Aliphatic substrates

The Hammett type of correlation fails with aliphatic substrates just as it does with orf/2o-substituted aromatics. Taft provided the first successful correlations of aliphatic reactions by developing quantitatively an early suggestion of Ingold s that... 

Table 7-9. Polar Substituent Constants, a, for Aliphatic Substrates X-R...

It is also interesting that the yield of monomethyl succinate (R — H), which presumably arises from the abstraction of a hydrogen atom by the aeyloxy radical, is higher in the presence of aromatic than aliphatic substrates. This may mean that the aeyloxy radical is mainly responsible for the abstraction of a hydrogen atom from the initial adduct (26) formed between the alkyl radical and the aromatic substrate (cf. Section II,B). 

The reaction can also be catalyzed by certain thiazolium ylides, in which case it also works with aliphatic substrates. For this modified procedure the following mechanism has been formulated ... 

The opposite case—reaction of an arenediazonium species with an aliphatic substrate —is possible if a sufficiently acidic C—H bond is present e.g. with /3-keto esters and malonic esters. The reaction mechanism is likely to be of the Sel-type an electrophilic substitution at aliphatic carbon ... 

The diazo coupling with C—H acidic aliphatic substrates is a feature of the Japp-Klingemann reaction. 

Stockman has reported the preparation of alkyl-, aryl-, and vinyl-disubstituted aziridines with good diastereoselectivities and in good yields through treatment of tert-butylsulfmylimines with the ylide 119, derived from S-allyl tetrahydrothio-phenium bromide (Scheme 1.39) [64]. A range of substrates were tolerated, including heterocyclic, aromatic, and aliphatic substrates (Table 1.16). 

Atom or radical transfer reactions generally proceed by a SH2 mechanism (substitution, homolytie, bimolecular) that can be depicted as shown in Figure 1.6. This area has been the subject of a number of reviews.1 3 27 97 99 The present discussion is limited, in the main, to hydrogen atom abstraction from aliphatic substrates and the factors which influence rate and specificity of this reaction. 

This mechanism is sometimes called the Se2 mechanism because it is bimolecular, but in this book we reserve that name for aliphatic substrates (see Chapter 12). 

The dehydration of primary amides with hydrosilane catalyzed by iron carbonyl clusters, such as [Et3NH][HFe3(CO)n] and Fe2(CO)9, was achieved by Seller and coworkers in 2009 (Scheme 43) [145]. This reaction shows good functional group tolerance (e.g., such as aromatic, heteroaromatic, and aliphatic substrates). 

Thermally stable nitrilase from Streptomyces sp. MTCC 7546 was induced by benzonitrile enrichment. While discovered by induction with aromatic nitrile, the enzyme was shown to exhibit a strong preference for aliphatic nitriles, with as high as 30-fold greater activity with aliphatic substrates compared with benzonitrile. The enzyme displays optimal activity at pH 7 and 50 °C [56]. 

When cells are grown on non-aliphatic substrates, such as glucose, fructose, acetate, or glycerol, these are converted to appropriate precursors that can be incorporated into poly(3HAMCL)s via fatty acid synthesis. The resulting PHAs have a monomer composition that is similar to that seen after growth on alkanes, often with 3-hydroxydecanoic acid as the major monomer. ( -Oxidation does not seem to play a role in the conversion of these substrates into poly(3HAMCL) since the addition of a -oxidation inhibitor did not affect the monomer composition [47]. 

To perform fed-batch experiments with P. putida a method had to be developed to prevent carbon limitation and to prevent a buildup of the concentration of the fatty acids to inhibitory levels. HPLC methods to measure the concentration of aliphatic substrates and octanoic acid have been reported, but these are not suitable for the detection of long chain fatty acids in a watery phase due to their low solubility. Instead Huijberts et al. [55, 56] developed a method in which discrete pulses of fatty acids were added to fed-batch cultures. Substrate exhaustion was detected by a sudden increase in dissolved oxygen tension and this signal was used to trigger the injection of another fatty acid pulse into the... 

Aliphatic substrates that contain a good leaving group and an a-CH group may undergo reactions by competing nucleophilic substitution and elimination pathways (Scheme l).1 A stepwise mechanism is favored for these reactions... 

The values of ks/kp for partitioning of carbocations are most conveniently determined as the ratio of the yields of products from the competing nucleophile addition and proton transfer reactions (equation 1 derived for Scheme 2). The determination of these product yields has been simplified in recent years by the application of high-pressure liquid chromatography (HPLC). Typically, the product peaks from an HPLC analysis are detected and quantified by UV-vis spectroscopy. In cases where the absorbance of reactants and products is small, substrates may be prepared with a chromophore placed at a sufficient distance so that its effects on the intrinsic reactivity of the carbocationic center are negligible. For example, the aliphatic substrates [1]-Y have proved to be very useful in studies of the reactions of the model tertiary carbocation [1+].21,23... 

SCHUZ, R., HELLER, W., HAHLBROCK, K., Substrate specificity of chalcone synthase from Petroselinum hortense formation of phloroglucinol derivatives from aliphatic substrates, J. Biol. Chern., 1983,258, 6730-6734. 

