A Novel Synthesis of 2-Azabicyclo[2.1.1]hexane from Pyridine

Krow, Grant R.; Lee, Yoon B.; Lester, Walden S.; Christian, Hermona; Shaw, Donald A.; Yuan, Jing

doi:10.1021/jo9808472

Cited by 40 publications

(39 citation statements)

References 10 publications

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“…For the 5- anti -hydroxy series, N -BOC-5- anti -alcohol 13a was prepared from bromoacetate 32 , 17 as shown in Scheme 6. Reductive debromination gave acetate 33 .…”

Section: Resultsmentioning

confidence: 99%

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Synthesis of Conformationally Constrained 5-Fluoro- and 5-Hydroxymethanopyrrolidines. Ring-Puckered Mimics of Gauche- and Anti-3-Fluoro- and 3-Hydroxypyrrolidines

et al. 2011

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N-Acetylmethanopyrrolidine and its four 5-syn/anti-fluoro and hydroxy derivatives have been synthesized from 2-azabicyclo[2.2.0]hex-5-ene, a 1,2-dihydropyridine photoproduct. These conformationally constrained mimics of idealized Cβ-gauche and Cβ-anti conformers of pyrrolidines were prepared in order to determine the inherent bridge bias and subsequent heteroatom substituent effects upon trans/cis amide preferences. The bridgehead position and also the presence of gauche(syn)/anti-5-fluoro or 5-hydroxy substituents have minimal influence upon KT/C values of N-acetylamide conformers in both CDCl3 (43–54% trans) and D2O (53–58% trans). O-Benzoylation enhances the trans amide preferences in CDCl3 (65% for a syn-OBz, 61% for a trans-OBz) but has minimal effect in D2O. The synthetic methods developed for N-BOC-methanopyrrolidines should prove useful in the synthesis of more complex derivatives containing α-ester substituents. The KT/C results obtained in this study establish baseline amide preferences that will enable determination of contributions of α-ester substituents to trans-amide preferences in methanoprolines.

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“…For the 5- anti -hydroxy series, N -BOC-5- anti -alcohol 13a was prepared from bromoacetate 32 , 17 as shown in Scheme 6. Reductive debromination gave acetate 33 .…”

Section: Resultsmentioning

confidence: 99%

“…According to the general procedure, AIBN (600 mg) and (TMS) 3 SiH (10.45 mL, 33.8 mmol) were added to bromoacetate 17 32 (6.00 g, 16.9 mmol) in dry toluene (300 mL). The resulting solution was stirred vigorously at 70 °C for 3 h under an argon-filled balloon.…”

Section: Methodsmentioning

confidence: 99%

Synthesis of Conformationally Constrained 5-Fluoro- and 5-Hydroxymethanopyrrolidines. Ring-Puckered Mimics of Gauche- and Anti-3-Fluoro- and 3-Hydroxypyrrolidines

et al. 2011

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“…We have recently described a simple four-step route from pyridine to the 2-azabicyclo[2.1.1]hexane ring system . It was envisioned that application of the protocol of Beak13a to the N -BOC-2-azabicyclo[2.1.1]hexane 4 could be used to generate a lithio anion 5 and that subsequent addition of electrophiles (CO 2 , ClCOOMe, DMF) could be used to generate structures 6a − d , desirable derivatives of 3,5-methanoproline 2 .…”

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Complex-Induced Proximity Effects. Temperature-Dependent Regiochemical Diversity in Lithiation−Electrophilic Substitution Reactions of N-BOC-2-Azabicyclo[2.1.1]hexane. 2,4- and 3,5-Methanoprolines

et al. 2002

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[reaction: see text] Azabicycle 4 and sec-butyllithium/TMEDA afford the C(1) bridgehead alpha-lithio anion at 0 degrees C. Anion quenching with carbon dioxide, methyl chloroformate, or DMF provide the bridgehead acid 8a (N-BOC-2,4-methanoproline), ester 8b, or aldehyde 8c, respectively. By contrast, at -78 degrees C these same reagents give a mixture of regioisomeric methylene and bridgehead anions whose quenching leads to mixtures of regioisomeric methylene and bridgehead acids 6a/8a, esters 6b/8b, or aldehydes 6c/8c, respectively. The previously unknown 3,5-methanoproline was prepared as its N-BOC methyl ester 6b.

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“…5 The synthesis of 5-hydroxy-2-azabicyclo[2.1.1]hexanes has been described by Krow et al using a rearrangement of an appropriate bromohydrin. 6 Huet and co-workers recently reported an interesting synthesis of 5-substituted 2-azabicyclo-[2.1.1]hexanes using an intramolecular nucleophilic substitution of a cyclobutane derivative as the key step. 7 Our approach to construct the 2-azabicyclic skeleton consists of an intramolecular ring closure of an amino acid which contains a four membered ring.…”

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confidence: 99%