Reissert reaction chloroformate

The Ugi-Reissert reaction is quite general [188] it accepts a wide array of isocyanides, azines (excluding pyridine and derivatives lacking unsubstituted a-positions) and activating agents (chloroformates, acid chlorides, anhydrides. 

A solid-phase Ugi-Reissert reaction on chloroformate resin, has been reported. The product, the ot-carbamoylated isoquinoline 230, is released by oxidative cleavage (Scheme 33a). Interestingly, the enamide moiety in the adduct can be exploited to perform this process in tandem with a Povarov MCR [189, 190]. In this way, by interaction of dihydroisoquinoline 231 with aldehydes, anilines and a suitable Lewis acid catalyst, the polyheterocyclic system 232 was prepared (Scheme 33b). The Zhu group devised an innovative approach for the synthesis of this class of compounds. They employed the heterocyclic amine 233, which was oxidized in situ to the dihydroisoquinoline 234 with IBX, to undergo the classic Ugi reaction. Remarkably, all the components are chemically compatible, allowing the sequence to proceed as a true MCR (Scheme 33c) [191]. 

Ethinylation of quinohne by reaction with terminal alkynes and chloroformates in the presence of DIPEA and Cul proceeds in analogy to the Reissert reaction [94, 158], QuinoUne-N-oxide reacts with KCN/benzoyl chloride to afford 2-cyanoquinoline (23) ... 

Disubstituted pyrido[3,4- ]pytazines 90 were reacted with equivalent amounts of trimethylsilyl cyanide and acyl chlorides or chloroformates in the presence of a catalytic amount of AICI3 in CH2CI2 to give the Reissert compounds 91, where the reactions occurred across the C-5,N-6 bond <1994JHC819>. On the other hand, treatment of 90 (R = = Ph) with benzenesulfonyl chloride and trimethylsilyl cyanide in the presence of a catalytic amount of... 

If the Reissert compound from the reaction with ethyl chloroformate (224) is lithiated at C-2 and subsequently treated with benzaldehyde, the final product is the l//-oxazolo[3,4-a]quinolin-l-one (225) (73JHC99). 

Sequential reaction of azines with alkyl hthium compounds and chloroformates usually affords the expected Reissert-type products 136, together with minor amounts of doubly acylated compounds 135 (Scheme 18b). Isoquinoline is likely to react directly with the alkyl-lithium compound to generate the alkylated lithio-enamine intermediate E, and this species may account for the formation of dihydroisoquinolines 135 and 136, through interaction with the electrophihc partner. Mamane recently expanded this concept by replacing the acylating agent with different electrophiles. These combinations lead exclusively to isomers 134 (Scheme 18) [118-120]. 

Nucleophilic addition of 1005 to an 7V-acyliminium ion, e.g., a Reissert salt, and oxidation of the resulting adduct affords a 2-(heteroaryl)oxazole 1019. Acylation of a nitrogen heterocycle 1016 with ethyl chloroformate generated the intermediate Reissert salts 1017 in situ (Scheme 1.272). Addition of 1005 to 1017 gave adducts 1018, which produced 1019 after oxidative deacylation with o-chloranil. Examples of 2-(heteroaryl)oxazoles prepared from thiazole, benzothia-zole, pyridine, quinoline, and isoquinoUne are shown in Table 1.77. Donodni and co-workers summarized their early work on preparation and reaction of 2-(trimethylstannyl)oxazoles and 2-(trimethylsilyl)oxazoles. 

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>. 

Elaboration of isoquinoline derivatives in asymmetric fashion was examined as well in 2001. In a manner similar to that described in section 6.1.3.2, an enantioselective Reissert-type reaction was utilized to construct a chiral, quaternary center at the Cl position of isoquinoline derivatives. For example, treatment of isoquinoline 85 with vinyl chloroformate and TMSCN in the presence of bifunctional catalyst 86 afforded isoquinoline derivatives such as 87 in up to 95% ee. The effect of the R group at the 1-position and the catalyst counterion were detailed. 

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