Efficiency kinetics

An efficient kinetic resolution of racemic secondary allyl carbamates was accomplished by the jw-butyllithium-(-)-sparteine complex76 131. Whereas the R-enantiomer (80% ee) is recovered unchanged, the 5-enantiomer is deprotonated preferentially. 

The physical properties of the mobile phase, mainly viscosity, diffusivity and solubility, affect the flow characteristics, column efficiency (kinetics), and retention (thermodynamics) in the chromatographic process. These physical properties are affected by temperature. Chromatographic techniques, although basically simple in... 

An efficient kinetic resolution of 4-hydroxy-2-cyclopentenone was achieved using [kh((/ )-UINAI))(CIIjOHl JCKT as catalyst.1 The reaction proceeded with a 5 1 discrimination rate between the two enantiomers, and (.S l-isoincr, which is a useful intermediate in prostaglandin synthesis, was obtained with 91% ee at 72% conversion (Scheme 31).54... 

In the case of acyclic allylic alcohols, an efficient kinetic resolution of l-buten-3-ol was achieved using [Ru((7 )-BINAP)(H)(CH3CN)(THF)2]BF4 as catalyst (Equation (16)).55... 

M. Tokunaga, J. F. Larrow, F. Kakiuchi, E. N. Jacobsen, Asymmetric Catalysis with Water Efficient Kinetic Resolution of Terminal Epoxides by Means of Catalytic Hydrolysis, Science 1997, 2T7, 936-938, and references cited therein. 

High-pressure liquid chromatographic (HPLC) analysis performed with a chiral mobile phase (57,58) confirmed in all the conglomerate systems that the S inhibitors are selectively occluded only in the bulk of the S substrate crystals, typically in amounts of 0.5-1% (and, by symmetry, occlusion of R occurs only in R crystals). The selective adsorption causes, furthermore, a drastic decrease in the growth (and possibly nucleation) rate of the affected enantiomer, leading to efficient kinetic resolution various conglomerate systems have been resolved by this method (54). 

Recently, Juge and Kagan (68) reported that a more efficient kinetic resolution of racemic sulfoxides takes place in the Pummerer-type reaction with optically active a-phenylbutyric acid chloride 38 in the presence of N,A-dimethylaniline. In contrast to the asym-... 

Tokimaga, M. Larrow, J. F. Kakiuchi, F. Jacobsen E. N. (1997) Asymmetric catalysis with water Efficient kinetic resolution of terminal epoxides by means of catalytic hydrolysis., Science, 111 936-938. 

Efficient kinetic resolntion was also observed dnring the deprotonation of the carbamates rac-91 and rac-100. Eqnation 21 shows the preferred prodncts [(2/()-98 and (25)-101] obtained from the racemates with recovery of the enantiomerically enriched starting materials (5 )-97 and (2/()-100 . Diastereomer (25 )-99 arises in low yield but high ee. Even simple PM3 calculations reflect the experimentally recorded (opposite) diastereoselectivities well . ... 

An efficient kinetic resolution was also observed during the (—)-sparteine-mediated deprotonation of the piperidin-2-yhnethyl carbamate rac-112 (equation 25). By treatment of rac-112 with s-BuLi/(—)-sparteine (11), the pro-S proton in (/ )-112 is removed preferentially to form the lithium compound 113, which undergoes intramolecular cyclo-carbolithiation, and the indolizidinyl-benzyllithium intermediate 114 was trapped with several electrophiles. The mismatched combination in the deprotonation of (5 )-112, leading to cp/-113, does not significantly contribute to product formation. Under optimized conditions [0.75 equivalents of s-BuLi, 0.8 equivalents of (—)-sparteine, 22 h at —78°C in diethyl ether] the indolizidine 115 was isolated with 34% yield (based on rac-112), d.r. = 98 2, e.r. = 97 3 optically active (5 )-112 was recovered (46%, 63% ee). 

When the racemic carbamate 299b is deprotonated by 0.5 equivalents of w-BuLi/(—)-sparteine (11), an efficient kinetic resolution takes place to produce the lithium compound (5)-300b (80-82% ee) and leaving (R)-299b (80% ee) behind (equation 75)9.219,221-223... 