Eleven aromatic and aliphatic aldehydes have been alkylated with Et2Zn in the presence of homoannularyl bridged hydroxyamino ferrocene (—>123. The resulting carbinols have ee values varying from 66% to 97%. This new ferro-cenyl catalyst has been used successfully to alkylate aromatic and linear or branched chain aliphatic aldehydes to secondary alcohols with up to 97% ee. This ligand is effective even for -branched aliphatic substrate. 

To enhance the efficiency of the cyanide addition, these workers subsequently reported a three-component asymmetric synthesis of amino nitriles that avoids the use of the previously mentioned undesirable stannane [74], Thus, as illustrated in Scheme 6.23, treatment of the requisite aniline and aldehyde with HCN (toxic but cheap and suitable for industrial use) at —45°C in the presence of 2.5 mol% 65 leads to the formation of 67 with 86 % ee and in 80 % yield. As was mentioned above in the context of catalytic asymmetric three-component alkylations of imines (see Scheme 6.18), the in situ procedure is particularly useful for the less stable aliphatic substrates (cf. 71—73, Scheme 6.23). The introduction of the o-Me group on the aniline is reported to lead to higher levels of asymmetric induction, perhaps because with the sterically less demanding aliphatic systems, the imine can exist as a mixture of interconverting cis and trans isomers. 

The CES family of proteins is characterized by the ability to hydrolyze a wide variety of aromatic and aliphatic substrates containing ester, thioester, and amide bonds (Heymann 1980, 1982). Cauxin is a member of the CES family, and is secreted from the proximal straight tubular cells into the urine in a species-, sex-, and age-dependent manner. Therefore, we postulated that cauxin was involved in an enzymatic reaction in cat urine and the products made by the reaction should vary with species, sex, and age. Based on this hypothesis, we searched for physiological substrates and products of cauxin in cat urine and identified 2-amino-7-hydroxy-5,5-dimethyl-4-thiaheptanoic acid, also known as felinine. 

CoH(CN)5] catalyses the hydrogenation of nitro compounds either to amines (aliphatic substrates) or to products of reductive dimerization, i.e. to azo and hydrazo derivatives. Ketoximes and oximes of 2-oxo-adds are hydrogenated to amines. This latter reaction gives a possibihty to directly produce a-amino-acids in the reductive amination of 2-oxo-acids in aqueous ammonia at a temperature of40-50 °C and 70 bar H2 (Scheme 3.1). Yields are usually high (approximately 90%) [18]. 

Similar heteroatom-assisted C—H bond activation also occurs with aliphatic substrates. For example, complex 14 activates the terminal C—H bond of 2-buta-none and affords already at temperatures as low as 60 °C the cyclometaUated complex 16 (Equation 12.8) [27]. 

In concurrent and independent work, Suzuki and Enders found that tethered keto-aldehydes undergo highly enantioselective cross-benzoin reactions using tria-zolium based catalysts [50, 51], The scope includes various aromatic aldehydes with alkyl and aryl ketones (Table 4). Additionally, aliphatic substrate 39a is cyclized in excellent enantioselectivity, albeit in 44% yield. 

Aliphatic substrates also perform well, forming five membered rings in good yield and high enantioselectivity Eq. 6a. Typical Michael acceptors, however, are not sufficiently electrophilic to induce cyclization to form six-membered aliphatic rings. In order to effect this cyclization, use of a more electrophilic Michael acceptor, such as alkylidene malonate 83, was required Eq. 6b [70]. The difference in reactivity is presumably due to the extra conformational freedom of the aliphatic linker compared to the fused aromatic linker of substrate 79 coupled with potential competing non-productive pathways. 

List was the first to explore this possibility, examining the Hantzsch ester mediated reduction of a,P-unsaturated aldehydes [209], Using 20 mol% of the binaphthyl derived phosphonate salt of morpholine (153) in dioxane at 50 °C, a series of P-aryl a,P-unsaturated aldehydes underwent transfer hydrogenation with Hantzsch ester 154 with excellent levels of absolute stereocontrol (96-98% ee) (Scheme 63). The method was also applied to the aliphatic substrates ( )-citral and famesal to give the mono-reduced products in 90% and 92% ee, respectively. Significantly, in line with many of the chiral secondary amine catalysed transformations described above the reactions follow a simple and practical procedure without the need for exclusion of moisture and air. 

The use of soluble amine bases failed to give products, whereas the heterogeneous conditions KOH/THF proved optimal in promoting aldoxime formation for a broad range of substrates. Optically active nitroalkanes including aromatic (both electron-rich and electron-deficient), heteroaromatic, branched and unbranched aliphatic substrates, as well as substrates that incorporate unprotected alcohol functionalities were successfully reduced. 

After successful application in the diethylzinc addition to aromatic aldehydes, we applied our ligands to aliphatic substrates. These substrates still pose a challenge for most types of ligands. 

The application of diastereomeric ligands in the diethylzinc addition to aliphatic substrates demonstrated that two ligands, (Sp,S)-5b and (Rp,S)-5b, always yield appropriate esters 13 with opposite configurations. 

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