Time scheme

The allylation reaction of the optically active tetronic acid derivatives 146 was shown to give a variety of isomers depending on the reaction conditions (temperature and reaction time) (Scheme 44 and Table I) (99H1321). The reaction is carried out by treating 146 with allyl bromide in DMF and in the presence of K2CO3. 

Diels-Alder reactions of vinylpyrazoles 45 and 46 only occur with highly reactive dienophiles under severe conditions (8-10 atm, 120-140 °C, several days). MW irradiation in solvent-free conditions also has a beneficial effect [40b] on the reaction time (Scheme 4.11). The indazole 48, present in large amounts in the cycloaddition of 45 with dimethylacetylenedicarboxylate, is the result of an ene reaction of primary Diels-Alder adduct with a second molecule of dienophile followed by two [l,3]-sigmatropic hydrogen shifts [42]. The MW-assisted cycloaddition of 46 with the poorly reactive dienophile ethylphenyl-propiolate (Scheme 4.11) is significant under the classical thermal reaction conditions (140 °C, 6d) only polymerization or decomposition products were detected. 

Oxidative Heck arylation of enamides with arylboronic acids, using oxygen gas as a reoxidant for Pd(0) and 2,9-dimethyl-1,10-phenanthroline as a chelating regiocontrolling ligand, yielded a (= internally) arylated reaction product as the major compound with a very good a//3 selectivity [92]. Microwave irradiation with prepressurized sealed vials proved useful in reducing the reaction time (Scheme 82). 

The barium phosphonium dibenzylide 18, first organobarium compound not belonging to the cyclopentadienyl series, was isolated at the same time (Scheme 12) [58]. In the latter, the Ba + ion is encapsulated by two C2-symmet-ric phosphonium ligands of opposite chirality. 

Hydro carbonylation of olefins, hydroformylation, hydroesterification and hy-droxycarbonylation are reactions which appear to be of particular interest. Indeed, they allow the simultaneous creation of a new C - C bond as well as the introduction of a functional group (aldehyde, ester and acids). One or two new stereogenic centres can thus be formed at the same time (Scheme 26). Despite the difficulty of using high carbon monoxide pressure, the aheady existing industrial processes prove that such reactions can be performed on a very large scale [107]. 

The reaction in the presence of h/s-ethylene complex 38 proceeds in 6 h, while complexes 39 and 40 need a somewhat longer reaction time (Scheme 9). This may be explained by the more facile and irreversible substitution of the volatile ethylene... 

Similar reactions have been developed more recently by Jin et al. using chiral amino thioacetate ligands derived from the corresponding amino alcohols. Low catalyst loadings of only 1-2.5 mol% were sufficient to achieve excellent enantioselectivities of up to 98% ee as well as high conversions in short times (Scheme 3.61). These authors have shown that the thioacetoxy moiety of the amino thioacetates has a surprisingly beneficial effect in enhancing the asymmetric induction. 

Surprisingly, in contrast to the reaction of the Si=P bond with mesityl azide, the reaction of 15a with diphenyldiazomethane resulted in the formation of the [2+l]-cycloadduct 35 (Scheme S).38 The bonding situation in 35 (Fig. 11) may be described in terms of a 7r-complex, by employing the Dewar-Chatt-Duncanson model, in which the Si=P bond acts as v donor and acceptor at the same time (Scheme 9). The corresponding [2+31-cycloaddition product 36 was generated only on thermal activation of 35. 

The highly reactive DTT 15a undergoes double electrophilic substitution with 1,2-ethanedisulfenyl chloride in the presence of AICI3 or FeCl3 in dichloromethane to give compound 114, a very interesting donor that combines the DTT 15a aromatic core with extensive sulfur substituents for the first time (Scheme 6) <2001SM(120)1061>. 

The corresponding bridgehead heterocydes are difficult to obtain by conventional heating methods since the reactions of a-tosyloxyketones with ethylenethioureas remain incomplete in an oil bath. The microwave-accelerated process, on the other hand, gets completed in a short time (Scheme 6.44) [147,148],... 

