e.g., methyl-lithium or lithium dimethylcuprate, alkylation at the alkoxy carbon to form R—Me derivatives only occurs to a small extent, due to competition from the strongly nucleophilic N-methylanilide ion. However, alkylation (and arylation) at the alkoxy carbon has been achieved by the reaction of the salt (156) with mixed cuprates derived from an allylic alcohol, copper(i) iodide, and an organolithium reagent, enabling direct substitution of the hydroxy-group of allyl alcohols by alkyl or phenyl groups in a regio- and stereo-selective manner. ... 

J. D. Cotton has continued with his thorough studies on the fundamental factors that govern the rates of insertion of CO into metal-alkyl bonds. The reaction of [RMn(CO)5] (R = substituted PhCH2 groups) with a selection of P-donor nucleophiles occurs in MeCN(S) according to the mechanism shown in Eq. (28), where the product is usually the cis-isomer.< The rate equation... 

---