Intramolecular carbolithiation cascades as a route to a highly strained carbocyclic framework: competition between 5-exo-trig ring closure and proton transfer

• William F. Bailey and
• Justin D. Fair

Beilstein J. Org. Chem. 2013, 9, 537–543, doi:10.3762/bjoc.9.59

• [3.3.0.03,7]octane) framework by an intramolecular carbolithiation cascade involving three coupled 5-exo-trig cyclizations of the vinyllithium derived from 2-bromo-4-vinyl-1,6-heptadiene by lithium–bromine exchange was investigated. The cascade does not afford the stellane; rather, the cascade is terminated

• temperature. Keywords: carbolithiation cascade; carbometallation; intramolecular carbolithiation; intermolecular proton transfer; lithium–halogen exchange; strained hydrocarbons; Introduction The first publication describing an intramolecular carbolithiation appeared in 1968: Drozd and co-workers reported

• constructing a highly strained system by an intramolecular carbolithiation cascade involving three coupled 5-exo-trig cyclizations. Although many strained molecules could have been selected for this exploration, the stellane framework (tricyclo[3.3.0.03,7]octane [18][19]), 1, with its mesmerizing symmetry, was

Inter- and intramolecular enantioselective carbolithiation reactions

• Asier Gómez-SanJuan,
• Nuria Sotomayor and
• Esther Lete

Beilstein J. Org. Chem. 2013, 9, 313–322, doi:10.3762/bjoc.9.36

• , though it is beyond the scope of this review. Intramolecular carbolithiation reactions In the intramolecular carbolithiation of alkenes the highly reactive organolithium species has to be selectively generated in the presence of the internal alkene. Several approaches have been used for this purpose

• , such as halogen–lithium exchange, tin–lithium exchange, selenium–lithium exchange or reductive lithiation [1][2][3][4][5][6][7][8]. Once the organolithium has been generated, the intramolecular carbolithiation reaction usually takes place with high stereochemical control, as a consequence of a rigid

• , the internally coordinated organolithium would have two additional sites available for coordination with a chiral bidentate ligand. Thus, enantioselective versions of intramolecular carbolithiation reactions can also be carried out under the influence of a chiral ligand for lithium (Scheme 9). However

Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan

• Wafa Gati,
• Mohamed M. Rammah,
• Mohamed B. Rammah and
• Gwilherm Evano

Beilstein J. Org. Chem. 2012, 8, 2214–2222, doi:10.3762/bjoc.8.250

• 10.3762/bjoc.8.250 Abstract We have developed a general synthesis of polysubstituted 1,4-dihydropyridines and pyridines based on a highly regioselective lithiation/6-endo-dig intramolecular carbolithiation from readily available N-allyl-ynamides. This reaction, which has been successfully applied to the

• formal synthesis of the anti-dyskinesia agent sarizotan. Results and Discussion Feasibility of the deprotonation/intramolecular carbolithiation To first evaluate the compatibility of the ynamide moiety with the lithiation step and address potential problems associated with competitive carbolithiation of

• , therefore demonstrating the compatibility of the ynamide group with the deprotonation step (Scheme 2a), although longer reaction times before the addition of methyl iodide resulted in much lower yields and extensive degradation: The intramolecular carbolithiation of N-allyl-ynamides to 1,4-dihydropyridines