Synthesis of New Chiral Derivatives of N,N′-Dimethylpropyleneurea (DMPU) and Examination of Their Influence on the Regio- and Enantioselectivity of Addition of 2-(1,3-Dithianyl)lithium to Cyclohex-2-en-1-one

Abstract

The preparation of three new chiral derivatives of DMPU (N,N'-dimethylpropyleneurea) is described (Schemes 2 ± 4); 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-ionpair (SSIP) formation; this was confirmed by PM3 and B3LYP/3-21-G(d)//PM3 calculations (Scheme 6).

New Chiral N‐Heterocyclic Carbene Ligands in Palladium‐Catalyzed α‐Arylations of Amides: Conformational Locking through Allylic Strain as a Device for Stereocontrol

“…The six‐membered N‐heterocycle product ( R , R )‐ 5 m was synthesized by a four‐step procedure (Scheme ) 29. Treatment of ( R )‐ 1 c with acrolein and subsequent in situ reduction gave the 1,3‐diamine; cyclization by treatment with NH 4 BF 4 and HC(OEt) 3 , followed by anion metathesis with NaI, afforded ( R , R )‐ 5 m in 70 % yield.…”

Conjugate Additions to Phenylglycinol-Derived Unsaturated δ-Lactams. Enantioselective Synthesis of Uleine Alkaloids

“…Taking into account that metalated dithioacetals have been reported to undergo conjugated addition reactions to unsaturated amides and lactams in fair yields, , we decided to investigate the introduction of the required indolylmethyl substituent on the 4 position of the piperidine ring of lactam 10 by conjugate addition of a 2-(2-indolyl)-1,3-dithiane derivative. It should be mentioned that, although much effort has been devoted to identifying the factors governing the regioselectivity in the addition of sulfur-stabilized anions to enones, there are few reports concerning the stereoselectivity of such conjugate addition reactions 19e. For this reason, we became interested in studying the stereochemical outcome of the conjugate addition of a variety of dithioacetals to phenylglycinol-derived unsaturated lactams as a tool for the enantioselective generation of cis or trans 3,4-disubstituted piperidine derivatives.…”

Novel Perfluoroalkyl-Diphenylphosphine Compounds. Syntheses and Reaction Mechanisms

“…To avoid the inherent toxicity related to the use of HMPA solutions, we undertook the nucleophilic substitution reactions of R f I with PPh 2 - ions in DMPU − as solvent. The Ph 2 P - ion was generated by allowing PPh 3 and sodium metal to react under ultrasound conditions.…”