Reissert compounds, with aldehydes

The Reissert compound (5.7 mmol), an aryl aldehyde and TEBA-C1 (14 mg, 0.06 mmol) in CH,C1, (3 ml) are sonicated with aqueous NaOH (50%, 2.5 ml) for 5 min. EtOH (8 ml) and CH,C1, (15 ml) are added and sonication is continued for a further 85 min and the mixture is then poured into H,0 (20 ml). The aqueous phase is separated and extracted with CH2C1, (3x10 ml). The combined organic solutions are dried (MgS04), concentrated to 20 ml, and saturated with HCI gas to yield the hydroxymethylheteroarene hydrochloride (80-99% ). 

The formation of a Reissert anion (intermediate of type 16) is usually the introductory step in a great number of synthetic routes leading to isoquinoline as well as indole alkaloids and related compounds. On the one hand, the alkylation of a Reissert anion with alkyl halide followed by alkaline hydrolysis is the most frequently used method for the synthesis of 1-alkyl- or 1-arylalkylisoquinolines (20) (Scheme 4). On the other hand, Reissert anions react with aldehydes to form... 

A new synthesis of dibenzo[a,g]quinolizinium derivatives also makes use of an aldehyde cyclization (Scheme 80) (75JAP(K)7596599). In one example, a benzyl bromide bearing an acetal-masked aldehyde group in the ortho position (126) was allowed to react with the anion (127) generated by the action of phenyllithium on a Reissert compound. The condensation product was heated with alkali to cleave the benzoyl and cyano groups to yield the isoquinoline (128), then the acetal was cleaved and the resulting aldehyde cyclized to (129), presumably under acid conditions. 

FMOC-protected amino acid fluorides afford the expected Reissert adducts 160 with a good stereoselectivities, the a-sulfonylamino acid fluorides undergo cycliza-tion to adduct 161 [47, 140, 141], Itho s protocol is amenable to using silyl enol ethers 157 as nucleophiles [142], Gibson has used bulky asymmetric acid chlorides as substrates in a Reissert reaction with TMS-CN the corresponding Reissert compound was then treated with aldehydes and sodium hydride to obtain the enantiopure adducts 4 (Scheme 3) [143],... 

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]. 

The anions of Reissert compounds 19 and 20 undergo reaction with aldehydes to form esters of secondary alcohols containing the 2-quinolyl or 1-isoquinolyl group bonded to the carbinol carbon atom. Thus benzaldehyde, l-benzoyl-l,2-dihydroquinaldonitrile (7), and phenyllithium in ether-dioxan at — 10° gave 29, and benzaldehyde, 2-benzoyl-l,2-dihydroisoquinaldonitrile (8), and phenyllithium in ether-dioxan at —10° (or sodium hydride in refluxing... 

As in the previous chapter, the material will be organized according to substrate category, starting with the carboxylic acids themselves and then moving on to the various derivatives. The methods have been placed generally in sections corresponding to the immediate precursors of the aldehydes. Thus, the hydrolysis of Reissert compounds appears under amides as opposed to acyl chlorides, and the Sonn-Muller appears under imidoyl chlorides and not amides. 

Reissert Compounds Compounds such as 44 are prepared from the acyl halide by treatment with quinoline and cyanide ion. Treatment of 44 with sulfuric acid gives the corresponding aldehyde. 

Reissert reaction. Formation of l-acyl-2-cya-no-l,2-dihydroquinoline derivatives (Reissert compounds) by reaction of acid chlorides with quinoline and potassium cyanide hydrolysis of these compounds yields aldehydes and quinaldic acid. 

Except for a demonstration that the phthalazine Reissert compound (3 R = Ph) behaves normally in giving benzaldehyde on acid-catalyzed hydrolysis, no new reports have appeared of Reissert compounds being used in aldehyde synthesis. Acid-catalyzed hydrolysis has been used, however, in some cases to prepare heterocyclic carboxylic acids. Thus in addition to the preparation of isoquinaldic acid, phthalazine-1-carboxyIic acid and 15 have been prepared from 3(R = Ph) and 11, respectively. Acid-catalyzed hydrolysis of 16 occurs with cyclization to give 17. A series of Reissert compounds derived from substituted 3-aminoquinolines have been converted to the corresponding quinaldic acids by acid-catalyzed hydrolysis. ... 

In addition to the conventional sodium hydride method of anion generation, organolithium compounds 50% aqueous sodium hydroxide in acetonitrile and 50% sodium hydroxide with a phase transfer catalyst have been used to generate the anion of Reissert compounds for condensation with aldehydes. A variety of substituted benzaldehydes have been allowed to react with anions of type 26 to give45. ° - ... 

Several of the condensations with aromatic aldehydes have been used in the synthesis of alkaloid systems. 2-Nitrobenzaldehydes have been used in synthetic routes to 7-hydroxyaporphines/°° and 2-iodobenzaldehydes have been used in oxidative photochemical routes to the aporphines and oxoapor-phines caaverine, isoboldine, corunnine, and nandazurine. ° The aldehyde 46 has been used with the anion of the Reissert compound derived from... 

Polymeric aldehydes such as47 ° and poly(vinylbenzaldehyde-co-vinylbenzaldehyde hydrate) react with 26 to give polymers such as 48. The anion of the quinoline Reissert compound (1) reacts with 47 to give a similar polymer. ... 

A variety of other, nonaromatic, aldehydes with 26 have also given the expected esters.Ferrocenecarboxaldehyde has been allowed to react with the anions of both the quinoline and isoquinoline Reissert compound. Benzaldehyde and other aromatic aldehydes have been condensed with the anion of the phthalazine Reissert compound. 

Another procedure for converting carbonyl chlorides into aldehydes proceeds by way of Reissert compounds.3448 Reissert found that 1-benzoyl-1,2-dihydro-2-quinolinecarbonitrile is formed in very good yield when benzoyl chloride reacts with quinoline in the presence of aqueous potassium cyanide, the technique being that of a Schotten-Baumann reaction the nitrile can then be hydrolysed to benzaldehyde and quinaldic acid by acid. 

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. 

Stabilized carbanions can be easily generated at activated positions. An example is that of the Reissert compound shown in Eq. 13, which imdergoes deprotonation in a dichloromethane-water system in the presence of TEBAC, then condenses with aldehydes.54 The alkylation of the anion is discussed below (p. 138). 

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. ... 

Reissert s compound (l-cyano-l,2-dihydroquinolinyl benzamide) is apparently de-protonated under phase transfer conditions at the one-carbon as expected. The condensation of the carbanion with an aldehyde or ketone leads to an N-benzoyl alk-oxide in which oxygen acylation (N ->0 acyl transfer) results in five-membered ring formation. The intermediate oxazolidine decomposes with loss of cyanide to give the benzoate ester of an isoquinolinoylcarbinol as shown in equation 10.26 [36]. 

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