It has been demonstrated by Pancrazi, Ardisson and coworkers that an efficient kinetic resolution takes place when an excess (2 equivalents) of the racemic titanated alkenyl carbamate rac-334a (R = Me) is allowed to react with the enantiopure )-hydroxyaldehyde 341 or alternatively the corresponding y-lactol 340, since the mismatched pair contributes to a lower extent to the product ratio (equation 91) . Under best conditions, the ratio of the enantiomerically pure diastereomers 3,4-anti-4,5-syn (342) and 3,4-anti-4,5-anti (343) is close to 14 1. Surprisingly, approximately 9% of the iyw,iyw-diastereomer 344 resulted when the starting (ii)-crotyl carbamate was contaminated by the (Z)-isomer. The reasons which apply here are unknown. Extra base has to be used in order to neutrafize the free hydroxy group. The pure awft, awfi-product 345 was obtained with 85% yield from the reaction of the (W-oxy-substituted titanate rac-334b and lactol 340. 345 is an intermediate in the asymmetric synthesis of tylosine . ... 

Efficient kinetic resolution of chiral unsaturated secondary alcohols by irreversible enzyme-mediated acylation (with vinyl acetate as acylating agent, a crude preparation of Pseudomonas AK, and hexane as solvent) is possible, provided one relatively large and one small substituent are attached to the carbinol carbon. However, the method can be used to resolve substrates that are not amenable to asymmetric epoxidation (see examples 23, 25, 27, 29, where the double bond is either deactivated by an electron-withdrawing substituent, or is of the propargyl alcohol type). Acylation of the / -enantiomer consistently proceeds faster than that of the 5-enantiomer. An example of an allenic alcohol was also reported248. 

In the reaction of the eight-membered cyclic carbonate rac-lca with KSAc in THF/H2O (see Scheme 2.1.4.21) the conversion of the substrate, even at higher temperatures, did not exceed 53% and gave a mixture of thioacetate 19aa and carbonate ent-lca in a ratio of 53 47. Formation of thioacetate 19aa with 84% ee and of carbonate ent-lca with 72% ee in a ratio of approximately 1 1 (Table 2.1.4.15, entry 1) showed that an efficient kinetic resolution had occurred (see Scheme 2.1.4.21). Similar results were recorded in the reaction of carbonate rac-lca with KSBz (entry 2). The results recorded after the termination of the reaction of the acyclic carbonate rac-3ba with KSBz in CH2CI2/H2O at 48% conversion also revealed the operation of kinetic resolution in this case (entry 3). 

A similar efficient kinetic resolution took place in the reaction of the cyclohep-tenyl acetate roc-lbb with KSAc. The reaction came to a practically complete halt at 51% conversion of the substrate. The acetate mt-lbb was obtained with >99% ee in 48% yield and the thioacetate 19ba was isolated with 98% ee in 50% yield (entry 9, Table 2.1.4.15). Even an increase in the amount of Pd(0)/L from 2 to... 

P. L. Barili, G. Berti, G. Catelani, F. Colonna, and E. Mastrorilli, Alkaline and enzymatic hydrolysis of isobutyl 3,4-anhydro-2,6-dideoxy-DL-hexopyranosides. Preparation of enantiomeric boivinopyranosides through a highly efficient kinetic resolution, J. Org. Chem., 52 (1987) 2886-2892. 

As mentioned above for the preparation of thioamides, the reaction of di-thioesters with amines is generally rapid and efficient. Kinetics have shown [153] that this reaction involves two molecules of amine and consists of the following events nucleophilic addition, amine assisted prototropy and decomposition of the neutral tetrahedral intermediate. This study was undertaken with a view to polythioamide synthesis. 

A complete study concerning a new class of supramolecular structures (supraminols) has been recently published. These supramolecular structures are formed by an enantiodifferentiating self-assembly between (If , 2f )-diaminocyclohexane and various trans-1,2-cyclohexane diols. An example is shown in eq 27. When racemic diols were used, a homochiral cristalline adduct is formed with an efficient kinetic resolution. 

A second example of the allylboration of a metal carbonyl containing substrate is a highly group- and face-selective allylboration of a meso iron-diene dialdehyde complex (eq 6). Efficient kinetic resolutions of racemic diene aldehyde-Fe(CO)3 complexes have also been demonstrated. ... 

The asymmetric glyoxylate-ene reactions have been exploited in the total synthesis of (—)-specionin, which involves asymmetric desymmetrization of a prochiral diene (eq 3), and (—)-xylomollin, which involves an efficient kinetic resolution of a racemic diene (eq4).i - ... 

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