The Mechanisms of Stereoselective Michael Addition and Stereoselective Metallation yielding Z-and £-Lithio-3,3-l;>iphenylpropionylmesitylene

Equilibration of the Z -and £-lithium enolate isomers of 3,3-diphenylpropionylmesitylene, obtained via reactions (i) and (ii), respectively, has shown a gradual change in the E:Z ratio with the cation-solvating PhCH:CH·CO·Mes + Phli---+Ph 2 CH·CH:C(Oli) Mes (Z) ( i) (ii) ability of the medium from 95: 5 in ether to 18: 32 in 1 : 1 ether-HM PT (hexamethylphosphoric triamide). The kinetic E:Z ratio of metallation (ii) decreases, though less sensitively, in the same direction. Michael addition (i) yields the Z isomer under kinetic control regardless of the cation-solvating ability of the medium. According to i.r. and n.m.r. data, cinnamoylmesitylene prefers the s-trans conformation, which would lead to the E isomer in a fast Michael reaction, fixing the conformational equilibrium in the initial state. The formation of the Z isomer via reaction (i) is accounted for by the steric demands of the attack of phenyl-lithium in the transition state. The role of the cation association to the oxygen atom is discussed with respect to the equilibrium and kinetic results. isomer by metallation [equation · 6 Nesmeyanov et al. In this respect, it would be of interest to know to what extent Z-stereoselectivity is general for 1,4-addition and what kind of conditions are responsible for it. At this time there are few literature data available to answer these questions. Compared with 1,4-addition, the steric result of metallation of carbonyl compounds has received greater attention. Nesmeyanov et al

A normal gem-dimethyl effect in the base-catalyzed cyclization of -( p-nitrophenyl)hydantoic acids: evidence for hindered proton transfer in the permethylated esters †

The cyclization of hydantoic acids 2-UA and 3-UA -kinetics, solvent kinetic isotope effects (SKIE) and buffer catalysis -were studied in an attempt to explain the disappearance of the gem-dimethyl effect (GDME) in the specific base-catalyzed cyclization of hydantoic esters. pH-Rate profiles for both acids (after correction for ionization and for reversibility at high pH) show two regions of unit slope corresponding to different mechanisms. For 2-UA at high pH and 3-UA at lower pH the mechanism is considered to involve rate-determining attack by the ureido anion on the neutral carboxy group, consistent with the observed inverse SKIE. The normal GDME of 15 provides strong evidence that anomalies observed with the esters do indeed result from steric hindrance to proton transfer. The change to rate determining departure of OH Ϫ with 2-UA is caused at low pH by acid catalysis of the reversion of the tetrahedral intermediate (T Ϫ ) to reactants, while with 3-UA at high pH this takes place through T 2Ϫ . The GDME favours attack on the carboxylate anion but makes ring opening more difficult, thus decreasing acid inhibition. The observed β = 0.44 for general base catalysis of the cyclization of 2-UA is consistent with concerted deprotonation and attack of the ureido group. With 3-UA two simultaneous general base-catalyzed reactions take place: slow deprotonation of the ureido group (β = 1.0) and attack of the ureide anion on the carboxy anion aided by the buffer conjugate acid. The estimated GDME is 2800 for the equilibrium between acid anion and hydantoin, ‡ but only 45 and 15 for catalysis by H 3 O ϩ and OH Ϫ , respectively: both reactions are presumed to go through early transition states. A convenient way to accelerate the bioorganic reactions of small molecules is to introduce steric strain into the substrate. In cyclization reactions this is readily done by introducing substituents into the interconnecting chain: the resulting increase in rate defines the gem-dimethyl effect (GDME). 1 However, in a recent study 2,3 of catalytic mechanisms for the ring closure of hydantoic esters, we found no GDME for the base-catalyzed reaction. We concluded that the rate determining step had changed, for the most heavily substituted compounds, from the formation of the tetrahedral intermediate to its breakdown, because of steric hindrance in proton transfer to the leaving ethoxy group. In the tetrahedral intermediate, T Ϫ , the two methyl groups screen one side and the N-aryl substituent the other, while R (ethyl was studied) in its least hindered conformation blocks easy access of a general acid. If this analysis is correct, and the effect depends on steric hindrance in proton † Pseudo-first-order rate constants are available as supplementary data. For direct electronic access see http://www.rsc.org/suppdata/p2/b0/ b002276o ‡ The IUPAC name for hydantoin is imidazolidine-2,4-dione. transfer to the developing ethoxide by its ethyl group, it should be reduced or removed if a smaller group replaces ethyl. We have tested this proposition by studying the cyclization of the hydantoic acids shown in Scheme 1. We find that hydantoic acids 2 and 3 undergo base-catalyzed ring closure more slowly than the esters when the pH is higher than the pK of the COOH group; and that the results confirm our prediction. The hydroxide-catalyzed cyclization of the fully methylated acid 3-UA shows a normal GDME, and the solvent kinetic isotope effects (SKIE) suggest that acids 2-UA and 3-UA are cyclized by the same mechanism. Experimental Materials Inorganic reagents and buffer components were of analytical Scheme

Autoxidation of a 4-iminoimidazolidin-2-one with a tertiary 5-hydrogen to its 5-hydroxy derivative

Chemoselective autoxidation of 4-imino-1,5-dimethyl-3-(4-nitrophenyl) imidazolidin-2-one (1b) to its 5-hydroxy derivative 2 occurred in solutions of DMSO-d(6), acetonitrile-d(3) or refluxing ethanol. Also bis(imidazolidin-5-yl) peroxide 5 was isolated as a minor product. It crystallizes as a 1: 1 mixture of R*, R* and R*, S* diastereomers, whereas the NMR spectra of the reaction solution in DMSO-d(6) showed unequal amounts of the two isomers. Molecular mechanics modeling studies with the MM3 force field indicate the R*, S* diastereomer as the more stable one. The 5-unsubstituted and the 5,5-dimethyl substituted imines 1a and 1c, respectively, were found stable against autoxidation; the difference in reactivity of 1b is attributed to the single 5-methyl group enhancing the population of the enamine tautomer. The 5-hydroxy-4-imino-1,5-dimethylimidazolidin-2-one (2) underwent acid hydrolysis to form 5-hydroxyhydantoin 4