Diastereoselectivity, pressure effects, high

A negligible pressure effect on the diastereoselectivity was also observed for the cycloaddition of the enamine carbaldehyde (81a) carrying an electron-withdrawing group at position 3 and 61a to yield the dihydropyrans 82 and 83 (Scheme 8.21). This reaction was again studied by direct quantitative infrared spectroscopy up to 300 MPa between 45 and 95 °C in different solvents. The activation volume was found to be —(25.1 1.7) cm mol in dichloromethane and —(25.0 + 1.8) cm mol in isodurene. Thus, in this reaction solvent polarity had no influence on the pressure dependence of the rate coefficient in addition, the ratio of the two diastereo-meric products is not changed under high pressure thus the AAV value is very small (AAV < 1 cm mol ). 

Intermolecular befera-Diels-Alder reactions of enamino ketones with highly substituted vinyl ethers. Effect of high pressure on the kinetics and diastereoselectivity [77]... 

The Diels-Alder reaction can be greatly enhanced by high pressure (Chapter 5) but the effect of pressure is generally weaker in aqueous medium than in organic solvent. Results of high pressure-mediated Diels-Alder reactions of furans and acrylates in water and dichloromethane are reported in Table 6.6 [32]. In aqueous medium the cycloadditions occur with lower yields and less diastereoselectivity than in dichloromethane and, in some cases, addition-substitution reactions were observed. 

In Scheme 14 the effect of pressure on Diels-Alder reactions with acyclic heterodienophiles or heterodienes is presented. The application of high pressure leads also in these reactions to an enhancement of rates and improvement of yields. The hetero-Diels-Alder reaction (entry 3) is a good example of the interplay between pressure and temperature. At high pressure the rate of reaction as well as the diastereoselectivity are increased. The pressure-induced acceleration allows the temperature of reaction to be lowered, which leads to a further increase of diastereoselectivity. 

An effect of high pressure on the diastereoselectivity is also observed for intramolecular hetero Diels-Alder reactions as found for the cycloaddition of the benzylidene-isoxazolone 8-23 to afford the cis-annulated 8-24 as the major product together with the frans-diastereomer 8-25 (Fig. 8-8) [549], However, the difference in activation volume with AAV =1.6 0.2 cm3 mol"1 is rather small. The activation volume with AV = 19.6 0.5 cm3 mol-1 at 343 K lies significantly below the usual values found for intermolecular cycloadditions of 1-oxa-1,3-butadienes, indicating that this reaction may be on the border line to a two-step reaction but see also below. 

Highly diastereoselective hydrogenation of the chiral allylic alcohols 3 and 4 is obtained with this Rh(I) catalyst at elevated hydrogen pressures (640 psi). At low pressures, the catalyst effects interconversion of 3 and 4. Hydrogenation of 3 and 4 catalyzed by Crab-... 

Geraniol or nerol can be converted to citronellol in 96-99% ee in quantitative yield without saturation of the C(6)-C(7) double bond (eq 6). The S C ratio approaches 50000. The use of alcoholic solvents such as methanol or ethanol and initial H2 pressure greater than 30 atm is required to obtain high enantioselectivity. Diastereoselective hydrogenation of the enantiomerically pure al-lylic alcohol with an azetidinone skeleton proceeds at atmospheric pressure in the presence of an (i )-BINAP-Ru complex to afford the (3-methyl product, a precursor of ip-methylcarbapenem antibiotics (eq 7). Racemic allylic alcohols such as 3-methyl-2-cyclohexenol and 4-hydroxy-2-cyclopentenone can be effectively resolved by the BINAP-Ru-catalyzed hydrogenation (eq 8). ... 

A detailed comparison of normal and high pressure was made in the study of the reaction of cyclopentadiene (1) and the acrylate 2 in the presence of various Lewis acids (Scheme 7.1) f4). In general, the reactions were faster and the yield was increased using pressure, while the effects on selectivity were rather small. The endolexo ratio remained almost unchanged however, it is interesting to note that the diastereoselectivity for the formation of 5 slightly increased using zinc chloride as the catalyst. 

In the discussion of the influence of high pressure on the diastereoselectivity of chemical transformations wc will first look at simple diastereoselectivity and later at induced diastereoselectivity. Most of the work concerning the influence of high pressure on diastereoselectivity has been carried out on Diels-Alder reactions. For an understanding of the effect of pressure on these reactions, a careful analysis of the different pathways must be undertaken. It is usually accepted that in most cases Diels-Alder reactions are concerted, they can, however, also proceed via biradicals or zwitterions depending on the solvents and substrates (Scheme 8.15). 

In contrast, the Michael addition of diphenylmethanamine (155) to the chiral crotonate 154 derived from an arylmenthol-type auxiliary, serves as one of the few examples of a pronounced positive effect of high pressure on induced diastereoselectivity as shown by Dumas et al. [71]. At 1.4 GPa the expected / -amino ester 156, was formed with a high diastereomeric excess of 98 % de, while at atmo-... 

Diels-Alder reactions of 2-pyrones with reactive dienophiles can also be effected without decomposition by use of high pressure (8,254). This version has been used to effect cycloaddition of 3-acyloxy-2-pyrones with vinyl ethers at 25 to give bicyclic adducts in good yield. Use of chiral vinyl ethers can result in diastereoselective reactions. The highest levels of induction are observed with 8-(/3-naphthyl)menthyl vinyl ether and 8-(3,5-dimethylphenyl)menthyl vinyl ether (88 12). 

A remarkable effect on rate enhancement under high pressure is known [40]. The enantiomerically pure isoquinoline 55 was obtained from the bromide 54 in 70% yield and with high diastereoselectivity (16 1) under pressure (10 kbar). The yield was lower than 10% under normal pressure and even under Jeffery s conditions [41],... 

The intramolecular reaction of vinyl-cyclopropanes tethered to alkenes 206 yielding fused bicyclic products 207 has also been applied to the [5-f2-l-l] cycloaddition (Scheme 92) (164). However, in this case, a low partial pressure of CO was found to be effective. Substrates with sulfonamides, ethers, and germinal diesters tethers were effective in the cycloaddition. In addition, substitutions on either the olefin component or the VCP component were also tolerated yielding 5-8 fused ring products with high diastereoselectivity. The ElZ olefin geometry... 

Next, the homochiral crystals were utilized for subsequent diastereoselective reactions. Diastereoselective 2+2 photocydoaddition reaction of amide 20 with methacrylonitrUe was examined. The reaction with methacrylonitrile proceeded effectively, stereo-, and regiospecifically. The amide 20 before crystallization was irradiated in the presence of methacrylonitrile with a high-pressure mercury lamp at 20°C until most of the starting amide was consumed (2 hrs). The photochemical reaction occurred effectively, and 2 + 2 cycloadducts were obtained in 100% chemical yields both diastereomers were endo isomers, minor (lS,2aR,8bR)-23, major (lR,2aS,8bS)-23, and the de value was -25%. Since epamerization was not observed at 20°C, it seems that the de value of the photoproducts should be attributed to the ratio of the diastereomers of the amide 20 before crystallization (-20% de). 

---