Enantioselectivity organolithium cyclization

It should also be noted that the 5-exo-trig cyclization of achiral olefinic organolithiums has been found to proceed enantioselectively when conducted in the presence of a chiral ligand that serves to render the lithium atom stereogenic. Thus, for example, R) 1 -allyl-3-methylindolinc has been prepared in 86 % ee by cyclization of an achiral aryllithium in the presence of an equivalent of (-)-sparteine.15... 

The chiral base i-BuLi/(—)-sparteine enantioselectively deprotonates the benzylic position of Ai-Boc-3-chloropropyl carbamates, which then cyclize to yield 2-substituted pyrrolidines with enantiomeric ratios greater than 90 10 (Scheme 63). Beak and coworkers showed that enantioselectivity is achieved through an asymmetric deprotonation to give an enantioenriched organolithium intermediate, which undergoes cyclization faster than epimerization. 

An enantioselective method for the synthesis of 3-functionalized 2,3-dihydrobenzofuran derivatives via an intramolecular carbolithiation reaction of allyl 2-lithioaryl ethers uses (—)-sparteine as a chiral inductor. A variety of electrophiles can be reacted with the cyclized organolithium intermediate. With certain substrates, however, /3-elimination occurs instead (Equation 140) <2005CEJ5397>. 

Enamines of cyclohexylamine have been enantioselectively cyclized to bicyclo[3.3.1] nonanedione systems, using acryloyl chloride and chiral pyrrolidine catalysis. Enantio-pure A-sulflnylimines have been used in asymmetric synthesis of isoquinolone alkaloids, and a stereocontrolled synthesis of 3,4,5,6-tetrahydropyrimidine-based amino acids from imino ethers has been reported. Diastereoselective additions of chiral acetals of (2-lithiophenyl)acetaldehyde to arylimines have been used in an asymmetric synthesis of 1-aryltetrahydroisoquinolines. " Organolithiums react with chiral imines, in the presence of Lewis acids or bases, to give amines in up to 100% de. Diastereoselective additions of copper reagents to imines derived from (5)-l-phenylethylamine have been reported. 

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