Solvent effects Michael

Similar additions may be performed with the enamine 13. However, with 3-buten-2-one or methyl 2-propenoate Lewis acid catalysis is needed to activate the Michael acceptor chloro-trimethylsilane proved to be best suited for this purpose. A remarkable solvent effect is seen in these reactions. A change from THF to HMPA/toluene (1 1) results in a reversal of the absolute configuration of the product 14, presumably due to a ligand effect of HMPA235. 

Besides formaldehyde, Michael acceptors such as acrylonitrile and ethyl acrylate also serve as substrate to undergo the addition in the presence of various metal complexes [10-14]. Acrylonitrile affords P(CH2CH2CN)3 tcep (Scheme 3). The order of catalytic activity is reported to be Pt[P(CH2CH2CN)3]3>Pd[P(CH2CH2CN)3]3P IrCl[P(CH2CH2CN)3]3>Ni[P(C-H2CH2CN)3]3. The solvent effect on the rate is not significant. In acetonitrile, however, a small amount of a telomer is formed. 

Fe(III)-exchanged fluorotetrasilicic mica acts as a highly effective and reusable catalyst for solvent-free Michael reactions of P-oxo esters with MVK (41a). The immobilized catalyst shows higher activity than homogenous Fe(III) catalysts. Product 42a (cf. Scheme 8.27), for example, is formed in 99% yield even if the catalyst is reused four times [92]. 

Tanaka, T. Kumanoto, T. Ishikawa, T. Solvent effects on stereoselectivity in 2,3-dimethyM- chromanone cyclization by quinine-catalyzed asymmetric intromolecular oxo-Michael addition. Tetrahedron-Asymmetry, 2000, 11 4633 637. 

A soln. of 2-carbomethoxy-2-cyclohexenone in chloroform added during 25 min to a mixture of startg. p-ketoester and 0.47 eqs. CS2CO3 in the same solvent at room temp., 2.5 h later CS2CO3 removed, and the crude product refluxed with / -TsOH in benzene product. Y 70% (99.5% cis-cis isomer). Solvent effects and reaction mechanisms s. P. Deslongchamps, J.-F. Lavallee, Tetrahedron Letters 29, 5117-8 (1988) 14a-hydroxysteroids by sequential Michael addition-intramolecular aldol condensation s. ibid. 6033-6. 

Kinetic studies of Michael addition of alicyclic secondary amines to ethyl propiolate in H2O and MeCN have demonstrated a substantial solvent effect on reactivity and transition-state structure. The amines were found to be less reactive in MeCN, although they are by 7-9 units more basic in the aprotic solvent. The reaction rates for morpholine and deuterated morpholine proved to be identical, which rules out both a stepwise mechanism in which proton transfer would occur in the RLS and a concerted mechanism in which nucleophilic attack and proton transfer would occur through a four-membered cyclic transition state. Consequently, a stepwise mechanism with proton transfer occurring after the RLS is probable. Br0nsted-type plots were found to be linear with = 0.29 and 0.51 in H2O and MeCN, respectively, indicating that bond formation is not advanced significantly in the RLS. The small value is also consistent with the absence of isotope effect. ... 

Kobayashi and coworkers further developed a new immobilizing technique for metal catalysts, a PI method [58-61]. They originally used the technique for palladium catalysts, and then applied it to Lewis acids. The PI method was successfully used for the preparation of immobilized Sc(OTf)3. When copolymer (122) was used for the microencapsulation of Sc(OTf)3, remarkable solvent effects were observed. Random aggregation of copolymer (122)-Sc(OTf)3 was obtained in toluene, which was named as polymer incarcerated (PI) Sc(OTf)3. On the other hand, spherical micelles were formed in THF-cyclohexane, which was named polymer-micelle incarcerated (PMI) Sc(OTf)3.. PMI Sc(OTf)3 worked well in the Mukaiyama-aldol reaction of benzaldehyde with (123) and showed higher catalytic activity compared to that of PI Sc(OTf)3 mainly due to its larger surface area of PMI Sc(OTf)3. This catalyst was also used in other reactions such as Mannich-type (123) and (125) and Michael (127) and (128) reactions. For Michael reactions, inorganic support such as montmorilonite-enwrapped Scandium is also an efficient catalyst [62]. 

Finally, Seebach has used the cyclic urea (69), DMPU, as a co-solvent in double lithiations, oxirane ring-opening, Wittig reactions, Michael additions of lithiated dithianes to cycloalkenones, and the selective generation of enolates." The interesting point here is that DMPU exhibits the same solvent effect as the carcinogen HMPA and might therefore be a safe substitute. 

Ab initio MO calculations indicate that the cyclopropanation of methylidenemalono-nitriles (380) with the ylide generated from the Krohnke a-pyridiniumacetates (379) in gas phase proceeds with the final formation of (381) as the rate-determining step. On the other hand, solvent effect approximations imply that rate determining in water is the initial Michael addition, generating the di-configured intermediate. ... 

For the Michael addition between 3-pentanone and nitrostyrene a report by Patil and Sunoj points out a key limitation of the standard enamine derived transition state model when a polar protic reaction medium is employed (Scheme 17.10) [42]. The unassisted transition state inclusive of continuum solvent effects failed to predict the correct stereochemical outcome of the reaction as compared to the experimental observations. The predicted lowest energy transition state has been identified as leading to an incorrect configuration of the newly formed chiral centers as well as the wrong diastereomer. Further refinements to the transition state models were carried out with inclusion of explicit solvent molecules in view of the fact that the reaction being modeled has been conducted in methanol as the solvent. After examining several microsolvated transition states with varying... 

The solvent and temperature effects for the Michael addition of amidoxime 7 to DMAD were probed because the reaction itself occurs without any other catalysts. As shown in Table 6.2, the reaction gave a high ratio of 8E in strongly aprotic polar solvents such as DMF and DMSO (entry 1 and 2). 8E was also found as the major product in MeCN (entry 3), dichloromethane (entry 4), and xylenes (entry 5). To our delight, the desired 8Z was obtained as the major component in methanol (entry 6). The stereoselectivity of 8Z versus 8E was better at low temperature (entry 7). A similar result was observed when the reaction was run in THF or dichlo-roethane in the presence of a catalytic amount of DABCO (entries 9 and 10). 

Classical C,C-coupling reactions of AN anions (Henry, Michael, and Mannich) involve complex systems of equilibria and, consequently, generally not performed in protic solvents. The introduction of the silyl protecting group allows one to perform these reactions in an aprotic medium to prepare or retain products unstable in the presence of active protons. In addition, the use of nucleophiles which are specifically active toward silicon (e.g., the fluoride anion) enables one to design a process in which the effective concentration of a-nitro carbanions is maintained low. 

T. A Rhodes, K O Shea, G. Bennett, K. P. Johnston, M A Fox, Effect of Solvent-Solute and Solute-Solute Interactions on the Rate of a Michael Addition in Supercritical Fhioroform and Ethane , J. Phys. Chem 1995, 99, 9903-9908. 

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