Pyrrolizines synthesis

The 1,2-dihydropyridines are also known to undergo [2 + 2] cycloadditions of the enamine double bond with alkynes (74JCS(P1)2496). The products of these reactions are azocine derivatives such as (259), which, after removal of the A-protecting group, have been used as intermediates in pyrrolizine synthesis (Scheme 47) (77JOC2903). 

Also in 2001, Azizian described a one-pot diastereoselective synthesis of 2-sub-stituted l,l,2,3,3aa,3b) ,4,5,6,8,8aa-decahydro-8-(spiro-3-indolino-2-one)pyrrolo[3,4-b] pyrrolizine-l,3-dione (151) in good yield and diastereomeric excess using microwave irradiation (Scheme 9.46). 

Dipolar cycloadditions of 2-tert-butoxycarbonyl-1 -pyrroline A -oxide (627) with several chiral acrylamides (634a-f) (Scheme 2.276) followed by hydrogenolysis of cycloadducts (635) and (636) has been used in the synthesis of enantiopure tert-butyl (2RJ R)- and (2.S. 7a.S )-2-hydroxy-3-oxo-tetrahydro-l II -pyrrolizine-7a(5// )-carboxylates, useful intermediates for the synthesis of Gly-(s-cis)Pro dipeptide mimetic (790). 

Cyclazines (229) are stable aromatic compounds, the synthesis of which may involve indolizines, 3H-pyrrolizines or pyridines. Their chemistry has been investigated extensively. 

There are numerous studies on the synthesis of pyrrolizines from enam-ines. In these reactions, one of the step is the closure to a new hydrogenated pyrrole ring. In polar solvents, the reaction of enamines with dimethyl acetylenedicarboxylate follows two different pathways, the formation of cycloadducts (18) and Michael adducts (19) (81T3525). Subsequent studies of this reaction have demonstrated (by low-temperature NMR) that compounds of the type 20 are intermediates in this cyclization (83JA4775). On the basis of this information (83JA4775), the authors then studied this type of cyclization using dienamines (21). The reaction follows the scheme shown, with a [1,6] antarafacial hydrogen shift and the formation of a dipo-... 

Pyrrolizines have been studied for theoretical reasons. They are intermediates in synthesis and are important natural products. Synthetic studies of the cytostatic mitomycins have aroused further interest.1-6... 

A new metabolite from Streptomyces olivaceus has been shown to be (2S)-1-oxo-2,3-dihydropyrrolizine-3-carboxylic acid (15b) by total synthesis. The pyrrolizine ring was formed from the pyrrole (14) by stereoselective cyclization with phosphorus pentoxide in toluene in 37% yield. Partial racemization occurred during the hydrolysis of ester 15a.21... 

Acids 93a-d were cyclized to 3f/-pyrrolizin-3-ones in yields similar to those obtained for 92. Thus the parent (94a) could be obtained either from 93a or 93b 33 the synthesis of 94c was similar.64... 

A direct synthesis of 3H-pyrrolizin-3-one derivatives has been effected. Reaction of 2-benzoylpyrrole with ylides 148 gave the 3H-pyrrolizin-3-one 149 9 ,92 analogous reaction of 2-formyl pyrroles could be achieved with... 

Functionalization of pyrrolizines and partially hydrogenated pyrrolizines has made possible the synthesis of interesting pyrrolizines (see Section III). Only a few examples are presented in this section because most are described in Section III. 

Much more common but equally confusing is the 3Hz 5H tautomerism, exemplified by equilibrium 211 212. A number of incorrect assignments occur in the early literature when NMR spectra were not available. In many cases equilibrating conditions were used in the synthesis. Of the 1(7)-substituted pyrrolizines, the methyl derivative certainly has the structure... 

W. Flitsch and G. Jones provide the first comprehensive review of pyrrolizine chemistry, an area of increasing interest. The chemistry of the arene oxides has been brought up-to-date by G. S. Shirwaiker and M. V. Bhatt. Following the overall treatment of the electrochemistry of heterocycles given by Lund in Volume 36 of this series, J. E. Toomey has now reviewed electrochemical synthesis and modification of pyridines, a subject of great industrial and academic interest. 

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