ISOQUINOLINE ENAMIDES

Tetrahydro-3-benzazepin-2-ones Lead Tetraacetate Oxidation of Isoquinoline Enamides. 

Lead Tetraacetate Oxidative Ring Expansion of Isoquinoline Enamides... 

TETRAHYDRO-3-BENZAZEPIN-2-ONES lead TETRAACETATE OXIDATION OF ISOQUINOLINE ENAMIDES... 

In a study of the mechanism and stereochemistry of the enamide photo-cyclization, Lenz has demonstrated that ethylidene and benzylidene isoquinoline enamides cyclize stereospecifically from the Z-isomer to yield 13-substituted oxoberberines in which the 13-substituent is quasi-axial and the C-13 and C-14 hydrogens are in a cis relationship. ... 

Lenz, G. R. Lessor, R. A. Tetrahydro-3-benzazepin-2-ones Lead Tetraacetate Oxidation of Isoquinoline Enamides OS, (1991), 70, 139. 

The photocyclization of enamides to quinolines or isoquinolines has become an important reaction in the synthesis of alkaloids 219,358). It has recently been applied in the preparation of the isoquinoline alkaloid polycarpine 359). The principle of the reaction is demonstrated in the preparation of dihydroquinolines 360> (3.39) and of spirocyclohexaneisoquinoline derivatives (3.40) 361K In each case the electrocyclic ring closure product undergoes a subsequent 1,5-hydrogen shift. 

Somewhat more effective catalysts are obtained by replacing BINAP with TolBINAP, which is 2,2 -bis(di-p-tolylphosphino)-l,l -binaphthyl.4 The presently preferred catalysts are complexes of Ru(OCOCF3)2 with (R)- or (S)-TolBINAP, obtained by treatment of Ru(OAc)2TolBINAP with 2 equiv. of trifluoroacetic acid. Such catalysts promote hydrogenation of typical enamides in 98% ee and 98% yield. This reaction can be used to provide asymmetric synthesis of isoquinoline alkaloids as well as of morphinans used as substitutes for morphine. 

Isocyanophosphonates, aldol reactions, 227 Isoquinoline synthesis, enamide reactions, 33 Isomerization allylic amines, 9, 95 olefins, 118, 171 see also specific compounds Isopulegol, 102 Isotactic polymers, 174 chloral, 182 photoirradiation, 347 methacrylates, 181 propylene, 174 Isotacticity, 177... 

Isoquinoline Synthesis. Olefins that contain certain neutral donor functionalities are also effectively hydrogenated. Investigation of the enan-tioselective hydrogenation of enamide substrates has resulted in a general procedure for the asymmetric synthesis of isoquinoline alkaloids. 

Started in the late 1960s, studies on enamide photocyclization and its application to the synthesis of alkaloids have been successfully accumulated and have achieved a number of total syntheses of various types of isoquinoline and indole alkaloids and related heterocyclic compounds (11). 

Several reviews on enamide photocyclization (11-13) and photochemical synthesis of isoquinoline alkaloids (14) have been published. 

By taking advantage of these features, enamide cyclization has shown its great versatility in the synthesis of a wide variety of isoquinoline and indole alkaloids. 

The stereochemistry and photocyclization of the corresponding 1 -ethyli-deneenamide 136 has also been studied (24,109). Acylation of the 1-ethyl-isoquinoline with benzoyl chloride afforded a mixture of two enamides of geometrical isomers, the unstable E (136) and stable Z isomers (137), which were easily assigned from the nuclear Overhauser effect data in their NMR spectra (24). 

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 reaction of Ru-binap complexes applied to tetrahydroisoquinoline compounds that have an exocyclic enamide double bond produces 1-substituted tetrahydroisoqui-nolines nearly quantitatively and with optical yield close to 100%. This procedure served in industrial production of benzomorphans, morphinans, and various isoquinoline alkaloids ... 

Two ruthenium complexes, binap 3.43-Ru(OCOR)2(R = Me,CF3) [892] and binap 3.43-RuX2 (X = Cl, Br, I) [893, 894], are quite useful. The acetate and trifluoroacetate complexes of 3.43 induce selective asymmetric hydrogenations of classes of prochiral olefins that are poorly selective with rhodium complexes. These classes include a,(3- or fcy-unsaturated acids and esters, ally alcohols, j3-acylaminoacrylates and enamide precursors of isoquinoline alkaloids [752, 853, 859, 881, 883, 895]. 

Photocyclization of an enamide (review [2S9S]) containing a methoxy group leads to the formation of a pyridinone ring of an intermediate in the synthesis of (— )-sincitine. Reviews of numerous syntheses of isoquinoline alkaloids [2487] and of the use of Reissert compounds in such syntheses [2488] are available. 

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