New route to azaspirocycles via the organolithium-mediated conversion of beta-alkoxy aziridines into cyclopentenyl amines.

A new three-step route to azaspirocycles involving the organolithium-mediated conversion of beta-alkoxy aziridines into substituted cyclopentenyl amines, hydroboration, and cyclization has been developed. The methodology is utilized in the construction of the pentacyclic ring system of cephalotaxine. [reaction: see text]

[1]  D. Gin,et al.  Strain-release rearrangement of N-vinyl-2-arylaziridines. Total synthesis of the anti-leukemia alkaloid (-)-deoxyharringtonine. , 2006, Journal of the American Chemical Society.

[2]  S. Weinreb.  Studies on total synthesis of the cylindricine/fasicularin/lepadiformine family of tricyclic marine alkaloids. , 2006, Chemical reviews.

[3]  G. Dake.  Recent Approaches to the Construction of 1-Azaspiro[4.5]decanes and Related 1-Azaspirocycles , 2006 .

[4]  J. Ward,et al.  Intramolecular cyclopropanation of unsaturated terminal aziridines. , 2006, Organic letters.

[5]  W. Bailey,et al.  Effect of solvent on the lithium-bromine exchange of aryl bromides: reactions of n-butyllithium and tert-butyllithium with 1-bromo-4-tert-butylbenzene at 0 degrees C. , 2006, The Journal of organic chemistry.

[6]  B. Kariuki,et al.  Synthesis of 3,4-disubstituted piperidines by carbonyl ene and prins cyclizations: switching between kinetic and thermodynamic control with Brønsted and Lewis acid catalysts. , 2006, The Journal of organic chemistry.

[7]  P. O’Brien,et al.  Organolithium-mediated conversion of beta-functionalised aziridines into alkynyl amino alcohols and diamines. , 2005, Chemical communications.

[8]  D. Clive,et al.  Synthetic chemistry of halichlorine and the pinnaic acids. , 2005, Chemical reviews.

[9]  P. O’Brien,et al.  Reductive alkylation of beta-alkoxy aziridines: new route to substituted allylic amines. , 2004, Organic letters.

[10]  J. Paris,et al.  Intramolecular cyclopropanation of unsaturated terminal epoxides. , 2004, Journal of the American Chemical Society.

[11]  D. M. Hodgson,et al.  Studies on organolithium-induced alkylative desymmetrisation of epoxides: synthesis of enantioenriched β-amino cycloheptenols from 6,7-epoxy-8-azabicyclo[3.2.1]octanes ☆ , 2004 .

[12]  P. O’Brien,et al.  On the α-lithiation-rearrangement of N-toluensulfonyl aziridines: mechanistic and synthetic aspects , 2003 .

[13]  E. Doris,et al.  Metalated epoxides as carbenoids. Competing C–H and CC insertion in α-alkoxy epoxide systems , 2003 .

[14]  P. O’Brien,et al.  α-Lithiation-rearrangement of N-toluenesulfonyl aziridines with sec-butyllithium and (−)-sparteine: opposite sense of asymmetric induction to epoxides , 2003 .

[15]  Skrydstrup,et al.  Studies on the SmI2-promoted pinacol-type cyclization: synthesis of the hexahydroazepine ring of balanol , 2000, The Journal of organic chemistry.

[16]  L. Tietze,et al.  Efficient Synthesis of Six‐Membered Ring D Analogues of the Pentacyclic Alkaloid Cephalotaxine by Two Palladium‐Catalyzed Reactions , 2000 .

[17]  K. Sharpless,et al.  Bromine-Catalyzed Aziridination of Olefins. A Rare Example of Atom-Transfer Redox Catalysis by a Main Group Element , 1998 .

[18]  T. Satoh.  Oxiranyl Anions and Aziridinyl Anions. , 1996, Chemical reviews.

[19]  R. Kavash,et al.  Two Interrelated Strategies for Cephalotaxine Synthesis. , 1996, The Journal of organic chemistry.

[20]  E. Doris,et al.  Regiospecific access to cyclic allylic alcohols by reductive alkylation of α-alkyloxy-epoxides , 1996 .

[21]  C. P. Yeh,et al.  A Friedel-Crafts cyclization approach toward cephalotaxine , 1991 .

[22]  P. Scola,et al.  Mitsunobu reactions of n-alkyl and n-acyl sulfonamides-an efficient route to protected amines , 1989 .

[23]  C. K. Lau,et al.  Five-membered ring annulation via thermal rearrangement of β-cyclopropyl α,β-unsaturated ketones. A formal total synthesis of the sesquiterpenoid (±)-zizaene , 1982 .

[24]  W. Agosta,et al.  Short synthesis of tricyclo[4.2.0.01,4]octanes , 1981 .