Enantioselective Synthesis of 3,3-Disubstituted Indolines via Asymmetric Intramolecular Carbolithiation in the Presence of (-)-Sparteine

Abstract

The functionalized N-benzyl-protected bromoanilines underwent an asymmetric intramolecular carbolithiation in the presence of t-BuLi and (-)-sparteine yielding 3,3-disubstituted indolines.

Inter- and intramolecular enantioselective carbolithiation reactions

“…Substituted alkenes may also be used in these reactions, and 3,3-disubstituted indolines 42 are obtained in moderate to high enantiomeric excesses, depending on the nature of the substituent on the alkene (Scheme 15) [49]. The steric demand of an isopropyl group increases the enantioselectivity in the cyclization of 42a (Scheme 15), though the reaction fails with a phenyl substituent ( 42b ).…”

Highly Enantioselective (−)-Sparteine-Mediated Lateral Metalation-Functionalization of Remote Silyl Protected ortho-Ethyl N,N-Dialkyl Aryl O-Carbamates

“…Since the original work of Nozaki and Guetté 4 decades ago and the pioneering contributions of the groups of Hoppe − and, subsequently, Beak, the application of the enantiopure lupine alkaloid (−)-sparteine as an additive in “carbanionic” enantioselective synthesis has gained considerable prominence. Thus, the broad scope of (−)-sparteine-mediated carbanionic transformations ,, has been demonstrated, inter alia , in the preparation of enantioenriched natural and unnatural amino acids, asymmetric inter- and intramolecular carbolithiations, an enantioselective Li-ene-reaction, the enantioselective preparation of functionalized 1,5-cyclononadienes and anti homoaldol products, enantioselective functionalization of small and medium-sized rings, the generation of P-stereogenic centers, and the enantioselective lithiation of unsaturated carbamates …”

Intramolecular Carbolithiation Reactions for the Synthesis of 2,4-Disubstituted Tetrahydro-quinolines: Evaluation of TMEDA and (−)-Sparteine as Ligands in the Stereoselectivity † Dedicated to Prof. Josep Font on the occasion of his 70th birthday.

“…Although many of these carbolithiations involve alkyl or alkenyllithiums, there are also some examples of cycloisomerization of alkenyl substituted aryllithiums generated by metal−halogen exchange . Thus, an intramolecular carbolithiation reaction of unsaturated aryllithiums is particularly well suited for the construction of five-membered rings through a 5- exo -trig cyclization process, as it has been shown in the synthesis of carbocyclic and heterocyclic compounds, even in a diastereoselective or enantioselective fashion. , However, some limitations have precluded the general applicability of this method. In fact, the above-cited examples consist of intramolecular carbolithiations to five-membered rings and it remains unclear whether cyclization to six-membered cycles would provide the same degree of stereo- and regiochemical efficiency.…”