E. Juaristi, M. Hernandez-Rodriguez, Heraclio López-Ruiz, J. Aviña, O. Muños-Muniz, M. Hayakawa, D. Seebach. Synthesis of New Chiral Derivatives of N,N-Dimethylpropyleneurea (DMPU) and Examination of Their Influence of the Regio- and Enentioselective of Addition of 2(1,3Dithianyl)lithium to Cyclohex-2-en-one. Helvetica Chimica Acta, 85, 1999-2007 (2002). DOI: 10.1002/1522-2675(200207)85:7<1999::AID-HLCA1999>3.0.CO;2-K
The preparation of three new chiral derivatives of DMPU (N,N?-dimethylpropyleneurea) is described (Schemes?24); one type of derivative carries 1-phenylethyl or 1-cyclohexylethyl groups at the N-atoms of the tetrahydropyrimidin-2(1H)-one ring (2 and 4), another type of derivative is substituted at C(4) and C(6) of the heterocyclic ring (7). The potential of these chiral Lewis bases as promoters in the regio- and/or enantioselective addition of 2-(1,3-dithianyl)lithium to cyclohex-2-en-1-one was explored; they are all unable to effect enantioselective addition; the derivatives with branched substituents at the N-atoms do not shift the addition mode from 1,2 to 1,4, while the 3,4,5,6-tetrahydro-1,3,4,6-tetramethylpyrimidin-2(1H)-one does (Scheme?5). The results provide useful information regarding the nature of the nucleophilic organolithium reagent: obviously, the steric hindrance to Li complexation on the CO O-atom of the tetrahydropyrimidin-2(1H)-one by branched substituents at N-atoms (cf. X-ray crystal structure of 2 in the Fig.) prevents solvent-separated-ion-pair (SSIP) formation; this was confirmed by PM3 and B3LYP/3-21-G(d)//PM3 calculations (Scheme?6).