Acetals kinetic control

Protonation of the a-carbanion (50), which is formed both in the reduction of enones and ketol acetates, probably first affords the neutral enol and is followed by its ketonization. Zimmerman has discussed the stereochemistry of the ketonization of enols and has shown that in eertain cases steric factors may lead to kinetically controlled formation of the thermodynamically less stable ketone isomer. Steroidal unsaturated ketones and ketol acetates that could form epimeric products at the a-carbon atom appear to yield the thermodynamically stable isomers. In most of the cases reported, however, equilibration might have occurred during isolation of the products so that definitive conclusions are not possible. 

The positions of substitution, orientation, and configuration of the stable form are determined by a balance between opposing steric and dipole ef-fects. There is less agreement regarding the factors influencing kinetically controlled reaction (see below). Essentially neutral conditions, such as provided by an acetate or pyridine buffer, are required to avoid isomerization. Frequently, however, bromination will not proceed under these conditions, and a compromise has been used in which a small amount of acid is added to start and maintain reaction, while the accumulation of hydrogen bromide is prevented by adding exactly one equivalent of acetate... 

A commonly used alternative to the direct bromination of ketones is the halogenation of enol acetates. This can be carried out under basic conditions if necessary. Sodium acetate, pyridine or an epoxide is usually added to buffer the reaction mixture. The direction of enolization is again dependent upon considerations of thermodynamic and kinetic control therefore, the proportion of enol acetates formed can vary markedly with the reaction conditions. Furthermore, halogenation via enol acetates does not necessarily give the same products as direct halogenation of ketones 3. 23... 

In the absence of steric factors e.g. 5 ), the attack is antiparallel (A) (to the adjacent axial bond) and gives the axially substituted chair form (12). In the presence of steric hindrance to attack in the preferred fashion, approach is parallel (P), from the opposite side, and the true kinetic product is the axially substituted boat form (13). This normally undergoes an immediate conformational flip to the equatorial chair form (14) which is isolated as the kinetic product. The effect of such factors is exemplified in the behavior of 3-ketones. Thus, kinetically controlled bromination of 5a-cholestan-3-one (enol acetate) yields the 2a-epimer, (15), which is also the stable form. The presence of a 5a-substituent counteracts the steric effect of the 10-methyl group and results in the formation of the unstable 2l5-(axial)halo ketone... 

The exocyclic C — C double bond in the chlorin can be reduced by catalytic hydrogenation in tetrahydrofuran/water in the presence of palladium(II) acetate with triethoxysilane as hydrogen source to yield under kinetic control cw-stereoisomers, which can be transformed by treatment with /)-toluenesulfonic acid in methanol to the thermodynamically favored trans-isomers.27d... 

High enantioselectivities may be reached using the kinetic controlled Michael addition of achiral tin enolates, prepared in situ, to a,/i-unsaturated carbonyl compounds catalyzed by a chiral amine. The presence of trimethylsilyl trifluoromethanesulfonate as an activator is required in these reactions236. Some typical results, using stoichiometric amounts of chiral amine and various enolates are given below. In the case of the l-(melhylthio)-l-[(trimethylsilyl)thio]ethene it is proposed that metal exchange between the tin(II) trifluoromethanesulfonate and the ketene acetal occurs prior to the 1,4-addition237,395. 

The Pummerer reaction346 of conformationally rigid 4-aryl-substituted thiane oxides with acetic anhydride was either stereoselective or stereospecific, and the rearrangement is mainly intermolecular, while the rate-determining step appears to be the E2 1,2-elimination of acetic acid from the acetoxysulfonium intermediates formed in the initial acetylation of the sulfoxide. The thermodynamically controlled product is the axial acetoxy isomer, while the kinetically controlled product is the equatorial isomer that is preferentially formed due to the facile access of the acetate to the equatorial position347. The overall mechanism is illustrated in equation 129. 

The penicillin-N,S-acetal 479 reacts with N,N-bis(trimethylsilyl)formamide 22c and Hg(OAc)2, apparently via the iminium salt 480, to give the penicillin-N,N-acetal 481 in 65% yield [64]. On treatment of racemic y-ketoesters such as 482 with chiral silylated 1,3-mercaptoalcohols such as 483, in the presence of TMSOTf 20, at room temperature a kinetically controlled 2 1 mixture of the 0,S-acetals... 

In order to estimate the branching factor e for polyvinyl acetate we have analyzed the SEC data obtained on sample PVAc-E4 using the MWBD method with various e values. This sample was synthesized under kinetically controlled conditions (isothermal, T = 60°C, [AIBN] = 10"5 g-mole/1, conversion level of 48.5 percent). The SEC measurements were made at 25°C in tetrahydro-furan. The Mark-Houwink coefficients used for linear polyvinyl acetate are those suggested by Graessley (21), namely K = 5.1 x 10"5 dl/gm and a = 0.791. The whole polymer M, Mj, and B j values obtained are listed in Table II. 

