Nucleophilic ring closure

The Friedel-Crafts reaction, which proceeds via electrophilic aromatic substitution, as illustrated in the following scheme, is unique to the manufacture of anthanthrone pigments. Most other polycyclic anthraquinone pigments are synthesized via nucleophilic ring closure. 

A-Benzylimines have also been reported to react with acrylonitriles under solidrliquid conditions in which the initial anionic intermediate undeigoes an intramolecular nucleophilic ring closure to produce a diastereoisomeric mixture of the pyrrolidine (Scheme 6.23) [30-32], Similar cyclized products have been reported for the reaction of benzylidene-protected a-amino esters and vinyl ketones [33, 34],... 

The formation of cyclopropanes from 7C-deficient alkenes via an initial Michael-type reaction followed by nucleophilic ring closure of the intermediate anion (Scheme 6.26, see also Section 7.3), is catalysed by the addition of quaternary ammonium phase-transfer catalysts [46,47] which affect the stereochemistry of the ring closure (see Chapter 12). For example, equal amounts of (4) and (5) (X1, X2 = CN) are produced in the presence of benzyltriethylammonium chloride, whereas compound (4) predominates in the absence of the catalyst. In contrast, a,p-unsatu-rated ketones or esters and a-chloroacetic esters [e.g. 48] produce the cyclopropanes (6) (Scheme 6.27) stereoselectively under phase-transfer catalysed conditions and in the absence of the catalyst. Phenyl vinyl sulphone reacts with a-chloroacetonitriles to give the non-cyclized Michael adducts (80%) to the almost complete exclusion of the cyclopropanes. 

Polyfluorophenylacetaldehydes show a novel nucleophilic ring closure reaction pentafluorophenylacetaldehyde, treated with sodium hydride in DMF, gives 4,5,6,7-tetrafluorobenzofuran (123, R = H) (13% yield). Under the same conditions, 2-pentafluorophenylaceto-phenone gives the 2-phenyl derivative (123, R = Ph) (76% yield).323... 

Synthetic access to quinidine positions other than C2 and C3 is more challenging. Treatment of quinine in superacid, for example, delivers a tricyclic derivative 96 via nucleophilic ring closure between the C9 OH oxygen and a carbocation at C5 (Scheme 12.27). However, cyclization occurs only subsequent to a rearrangement of the azabicyclo[2.2.2]octane unit into a thermodynamically more stable [3.2.1]-system [65]. 

When a carbon suboxide molecule reacts with two sites of comparable nucleophilicity, ring closure can take place if a favorable mutual spatial orientation of the four reaction centers prevails. For example, carbon suboxide can react with N-aryl-substituted benzamidines to give six-membered ring products quantitatively (38) ... 

Alcohols with a good leaving group in the y-position can be cyclized into oxetanes. This approach was successfully applied to the synthesis of fluorinated oxetanes either by electrophilic cyclization of 2-perfluoroalkyl 1,3-diols in concentrated sulfuric acid or by nucleophilic ring closure of fluorinated y-chloro" or y-fluoro alcohols under action of a strong base (see Scheme 2.2). The ease of intramolecular cyclization is influenced by the nucleophilicity of alkoxy group and the best yields are obtained for tertiary alcohols. 

Parham, W. E., Jones, L. D. and Sayed, Y. 1975. Four- to seven-membered ring annulation of aryl bromides bearing ortho side chains having an electrophilic moiety, accomplished by halogen-metal exchange and subsequent nucleophilic ring closure. J. Org. Chem. 40 2394-2399. 

Intramolecular nucleophilic ring closure at pyridine o-position... 

Nucleophilic ring-closure by attack of the C=S function on the allenic sp carbon (presumably via an isothiourea intermediate) leads to the exomefhylene 4,5-dihydrothiazole... 

Nucleophilic ring closure with cyclimmonium salts l,9a-Dihydro-4H-pyrido[2,l-c][l,2,4]triazines... 

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