Quinoline bases, acylation

The homolytic acylation of protonated heteroaromatic bases is, as with alkylation, characterized by high selectivity. Only the positions a and y to the heterocyclic nitrogen are attacked. Attack in the position or in the benzene ring of polynuclear heteroaromatics has never been observed, even after careful GLC analysis of the reaction products. Quinoline is attacked only in positions 2 and 4 the ratio 4-acyl- to 2-acylquinoline was 1.3 with the acetyl radical from acetaldehyde, 1.7 with the acetyl radical from pyruvic acid, and 2.8 with the benzoyl radical from benzaldehyde. 

Bennasar et al. reported a new radical-based route for the synthesis of calothrixin B (378) (869). This synthesis starts from the 2,3-disubstituted N-Boc indole 1558 and uses a regioselective intramolecular acylation of a quinoline ring as the key step for the construction of the calothrixin pentacyclic framework. Chemoselective reaction of in s/fM-generated 3-lithio-2-bromoquinoline [from 2-bromoquinoline 1559 with LDA] with the 3-formylindole 1558 followed by triethylsilane reduction of the... 

Reissert compounds (l-acyl-l,2-dihydro-2-quinolinecarbonitriles) have been prepared on cross-linked polystyrene and C-alkylated in the presence of strong bases (Entry 8, Table 15.25). Treatment of polystyrene-bound C-alkylated Reissert compounds with KOH leads to the release of isoquinolines into solution (Entry 9, Table 15.25). The reaction of support-bound quinoline- and isoquinoline /Y-oxides with acy-lating agents followed by treatment with electron-rich heteroarenes and enamines has been used to prepare alkylated and arylated derivatives of these heterocycles (Entry 10, Table 15.25 see also Table 15.26). 

Reaction CXII. Action of certain Bases on Acyl Chlorides. (B., 34, 2070 J. pr., [2], 50, 479.)—When pyridine or quinoline act on an acid chloride, and the addition product which is formed treated with water, the acid anhydride is obtained (cf. Reaction CIX.). 

A new process for the homolytic acylation of protonated heteroaromatic bases has been developed by Minisci et al. An A-oxyl radical generated from iV-hydroxyphthalimide by oxygen and Co(ll) abstracts a hydrogen atom from an aldehyde. The resulting nucleophilic acyl radical adds to the heterocycle which is then rearomatized via a chain process. Under these conditions, quinoline and benzaldehyde afford three products (Equation 108) <2003JHC325>. A similar reaction with 4-cyanopyridine gives 2-benzoyl-4-cyanopyridine in 96% yield. 

This catalyst was also applicable in the Strecker reaction of ketiinines including quinoline and isoquinoline (Scheme 6.112) [139]. Acid chlorides were combined for use in making iminium cations to enhance the reactivity of this class of poorly electrophihc substrate. Thus the reaction involves dual activation of the acyl quinolium or isoquinolinium ion and MejSiCN by the Lewis acid (Al) and the Lewis base (oxygen atom of phosphor oxide) of 93, respectively. The reaction proceeded with moderate to high enantioselectivity. 

Quinoline, Isoquinoline, and their Benzo- and Hydro-derivatives. - Relatively few syntheses of quinolines are based on 2,3-disubstituted pyridines a recent addition to their number is illustrated in Scheme 33. The essential steps are Michael addition, intramolecular acylation, and aromatization via loss of toluene-p-sulphenic acid. ... 

One routine method for the functionalization of quinolines is the addition of substituents to the 2-position. Further advances in the catalytic, enantioselcctive Reissert-type reaction were reported. Quinoline 63 was treated with 2-furoyl chloride and TMSCN in the presence of Lewis acid-Lewis base bifunctional catalyst 64 followed by reduction of the corresponding enamine to afford quinoline 65 in 93% ee. Quinoline 65 was subsequently converted to (-)-L-689,560, a potent NMDA receptor antagonist <01JA6801>. Additions of ally.silanes to quinolines acylated with chloroformate esters and catalyzed by various triflate salts were reported <01T109>. 

The first syntheses of the homoerythrinane framework are following the assumed hiosynthetic route. Thus, the N-protected 1-phenethyliso-quinoline 196 (Scheme 35) can be cyclized by a phenol oxidative procedure providing the tetracyclic naphthalenoisoquinoline 197, a homologue of neoproaporphine (35) in 35-45% yield (105). This has been transformed to the dibenzazecine intermediate 198 by ring reopening. Finally, the N-deprotected free amine base can be oxidized giving homoerysodienone (199) (106, 107). A diphenoquinone type intermediate 38 (Scheme 1 n = 2) is not available from the N-acylated base 198. 

Generally, the use of other heterocycles besides quinoline would be considered modifications of the original Reissert protocol. This reaction has been extended to convert an acyl chloride into an aldehyde through a one-pot process by adding the acyl chloride to a solution of quinoline and hydrocyanic acid, and subsequent steam distillation of the entire mixture with sulfuric acid. In addition, the formation of the Reissert compound has been modified to occur enantioselectively using TMSCN as the nucleophilic species in the presence of a Lewis acid-Lewis base bifunctional catalyst. Moreover, tri-n-butyltin cyanide and acetone cyanohydrin are also used for the preparation of the Reissert compounds. 

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