Succinimide, reduction

Most ring syntheses of this type are of modern origin. The cobalt or rhodium carbonyl catalyzed hydrocarboxylation of unsaturated alcohols, amines or amides provides access to tetrahydrofuranones, pyrrolidones or succinimides, although appreciable amounts of the corresponding six-membered heterocycle may also be formed (Scheme 55a) (73JOM(47)28l). Hydrocarboxylation of 4-pentyn-2-ol with nickel carbonyl yields 3-methylenetetrahy-drofuranone (Scheme 55b). Carbonylation of Schiff bases yields 2-arylphthalimidines (Scheme 55c). The hydroformylation of o-nitrostyrene, subsequent reduction of the nitro group and cyclization leads to the formation of skatole (Scheme 55d) (81CC82). 

More symmetrical imides may still be regioselectively reduced. In the case of geminally disub-stituted succinimidcs the stcrically more hindered carbonyl function is preferentially reduced with sodium borohydride. The regioselectivity ranges from 79 21 for the dimethyl derivative to > 95 5 for the diphenyl derivative29. For monosubstituted succinimides the selectivity of the reduction is low29, unless the substituent is an acetoxy group35-36. 

Miscellaneous Compounds. A saturated spirocychc pyrrohdine serves as the nucleus for a diamine that has been described as a hypohpemic agent. Treatment of the carbanion of the substituted cylcohexane carboxyhc ester (20-1) with methyl bromoacetate leads to the alkylation and formation of the diester (20-2). Saponification of the ester groups followed by reaction with acetic anhydride leads to ring closure of the succinic anhydride (20-3). Condensation with ammonia leads to the succinimide (20-4). The side chain is then added by alkylation of the anion on nitrogen with l-bromo-4-dimethylaminobutane (20-5). Reaction of this last intermediate with lithium aluminum hydride leads to the reduction of the carbonyl groups to methylene. This affords the pyrrolidine (20-6) atiprimod [22]. 

Regioselective reduction of a succinimide intermediate for a (-i-)-heliotridine synthesis [269] must be due to the influence of the acetoxy group. It is conjectured that the a-a array of the intervening carbon atoms activates the carbonyl. Steric effects should he minimal on the choice of the two sites. 

Catalytic hydrogenation of porphyrazines or their Mg complexes with palladium black gives tetrahydrogenated compounds which are oxidized back to the starting materials by a stoichiometric amount of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ).2 The royal blue products are degraded to cw-succinimide and maleimide, and considered to be the tetraaza analogues of either bacterio-chlorins or isobacteriochlorins. Photochemical reduction of monoazaporphyrins is reported to occur at the meso positions. 

Thiiranes can be formed directly and stereospecifically from 1,2-disubstituted alkenes by addition of trimethylsilylsulfenyl bromide, formed at -78 C from reaction of bromine with bis(trimethylsilyl) sulfide (Scheme 7).12 A two-step synthesis of thiiranes can be achieved by addition of succinimide-A/-sulfe-nyl chloride or phthalimide-A -sulfenyl chloride to alkenes followed by lithium aluminum hydride cleavage of the adducts (Scheme 8).13 Thiaheterocycles can also be formed by intramolecular electrophilic addition of sulfenyl chlorides to alkenes, e.g. as seen in Schemes 914 and 10.13 Related examples involving sulfur dichloride are shown in Schemes 1116 and 12.17 In the former case addition of sulfur dichloride to 1,5-cyclooctadiene affords a bicyclic dichloro sulfide via regio- and stereo-specific intramolecular addition of an intermediate sulfenyl chloride. Removal of chlorine by lithium aluminum hydride reduction affords 9-thiabicyclo[3.3.1]nonane, which can be further transformed into bicyclo[3.3.0]oct-1,5-ene.16... 

Some reductases isolated from tobacco (Nicotiana tabacum) were found to exhibit excellent enantioselectivities on the reduction of a number of a,/i-unsaturated compounds [140,141]. For example, reductase p44 catalyzed the asymmetric reduction of A-phenyl-2-methylmaleimide. yielding the enantiopure (7 )-succinimide. Reductase p90 mediated the enantioselective hydrogenation of a number of methyl or ethyl substituted cyclopentenones and cyclohexanones (Fig. 20). 