Aziridines, the smallest heterocycles, are an important class of compounds in organic chemistry. Interesting access [8] to aziridines by using Bromamine-T as a source of nitrogen in the copper (Il)-catalyzed aziridination of olefins in MeCN was recently reported. Application of microwaves has resulted in enhanced yields for aziridines [9] with short reaction times (Scheme 8.5). 

A comparative study [12] of the reactivity of the oxalimide 16 in a variety of solvents (xylene, chlorobenzene, toluene) and of methylphosphinite 17 was performed with the focused microwave Synthewave 402 reactor (Merck Eurolab, div. Prolabo, France), using different conditions of power and exposure time (Scheme 8.8). In all experiments yields were better than those of previous procedures with classical heating (Tab. 8.2), and the authors wrote it is dear that microwave technique is applicable to highly functionalized compounds containing stereogenic centers without appreciable modification of these centers . 

Bortolussi described the synthesis of unsaturated amino alcohols 83 by thermolysis of furan adducts 82 use of microwaves resulted in a significant reduction in reaction time (Scheme 9.24) [75],... 

When a phenylsulphonyl EWG is used, the product depends on the reaction time (Scheme 12). Shorter times lead to mixtures of A and B. 

FIGURE 2.2 Timing scheme for dual-stream HPLC with guard column regeneration. 

Instrumentation — The parallel LC/MS/MS system for this application was operated under the dual online SPE mode. Figure 2.7 is a flow diagram for the dual stream and Figure 2.8 depicts the staggered timing scheme. Figure 2.9 shows the autosampler setup in action. 

The AlCl3-mediated acylation of but-l-en-3-ynes such as 106 to give mixtures of allenyl ketones of type 107 and 1,2-addition products such as 108 have been published several times (Scheme 7.16) [144, 145]. In the case of other substitution patterns of the starting enynes, the stereochemistry of the resulting allenyl ketones was investigated [146]. 

Boger and Zhang s assembly of the intramolecular Diels-Alder adduct 97 is carried out by reacting 1,2-diazine 95 and allene 96 at high pressure for an extended time (Scheme 19.18) [22]. On heating to 120 °C, an intramolecular Diels-Alder reac-... 

Four-centered addition of RCu to an enone was widely discussed in the 1960s (Scheme 10.3a) [51-53], while discussions on six-centered transition states have continued until recent times (Scheme 10.3b) [54]. These mechanisms do not, however, explain the formation of E/Z mixtures of enolate stereoisomers [20, 55] and must now be considered obsolete. 

Fig. 21. Timing scheme of a STEAM sequence for diffusion measurements with a pair of diffusion weighting dephasing/rephasing gradients. Parameters 8, A, and A determine the diffusion weighting (h-value).

In addition, the intermediates from various stages of the reaction sequence can be incorporated into alternative reaction pathways allowing access to large number of heterocychc compounds in a relatively short period of time (Scheme 2.62). Clearly, being able to change the core stracture is as crucially important as changing the fin-... 

The first publications to describe the phosphane oxide-catalyzed carbodi-imide synthesis from isocyanate appeared in 1962. In this case iminophos-phoranes were recognized as important intermediates. The first mechanistic studies also appeared at this time. Scheme 24 depicts the proposed two-step mechanism (62JA3673, 62JA4288 66CJC2793). 

The Alder-ene reaction of these substrates occurs with little or no interference from the additional unsaturated functionality appended to the tether, based on the excellent yields and fast reaction times (Scheme 8.6). 

A significant improvement in the conduction of this reaction was reported under microflow conditions in comparison with batch mode. Batch conditions involved a reaction time of 60 h at room temperature to afford the final product in a 62% yield. Under optimized microreactor conditions, the online HPLC-determined yield was 91 % in a 60 min reaction time (Scheme 2). Note that the microreactor setup allowed the reaction temperature to be higher than the atmospheric boiling point of the solvent. 

Reagents were injected in pairs. After a series of trials with different flows, concentrations, solvents and temperatures, the reaction was optimized at 120°C and a 118 min residence time (Scheme 5). 

Allylic arylations of substituted cinnamyl acetates can be carried out with Ar3Bi under Pd catalysis. The couplings afforded 1,3-diarylpropenes in good yields in short reaction times (Scheme 52) [66],... 

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