Reissert compounds rearrangements

Apart from isolated reports summarized in Scheme 47, the chemistry of the fully conjugated ring systems has not been especially developed since CHEC-II(1996). In 1999, Monnier et al. reported the 1,3-dipolar cycloaddition of Reissert compound 160 with acrylates. Addition of triethylamine traps hydrofluoroboric acid and increases the proportion of milnchnone imine 160B the reaction therefore predominantly yields 1,3-adduct 161 which rearranges to 162 (Scheme 47) <1996BSB777, 1999EJ0297>. 

Isoquinoline Reissert compounds of type 12 could be easily converted to the corresponding 1-cyanoisoquinolines (13) by simple base treatment (4,5) (Scheme 3). This transformation also takes place with high yields when type 12 compounds are oxidized with molecular oxygen in a two-phase system in the presence of phase-transfer catalysts (12-14). It should be mentioned that similar oxidation of dihydro Reissert compounds of type 14 afforded the corresponding dihydroisocarbostyril derivatives (15) (12-14). Base treatment of isoquinoline Reissert eompounds followed by intramolecular rearrangement, due to the absence of a proper intermolecular reaction partner, results in 1-acylisoquinoline derivatives (18) (3). 

A reinvestigation of the experiments on the UV irradiation of l-acetyl-l,2-dihydroquinoline-2-carbonitriles (Reissert compounds) 561 unequivocally demonstrated that the rearrangement via the diradical intermediate 562 gave 4//-3,l-benzoxazines 563 and 565 rather than the benzazete derivatives described earlier. The yields and the type of products were strongly influenced by the substituent R at position 4 while irradiation of the unsubstituted quinoline 561 (R=H) gave 3,1-benzoxazine 563 in nearly quantitative yield, the amount of the corresponding methyl-substituted analog 565 that could be isolated was considerable lower, due to its irreversible isomerization via 562 to the stable cycloprop[/ ]indole derivative 564 (Scheme 107) <199811(49)121 >. 

This section deals with transformations of heterocyclic rings and includes not only addition of carbenes and nitrenes, but also rearrangements frequently following these additions. Also included are topics such as the synthesis of Reissert compounds as well as miscellaneous oxidations and reductions. 

A number of alkylation reactions, Michael-type additions, and base-catalyzed rearrangements have been previously reported for Reissert compounds. These reactions appear to proceed through the conjugate... 

Pyridazine or 3-methylpyridazine with trimethylsilyl cyanide and benzoyl cyanide gave Reissert compound 106, which is easily rearranged into 107. In addition, compound 108 is formed, resulting from the reaction of one mole of cyanide and three moles of benzoyl chloride (81JHC443 ... 

The anion 10, generated from the reaction of 3-benzoyl-3,4-dihydro-2-methylquinazoline-4-carbonitrile (a 2-methylquinazoline Reissert compound) with sodium hydride, undergoes both rearrangement and aromatization (cf. p 84), resulting in the formation of 4-benzoyl-2-methylquinazoline (32%), and 2-methylquinazoline-4-carbonitrile (20%). ... 

A variety of isoquinoline Reissert compounds (2) have been caused to undergo rearrangement of the acyl group from nitrogen to carbon by treatment with sodium hydride in dimethylformamide to give ketones of type similar manner, the bis-Reissert compound 14... 

Attempted rearrangement of 4-chloro-2-(4-methoxybenzoyl)dihydro-isoquinaldonitrile with sodium hydride in dimethylformamide led to a product whose structure was 59 or 60. Treatment of the 8-benzoyloxy-Reissert compound 61 with sodium hydride in dimethylformamide resulted in attack of the anion at the ester rather than the amide carbonyl to give 62. ... 

Reaction of the Reissert compound of 4-methylquinoline with sodium hydride in dimethylformamide and acrylonitrile at 0° led to rearrangement to 4-methyl-2-benzoylquinoline, while reaction at — 30° led to 67a and 676. Use of sodium amide-liquid ammonia gave an improve yield of 67a and 67b. Reaction of 3 with potassium t-butoxide in dimethyl sulfoxide and acrylonitrile gave 67c. ... 

The addition of hypochlorous acid to the 3,4-position of the isoquinoline Reissert compound (2 R = Ph) takes place to give the chlorohydrin 71." Use of A -chlorosuccinimide in ethanolic dioxane gave the 0-ethyl derivative. Various reactions of the chlorohydrin led to isochromenes and a rearranged isoquinoline." ... 

A number of other miscellaneous systems that bear some relationship to Reissert compounds have also been reported but will not be covered in depth here. Thus, for example, the reaction of isoquinoline, potassium cyanide, and alkyl chloromethyl ethers give 116. A similar compound was also prepared from quinoline. Compounds of type 117 have been reported to undergo rearrangements similar to Reissert compounds. A... 

A number of synthetically useful transformations have been carried out with the Reissert compound 15 (Popp 1967 [114]). Strong bases bring about deprotonation to give the anion 16, which rearranges to 1-benzoylisoquinoline 17 after loss of cyanide and a 1,2-acyl shift. Electrophilic reagents, e.g. alkyl... 

The condensation of aromatic aldehydes with the anion of an iV-benzoyl Reissert compound is known to proceed through an intramolecular rearrangement to give esters of type 1. It has now been shown that condensation of the anion of the //-acetyl Reissert compound 2 with 2-nitrobenzaldehyde proceeds in a different manner to afford the derivative 3, the by-product being iso-quinoline. ... 

Stamegna and McEwen noted the presence of minor products such as a-benzamidostilbenes from the Stevens rearrangement of analogs of Reissert compounds. These minor products could be formed by recombination of radicals formed by homolysis. Further evidence for this was provided in that the minor products were observed for radical intermediates one would predict to be relatively stable (such as benzyl radicals), yet they were not observed if the radical intermediate was not expected to be stable (such as aryl radicals). 

Cyclic Reissert equivalent compound 265 yields, by transformation into intermediate 266 followed by sulfuryl chloride-mediated ring-opening rearrangement, L-type homoberbine enamide 267 (05T5037). 

In summary, it appears that Reissert salts undergo 1,3-dipoIar addition reactions with reactive acetylenic 1,3-dipolarophiles to give compounds of type 24 and undergo complex condensation-rearrangement reactions with olefinic dienophiles to give products of the type 25. 

Abstract The use of organoaluminum-based Lewis acids (A1R X3 R = alkyl, alkynyl, X = halide or pseudohalide) in the period 2000 to mid-2011 is overviewed with a focus on (1) stoichiometric reactions in which one of the organoaluminum substituents is transferred to the substrate (e.g., the opening of epoxides, 1,2-additions to carbonyl compounds, coupling with C-X, and Reissert chemistry) and (2) asymmetric, often catalytic, reactions promoted by Lewis acid catalysts derived from organoaluminum species (e.g., use of auxiliaries with alanes, Diels-Alder, and related cycloaddition reactions, additions to aldehydes and ketones, and skeletal rearrangement reactions). 

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