Quinoline synthesis 568 Subject

The specific ortho functionalization of arylamines is obviously important in quinoline synthesis (cf. the rc-allyl procedure devised for the preparation of o-allylanilines used as indole and quinoline precursors).76 Recently acetanilides have been subjected to orthopalladation and the ensuing complexes converted into useful precursors of 2-substituted quinoline derivatives (Scheme 143).215... 

The Skraup reaction is of wide scope for the synthesis of substituted quinolines. Certain primary amines, bearing a cyano, acetyl or methyl group, may however be subject to decomposition under the usual reaction conditions. 

The use of solid supported, recyclable catalysts, is a well-assessed technique in classic organic chemistry, and many exhaustive reviews dealing with this subject are available [105, 115]. The use of solid supported catalysts for library synthesis in solution has also been reported. Among others, Kobayashi et al. presented the use of a new supported scandium catalyst for 3CC reactions leading to solution libraries of amino ketones, esters, and nitriles (24-member model discrete library) [116], or to quinolines (15-member model discrete library) [117], and Jang [118] presented a polymer bound Pd-catalyzed Suzuki coupling of organoboron compounds with halides and triflates. This area was also briefly reviewed recently [119]. 

Isatin (lH-indole-2,3-dione) is a synthetically versatile substrate, where it can be used for the synthesis of a large variety of heterocyclic compounds, such as indoles and quinolines, and as a raw material for drug synthesis. Isatin has also been found in mammalian tissues, and its function as a modulator of biochemical processes has been the subject of several discussions. The advances in the use of isatin for organic synthesis during the last twenty-five years, as well as a survey of its biological and pharmacological properties are reported in this review and in the accompanying supplementary information. 

Shamma s synthesis (Scheme 29) leaves the formation of the quinoline ring to a late stage, building up a tricyclic pyridone-ketone (121) which is then subjected to a Friedlander quinoline ring synthesis. 

Myriad examples are known of oxindoles reacting to form indoles without prior carbonyl activation. Given (he vast scope of this subject, only a few early examples will be cited in addition to recent studies. Several groups have annulated oxindoles to access fused-indole heterocycles. Ila, Junjappa, and coworkers prepared pyrido[2,3-( ]indoles [61, 62] and 67/-indolo[2,3-fc]quinolines [63] using this approach (Scheme 9, equation 1). Adib and colleagues reported a simple synthesis of 9/7-pyrimido[4,5-Z ]indoles from oxindoles (eqnation 2) [64], and Bazgir and coworkers described a four-component one-pot a-carboUne synthesis... 

An example of the synthesis of a benzo-fused pyridine (i.e., a quinoline), containing an embedded ferrocene unit shown in structure 187, has been reported by Mamane and Fort [62], Commencing with the bisaldehyde 188 and subjecting it to a Wittig one-carbon homologation at each aldehyde group, it was converted into the bisvinyl complex 189, setting this up for an aUcene RCM reaction to... 

Very recently, Yu and co-workers reported a one-pot synthesis of phenan-thridines and quinolines (63) from commercially available or easily prepared aldehydes (61) (Scheme 7.42) [112]. The acyl oximes were obtained in sim from aldehydes and hydroxylamine in the presence of p-Cl-benzenesulfonic acid (CBSA) as an additive. Then acyl oximes were subjected to visible-hght photoredox catalyzed cycUzation via an iminyl radical to furnish azaarene products in moderate to good yields. 

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