S-D-Xylosidase in extract from Trichoderma reesei Transxylosylation with methyl-/i-xyloside and 1 -butanol Butanol-acetate buffer pH 4.5 Kinetically controlled process 128... 

This procedure illustrates a fundamentally new method for constructing substituted tetrahydrofurans.5-10 This practical method assembles the tetrahydrofuran ring from allylic diol and carbonyl components and in the process forms three ring bonds C(2)-C(3), C(4)-C(5) and 0-C(5). Both aldehydes (eq 1) and ketones (illustrated in the present procedure) can be employed as the carbonyl component. Although it is often convenient to isolate the acetal intermediate, conversion to the 3-acyltstrahydrofuran can also be accomplished in many cases by the direct reaction of the diol and carbonyl components.8 High ds stereoselectivity (at least 20 1) is observed in the preparation of tetrahydrofurans that contain single side chains at carbons 2 and 5 (eq 1). The kinetically controlled product also has the cis relationship of these side chains and the 3-acyl substituent. 

Silyloxy)alkenes were first reported by Mukaiyama as the requisite latent enolate equivalent to react with aldehydes in the presence of Lewis acid activators. This process is now referred to as the Mukaiyama aldol reaction (Scheme 3-12). In the presence of Lewis acid, anti-aldol condensation products can be obtained in most cases via the reaction of aldehydes and silyl ketene acetals generated from propionates under kinetic control. 

Pikho and co-workers50 found that nonanomeric [6,5]-spiroketals (having a pyranoside moiety with an equatorial CO acetal bond) can be formed under conditions of kinetic control. For instance, 62 undergoes acid catalyzed spiroacetalization giving the anomeric (most stable) acetal 63... 

It has therefore been established170 from the product distributions that, while the oxymercuration is reversible, unless a base (e.g. sodium acetate) is added to the reaction medium, and gives almost exclusively the more stable compound 199, the aminomercu-ration takes place to give the kinetically controlled adduct 200, or under thermodynamic control the aminomercurial 201. Reactions are kinetically controlled when the mercurating species is a mercury(II) salt deriving from a weak acid such as mercury(II) acetate. Conversely, they are thermodynamically controlled with the covalent mercury(II) chloride. In the latter case, the presence of a strong acid in the medium allows the thermodynamically controlled product to be obtained. 

The opening of the epoxide in the cij-decalin 24 by acetic acid leads exclusively to the hydroxyacetate 25 (through a kinetically controlled rrani-diaxial opening) rather than to the wanted diastereomer 26 (c/ the stereochemistry of the "southern" part of reserpine). To obtain the correct diastereomer the epoxy-lactone 22 is first formed (Scheme 8.6). Thus the conformation of the cij-decalin system, and therefore that of the substituents, is reversed. The kinetic tran -diaxial opening of the epoxide occurs in a regio- and stereoselective manner to afford compound 28 in which the substituents have the correct position and configuration (a-OH, P-OAc),... 

It has been demonstrated that organotin-mediated multiple carbohydrate esterifications can be controlled by the acytaring reagent and the solvent polarity. When acetyl chloride is used, the reactions are under thermodynamic control, whereas when acetic anhydride is employed, kinetic control takes place. Very good selectivity can furthermore be obtained in more polar solvents. These results can be used in the efficient preparation of prototype carbohydrate structures. 

In contrast, electrophilic additions to the double bond of acetal 70 (derived from 64 ) gave adduct mixtures 71/72 with regioselectivities opposite to those of reactions 64 + EX — 68 + 69, 72 being the major adducts. Tests were carried out to confirm that adducts 68 + 69 and 71+72 were formed under conditions of kinetic control. Acetal 70 was obtained optically pure via resolution of lactol 73 by medium pressure chromatographic (silica gel) separation of the diastereomeric acetals 74 derived from (-)-menthol. ... 

The type of solvent can affect the kinetics, and, as a consequence, the equilibrium is sometimes not reached within a reasonable time. For example, Kim and Shin studied the kinetically controlled synthesis of alitame precursor (Z-Asp(OEt)-D-Ala-NH2), and better results were obtained in the presence of dimethyl sulfoxide and 2-methoxyethyl acetate as adjuvants. These solvents promoted product precipitation while maintaining the reaction mixture in a homogeneous state, thus improving the conversion [64]. 

In acetonitrile, 237 and 238 are reduced in two one-electron steps through the anion-radical to the dianion in the presence of acetic anhydride, 238 forms a mixture of 1,2-diacetyl-1,2-dihydro-3-phenylpyrido[3,4-e]-as-tria-zine (239) and the 1,4-diacetyl-1,4-dihydro derivative (240). On heating of the kinetically controlled product, 239 rearranges to the thermodynamically more stable 240.37°... 

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