There were relatively few examples reported, in which the chromo-phoric group was an aryl ketone (Ilia) whereas much more PET induced cyclizations with phthalimides (Illb) are known, sometimes other imides, such as succinimides and maleimides were also used. Phthalimides differ from aryl ketones in some respects despite their apparently similar photophysical properties. On one hand, their reduction potential is remarkably lower in comparison with aryl ketones [13]. On the other hand, the radical anion derived from phthalimides is clearly more stable than the corresponding species from aryl ketones [15]. Both facts increase the thermodynamic driving force of a PET and facilitates applications that are unknown from aryl ketones. In this context, one of the most successful approaches is a PET-induced decarboxylation-cyclization route, developed by Griesbeck [13]. The details of this interesting method will be discussed in Sec. 3.4.6. 

The synthesis of the derivatives (339)-(346) was carried out as shown in Scheme 28. Metalation of the acetal (336), followed by thiolation and alkylation, gave the ester derivative (337). Acetal deprotection to form (338) and subsequent treatment under Knoevenagel conditions with piper-idinium acetate in benzene afforded the desired ester (339). Reduction of compound (339) gave alcohol (340), which was converted to aldehyde (341) and protected as its acetal (342) under standard conditions. Deprotonation was effected by Bu"Li in THF at — 78 °C and subsequent conversion to the sulfonyl chloride was carried out by sequential treatment with sulfur dioxide and A-chloro-succinimide. Treatment of the sulfonyl chloride (343) with concentrated NH4OH in acetone provided the sulfonamide (344), which was deprotected (345) and subjected to reductive amination to provide compounds in the aminomethyl sulfonamide series (346). 

More synthetic routes to the l-(hydroxymethyl)pyrrolizidines have been reported. Two groups3,4 have published the same route to ( )-isoretronecanol (3) (Scheme 1). The key step is the nucleophilic attack of succinimide anion on the cyclopropylphosphonium salt (1), followed by intramolecular Wittig reaction to generate the unsaturated pyrrolizidinone ester (2). Catalytic reduction and reduction with a hydride yielded ( )-isoretronecanol (3). Flitsch and Wernsmann achieved a higher overall yield (62%) by carrying out the first step in boiling xylene.3... 

In a study focusing on the synthesis and reactions of 2-(2-aminoethyl)pyrroles, a preparation of the tricyclic ring-system 64 was accomplished by reduction of the succinimides 65, followed by cyclization of the intermediates 66. Moreover, 2-(2-aminoethyl)pyrroles were demonstrated to undergo cyclization with aldehydes to provide 4,5,6,7-tetrahydropyrrolo[3,2-c]pyridines <03T5265>. 

The above directions are based upon the methods of Hoogewerff and Van Doip, as modified by Holm and by Hale and Honan. -Alanine has also been prepared by the action of h3q)obromite upon succinimide and hydrolysis of the resulting /3-ureidopropionic acid by the action of ammonia upon /3-iodo-propionic acid by the hydrolysis of methyl carbomethoxy-/8-aminopropionate, obtained by the action of sodiiun methoxide on succinbromimide by the reduction of 3-nitrosopropionic acid by heating ethyl acrylate with alcoholic ammonia from succinyl-glycine ester by the azide synthesis and by the action of liquid ammonia upon methyl acrylate. ... 

Controlled potential electrolysis at a mercury pool cathode, carried out at the plateau of the first reduction wave of At-(2-nitrobenzoyl)acetamide, leads in practically quantitative yield to 2-methylquinazolin-4(3/f)-one 1-oxide (mp >260°C), resulting from a ring closure of the A-phenylhydroxylamine intermediate. 2-Methylquinazolin-4(3//)-one 1-oxide is further reduced in Sulfuric acid media to give 2-methylquinazolin-4(3//)-one. A -(2-Nitrobenzoyl)-succinimide and A-(2-nitrobenzoyl)phthalimide undergo similar electrochemical reduction and cyclization to quinazoline derivatives. ... 

Pyrrolidine is also obtained from succinimide by reduction H2C—CH2 HoC—CH2... 

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