Synthesis and photooxygenation of homochiral 2-methylpyrrole derivatives of chiral amino alcohols: simple, selective access to chiral bicyclic lactams

Aydoğan, Feray; Demir, Ayhan S.

doi:10.1016/j.tetasy.2003.11.011

Cited by 21 publications

(13 citation statements)

References 38 publications

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“…In 2004, Demir subsequently illustrated that the oxidation of pyrroles 47 that feature pendant chiral N ‐substituents containing terminal alcohols led to the formation of bicyclic 2‐pyrrolin‐3‐ones 48 through intramolecular cyclization at the 2‐position of the ring (Scheme ) . Moderate yields of mixed stereoisomeric 2‐pyrrolin‐3‐ones 48 were obtained by this process, with some bias toward one diastereomer in each case.…”

Section: Oxidation Of Pyrrole With Singlet Oxygenmentioning

confidence: 99%

The Oxidation of Pyrrole

Howard

Rihak

Bissember

et al. 2015

Chemistry An Asian Journal

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The dearomatization of heterocycles has been a powerful means for producing functional molecules in synthesis. In the case of pyrroles, reductive methods (such as the Birch reduction) have been most widely exploited, while oxidative methods are generally dismissed as too difficult or unpredictable to be useful. However, since the early twentieth century considerable research has been carried out on the controlled oxidation of pyrroles to give highly functionalized products, using a variety of oxidants. This review presents a summary of all work up until the present day in the area of pyrrole oxidation, looking at the use of peroxide, singlet oxygen, hypervalent iodine reagents, a range or organic and inorganic oxidants, and electrochemical approaches. It also offers some perspective on the potential future role of pyrrole oxidation in synthesis.

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Section: Oxidation Of Pyrrole With Singlet Oxygenmentioning

confidence: 99%

The Oxidation of Pyrrole

Howard

Rihak

Bissember

et al. 2015

Chemistry An Asian Journal

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“…In this study, we have explored the origin of selectivity in the diastereoselective synthesis of trans -pyrrolooxazolones via photooxidation of a homochiral N-substituted 2-methylpyrrole with 1 O 2 (Scheme ) . For this purpose, we have initially investigated the relative stabilities of ( S )- 1 's conformers, to rationalize the π-facial selectivity in the cycloaddition of singlet oxygen to the pyrrole ring.…”

Section: Resultsmentioning

confidence: 99%

“…In light of the results and discussions drawn for the singlet oxygen photooxygenation of ( S )- N -(hydroxyalkyl)-2-methylpyrrole, ( S )- 1 , it is worthwhile to take a look at the ( R )- N -(hydroxyalkyl)-2-methylpyrrole. Experiments have shown that the photooxygenation of the ( R )-2-(2-methyl-1 H -pyrrol-1-yl)-3-methylbutan-1-ol, ( R )- 1 , has likewise led to a diastereomeric mixture of ( R , RS )-3-isopropyl-7a-methyl-2,3-dihydropyrolo[2,1 b ][1,3]oxazol-5(7a H )-one, where the trans ( R , R ) and cis ( R , S ) products formed in a 5:1 isomeric ratio …”

Section: Resultsmentioning

confidence: 99%

“…Bicyclic lactams, with quaternary stereocenters, are valuable intermediates for many bioactive compounds . Although, synthetic routes leading to cis-bicyclic lactams have been previously reported,3b the synthesis of trans isomers of these compounds is relatively new …”

Section: Introductionmentioning

confidence: 99%

“…Recent studies on the photooxygenation of homochiral N -(hydroxyalkyl)-2-methylpyrroles with 1 O 2 furnished trans -pyrrolooxazolones in high diastereoselectivity . The photooxygenation of the homochiral ( S )-2-(2-methyl-1 H -pyrrol-1-yl)-3-methylbutan-1-ol, ( S )- 1 , led to a diastereomeric mixture of ( S , RS )-3-isopropyl-7a-methyl-2,3-dihydropyrolo[2,1 b ][1,3]oxazol-5(7a H )-one, where the trans ( S , S ) and cis ( S , R ) products formed in a 5:1 isomeric ratio (Scheme ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Origin of Diastereoselectivity in the Synthesis of Chiral Bicyclic Lactams: π-Facial Selective Attack of Singlet Oxygen Induced by Hindered Internal Rotation

et al. 2007

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Previously reported experimental results indicate that photooxygenation of homochiral N-(hydroxyalkyl)-2-methylpyrroles with singlet oxygen yields trans-rather than cis-bicyclic lactams as the major product. In this study, the origin of selectivity in this reaction has been investigated with computational methods. Relative stabilities of homochiral N-(hydroxyalkyl)-2-methylpyrrole conformers and their effect on pi-facial selectivity of 1O2 were extensively studied. Stepwise and concerted reaction mechanisms, starting from the endoperoxide intermediates, were proposed and modeled in vacuum using the UB3LYP method with the 6-31+G** basis set. Solvent calculations were carried out in CH2Cl2, by means of the integral equation formalism-polarizable continuum model (IEF-PCM) at the UB3LYP/6-31+G** level of theory. Free energies of activation leading to both diastereomers were analyzed in an effort to explain the stereoselectivity and product distribution. Steric interactions among the pyrrole substituents were shown to lead to a rotational barrier higher than 10 kcal/mol. Hence, hindered internal rotation is suggested to cause one pyrrole conformer to be substantially overpopulated. This in turn has a major effect on pi-facial selectivity of 1O2, thereby favoring one endoperoxide over the other and leading to the diastereoselective synthesis of trans-pyrrolooxazolones. The importance of hindered internal rotors, for an accurate calculation of the frequency factors of a chemical reaction, has already been mentioned in the literature many times; however, in this work hindered internal rotors also seem to dictate the diastereoselective outcome of the reaction.

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