Tetrahydroisoquinolin-l-ones

The mechanism of palladium-catalyzed intramolecular cyclization of o-bromo(aminoalkyl)benzenes has been discussed earlier (see Scheme 50 in Section IV,A,4). This approach is illustrated by the preparation of 1,2,3,4-tetrahydroisoquinolin-l-ones in Scheme 146,86 and examples of applications in benzazepinone synthesis are given later (see Scheme 173 in Section VI,B). 

Recyclization of hydrazides 38 was carried out by treatment with pTsOH H20 gave 3,4-dihydro-l OH-pyridazino [1,6-b] isoquinolin-10-ones 37 via tetrahydroisoquinolin-l-ones 39 (06SL3431, 07S2208). 

V-Substituted-1,2,3,4-tetrahydroisoquinolin-l-ones (26) can be prepared in good yield by carbonyla-tion of A/-alkyl-o-bromophenefliylamines in the presence of catalytic amounts of Pd(OAc)2/PPh3. Similarly substituted 2-(2-bromoanilino)pyridines undergo carbonyl insertion to produce pyrido[2,l-b]quinazoline derivatives in good yield (equation S7). ... 

Substituted a-tetralones. 3-Aroylpropyl xanthates undergo desulfurative cycliza-tion on treatment with dilauroyl peroxide in 1,2-dichloroethane. Similarly, 1,2,3,4-tetrahydroisoquinolin-l-ones are prepared.- ... 

Tetrahydroisoquinolin-l-ones. A significantly improved reagent for cyclization of phenylethylcarbamates is the PjOj-POClj combination. ... 

Lateral Lithiation. An enantioselective synthesis of tetrahydroisoquinolin-l-ones via a BuLi/(—)-sparteine-mediated lateral metalation-imine addition sequence proceeds with highest yields and induction in toluene/ether mixtures (eq 46). ... 

Treatment of (11 aS)-3-isopropyl-11 a-methyl-4-phenyl-1,6,11,11 a-tetrahy-dro[l,4]oxazino[4,3-6]isoquinolin-l-one (243) with 6N HCl in a pressure tube, then the reaction of the work-up residue with propylene oxide gave (3S)-3-methyl-l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (244) (99S704). 

Additions of stabilized carbanions to imines and hydrazones, respectively, have been used to initiate domino 1,2-addition/cyclization reactions. Thus, as described by Benetti and coworkers, 2-subshtuted 3-nitropyrrolidines are accessible via a nitro-Mannich (aza-Henry)/SN-type process [165]. Enders research group established a 1,2-addition/lactamization sequence using their well-known SAMP/ RAMP-hydrazones 2-308 and lithiated o-toluamides 2-307 as substrates to afford the lactams 2-309 in excellent diastereoselectivity (Scheme 2.72) [166]. These compounds can be further transformed into valuable, almost enantiopure, dihydro-2H-isoquinolin-l-ones, as well as dihydro- and tetrahydroisoquinolines. 

Treatment of pyrimidine-2-thione 184 with A1C13 yielded 6-oxo-6,7-dihydro-4//-pyrimido[6,l-tf]isoquinolin-4-thione 185 (Equation 37) <1998MI337>. Cyclization of 6,7-diethoxy-2-propylaminocarbonyl-l,2,3,4-tetrahydroisoquinoline-l-acetonitrile using NaOMe afforded 9,10-diethoxy-2-imino-3-propyl-l,2,4,6,7,l lb-hexahydropyrimido[6,l-tf]isoquinolin-4-one <1995S863>. Cyclization of l-(2-carboxyethyl)-l,2,3,4-tetrahydroquinazoline-2,4-dione 186 in polyphosphoric acid (PPA) afforded l,2,3,5,6,7-hexahydropyrimido[3,2,T /]quinazoline-l,3,7-trione 187 (Equation 38) <1997CHE96>. 

Reaction of tetrahydroisoquinoline-3-carboxylic acid 434 with primary amines and isonitriles provided 1,2,3,4, 1,11 -hexahydro-6H-pyrazino [l,2-b]isoquinolin-l-ones 435 (06HEC107). 

Tetrahydroisoquinolin-4-ones. 3-Alkoxy-l,2,3,4-tetrahydroisoquinolin-4-ol derivatives undergo rearrangement to give the ketones. 

Perhydropyrido[l,2-c][l,3]oxazin-l-ones were prepared in the reaction of the appropriate 2-(2-piperidyl)ethanols and ethyl chloroformate (63AP38) in the presence of sodium ethylate in boiling benzene, or when 2-(2-piperidyl)ethanol was reacted with dimethyl carbonate in the presence of sodium methylate (91X1311). l-Hydroxymethyl-9,10-dimethoxy-l,2,4,6,7,llb-hexahydro-[l,3]oxazino[4,3-fl]isoquinoline-4-oneand 4-thione were prepared from l-[bis(hydroxymethyl)methyl]-6,7-dimethoxy-l,2,3,4-tetrahydroisoquinoline with ethyl chloroformate in the presence of sodium methylate, and thiophosgene in the presence of NEts, respectively... 

A variety of spiro-tetrahydroisoquinoline-piperidines have been synthesized by established routes. The compounds and methods include (30) by a Pictet-Spengler-type reaction, (31) by cyclization of an N-3,4-dimethoxybenzylglycine nitrile derivative, and (32) via Schmidt rearrangement of a 3-spiro-indan-l-one derivative. ... 

Intramolecular photoelimination of HCl from A -chloroacetamide derivatives is also a useful and versatile approach to the synthesis of aza-heterocycles. The N-alkyl-jV-chloroacetyl derivatives (202), for example, undergo photocyclization to the l,2,3,4-tetrahydroisoquinolin-3-ones (203), and the conversion of the N-chloroacetamide (204) into the lactam (205) is the key step in a synthesis of 20-de-ethylcatharanthine. Intermolecular photoeliminations of HX of potential... 

Carbomethoxy-6,7-dimethoxy-1 -methylene-1,2,3,4-tetrahydroisoquinoline treated with Pb(OAc)4 in acetic acid, and quenched with glycerine almost immediately product. Y 76%. F.e. incl. N-acyl-derivs. s. G.R. Lenz, J. Org. Chem. 53, 5791-3 (1988) N-acyl-3,4,5,6-tetrahydro-3-benzazocin-2(l//)-ones s. J. Chem. Soc. Perkin Trans. I 1989, 1931-8. 

The rhodium(II) acetate catalyzed reaction of 2-(3-oxo-2-diazobutyryl)-1,2,3,4-tetrahydroisoquinoline in boiling toluene yielded 2-methyl-4,6,7,l 16-tetra-hydro[l, 3]oxazino[2,3-n]-isoquinoline-4-one in 72% yield (99TL8269). 

Reactions of 3-methyl-1,2,3,4-tetrahydroisoquinoline-1-acetamides 202 (R = H) with 36% aqueous CH2O at 60 °C gave 1,3,4,6,7,1 Ih-hexahydro-2//-pyrimido[6,l-a]isoquinolin-2-ones 152 and their 3-methyl derivatives (97LA1165). When the reaction was carried out in the presence of 37% aqueous NaOH 3-hydroxymethyl derivatives 151 were obtained. Reactions with PhCHO were stereospecific to afford only diastereomers 203. 

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