2- Pyrrolines Subject

Volume 75 concludes with six procedures for the preparation of valuable building blocks. The first, 6,7-DIHYDROCYCLOPENTA-l,3-DIOXIN-5(4H)-ONE, serves as an effective /3-keto vinyl cation equivalent when subjected to reductive and alkylative 1,3-carbonyl transpositions. 3-CYCLOPENTENE-l-CARBOXYLIC ACID, the second procedure in this series, is prepared via the reaction of dimethyl malonate and cis-l,4-dichloro-2-butene, followed by hydrolysis and decarboxylation. The use of tetrahaloarenes as diaryne equivalents for the potential construction of molecular belts, collars, and strips is demonstrated with the preparation of anti- and syn-l,4,5,8-TETRAHYDROANTHRACENE 1,4 5,8-DIEPOXIDES. Also of potential interest to the organic materials community is 8,8-DICYANOHEPTAFULVENE, prepared by the condensation of cycloheptatrienylium tetrafluoroborate with bromomalononitrile. The preparation of 2-PHENYL-l-PYRROLINE, an important heterocycle for the synthesis of a variety of alkaloids and pyrroloisoquinoline antidepressants, illustrates the utility of the inexpensive N-vinylpyrrolidin-2-one as an effective 3-aminopropyl carbanion equivalent. The final preparation in Volume 75, cis-4a(S), 8a(R)-PERHYDRO-6(2H)-ISOQUINOLINONES, il lustrates the conversion of quinine via oxidative degradation to meroquinene esters that are subsequently cyclized to N-acylated cis-perhydroisoquinolones and as such represent attractive building blocks now readily available in the pool of chiral substrates. 

Thermal rearrangement of 0-acyl Af-hydroxycarbamates carrying a cyclopropane substituent was reported (equation 255). When subject to flash vacuum thermolysis at 500 °C the carbamate 573 generates the Af-acyl imine 574 that rearranges to pyrroline 577 in 21-37% yield. The formation of a biradical intermediate 575 or a polar zwitterionic structure 576 was proposed. 

Another possible route to thienamycin (487) has utilized the dipolar cycloaddition of 1-pyrroline 1-oxide (482) with methyl crotonate (79TL4359). The reaction is highly stereoselective due to the operation of secondary orbital effects. The isoxazolidine (483), produced in 90% yield, was subjected to hydrogenolysis, and the resulting amino alcohol (484) was selectively blocked with hexamethyldisilazane to give (485). Treatment with ethylmagnesium bromide then gave /3-lactam (486 Scheme 107). 

The opening of activated cyclopropanes with nitrogen nucleophiles has been widely applied to the synthesis of pynolizidine and pyrroline alkaloids by Danishefsky this subject has been reviewed. A number of pyrroline annulations have been based on this principle, illustrated in equation (35a). > Similar opening can be accomplished with halides, cuprates, and sulfur or selenium nucleophiles. ... 

Photochemical rearrangements have also been reported, as shown in equation (53). " Transition metal catalyzed rearrangement [palladium(O)] of a dienylaziridine has been reported in one case, and a radical opening of a dienylaziridine led to pyrroline formation under the conditions of radical initiation with AIBN/PhsSnH (equation 54). For those vinylaziridines that contain additional unsaturation, the corresponding aza equivalent of a divinylcyclopropane Cope rearrangement is the usual pathwayThe subject of heterodivinylcyclopropane Cope rearrangement is covered in detail elsewhere." The... 

Examples of photorearrangement in nitrones and heteroaromatic N-oxides have again been described, and the subject has been critically reviewed. The hydroxyoxaziridines (81) have been prepared by irradiation of the corresponding 1-pyrroline 1-oxides (82), ° whereas photorearrangement of the dinitrone (83) gave the oxaziridines (84) and (85) and the lactam (86) oxaziridines (84), (85), and (86) were converted into the piperazine-2,5-dione (87) by further irradiation. ... 

The earliest work on this subject dealt with the basic behaviour of pyrrolines and tetrahydropyridines, and resulted in the development of a model according to which tertiary enamines would be more basic than their corresponding saturated amines. Later, Stamhuis and coworkers questioned this hypothesis by claiming that Af-isobute-nylpyrrolidine, AT-isobutenylpiperidine and iV-isobutenylmorpholine were less basic than their corresponding saturated amines, Table 2 gathers the most significant data on tertiary amines in this respect. 

Somfai s group demonstrated the use of a Lil-promoted vinylaziridine-3-pyrroline rearrangement in the formal synthesis of the antibiotic (-)-anisontycia The commercially available 2-(4-methoxyphenyl)acetaldehyde 43 was subjected to Brown allylation followed by aminolysis of the resulting chlorohydrin to afford the enantioenriched aminoalcohol 44 f Scheme 11.34). The enantiopure cis-vinylaziridine 45 was then prepared by O- and N-tosylation of the chiral aminoalcohol followed by KOH-promoted ring closure. Microwave-assisted rearrangement of vinylaziridine 45 using Lil as an additive afforded enantioenriched 3-pyrroline 46 in excellent yield, and this was converted to the natural product in several steps tScheme 11.34T ... 

Fig. 6. The effect of P5C on pentose phosphate pathway (HMP) activity and phosphoribosyl pyrophosphate (PPRP) in human erythrocytes. Measurements were performed on incubated erythrocytes from 6 normal subjects. The concentration of pyrroline-5-carbox-ylate (PC) was 0.5 mM. Taken from ref. (116).

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