Carbolithiation of N-alkenyl ureas and N-alkenyl carbamates

• Julien Lefranc,
• Alberto Minassi and
• Jonathan Clayden

Beilstein J. Org. Chem. 2013, 9, 628–632, doi:10.3762/bjoc.9.70

• incorporating an α-aryl substituent, we show that they will also undergo attack at the β-carbon by organolithium nucleophiles, leading to the products of carbolithiation. The carbolithiation of E and Z N-alkenyl ureas is diastereospecific, and N-tert-butoxycarbonyl N-alkenyl carbamates give carbolithiation

• products that may be deprotected in situ to provide a new connective route to hindered amines. Keywords: carbamate; carbolithiation; carbometallation; organolithium; stereospecificity; styrene; urea; Introduction Enamines and N-acyl enamines are in general nucleophiles, reacting with electrophiles at the

• in an enamine carbolithiation reaction [9]. Similar reactivity is observed with related O-carbamoyl enols [10][11][12]. The organolithium resulting from the enamine carbolithiation is nucleophilic at the atom α to nitrogen, and such carbolithiations have been used to generate hindered organolithiums

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

• inter- and intramolecular enantioselective carbolithiation reactions carried out in the presence of a chiral ligand for lithium, such as (−)-sparteine, to promote facial selection on a C=C bond. This is an attractive approach for the construction of new carbon–carbon bonds in an asymmetric fashion, with

• the possibility of introducing further functionalization on the molecule by trapping the reactive organolithium intermediates with electrophiles. Keywords: alkenes; asymmetric synthesis; carbolithiation; carbometallation; enantioselectivity; lithium; Introduction The carbolithiation reaction has

• chiral ligands for lithium, thus opening new opportunities for their application in asymmetric synthesis. The naturally occurring alkaloid (−)-sparteine, which has been until recently inexpensive and commercially available, is the most widely used chiral ligand in enantioselective carbolithiation

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, further extends the use of ynamides in organic synthesis and further demonstrates the synthetic efficiency of carbometallation reactions. Keywords: carbolithiation; carbometallation; dihydropyridines; organolithium reagents; pyridines; sarizotan

• carbolithiation of ynamides, which may provide an interesting entry to highly functionalized 1,4-dihydropyridines [27][28][29] and pyridines [30][31][32][33], most useful building blocks in organic synthesis and medicinal chemistry as well. Our strategy is summarized in Scheme 1 and is based on the following

Asymmetric synthesis of tertiary thiols and thioethers

• Jonathan Clayden and
• Paul MacLellan

Beilstein J. Org. Chem. 2011, 7, 582–595, doi:10.3762/bjoc.7.68

• arylation (by rearrangement) of thiocarbamates offering the best prospects. Further developments in this area – particularly with regard to carbolithiation reactions [79] – are to be expected. Seven out of the ten top selling drugs in the USA in 2009 contain sulfur. Figures in italics are total retail sales