Regioselective processes

This review article offers an overview of stereo- and regioselective processes, developed in our laboratories, that are carried out in conjunction with various catalytic RCM reactions. As mentioned above, several reaction technologies involve stereoselective functionalization of the RCM products, and others were developed such that subsequent reactions effected by a metathesis catalyst promote the formation of the desired target molecules selectively and efficiently. 

Butanal by hydroformylation of propene is the most important oxo product in terms of volume. Six million metric tons per year of butanals were consumed in 2003, vis-a-vis a capacity of 7.6 million metric tons. Highly chemo- and regioselective processes based on ligand-modified rhodium catalysts have been developed and replaced the original cobalt high pressure technology. 

Particularly in [32] it was shown that cycloaddition of the chalcones 10 and diazomethane is a regioselective process providing 3-aroyl-4-aryl-2-pyrazolines 12, most likely via heterocycles 11. These are the sole products irrespective of the bulkiness and/or the electronic influence of the two aryl moieties of the starting a,(3-unsaturated ketones 10 (Scheme 2.4). 

Decomposition of 1-aryl-3,3-dialkyltriazenes in the presence of Mel is a regioselective process to generate an aryl iodide (equation 175)1098 ... 

Several 2-substituted 3,4-diarylpyrroles 3 have been prepared in a regioselective process employing the base induced addition of methyl isocyanoacetate to the a,f -unsaturated nitriles 4, and one of the pyrroles so obtained was used in a concise synthesis of the alkaloid ningalin B... 

Vinyl silanes react with electrophiles in a highly regioselective process in which the silicon is replaced by the electrophile at the ipso carbon atom. The stereochemistry of the vinyl silane is important because this exchange usually occurs with retention of geometry as well. Consider the reaction of the two vinyl silanes derived from phenyl acetylene with the simple electrophile D+. Deuterons are chemically very similar to protons but are, of course, distinguishable by NMR. 

In some cases vinyl esters have been successfirlly used for these regioselective processes (Scheme 10.6). Thus, CALB catalyzes the selective monobenzoylation at the 5 -hydroxyl group of 2 -deoxynucleosides using vinyl benzoate as the acyl... 

The single most important reaction of cyclopropenium ions involves their capture by nucleophiles Such reactions give the corresponding cyclopropene which may survive the reaction conditions i4c,27o, 536 eliminate to yield a triafulvene (Section II.G), ionize to a new cyclopropenium ion " " , or ring cleave With unsymmetrically substituted cyclopropenium ions mixtures of cyclopropenes are often produced (equation 110) although regioselective processes are known . 

The regioselective process P-amino-a-hydroxycarboxylic acid corresponding acrylic acid substn anthraquinone mediates enantiosele... 

The regioselective process is suitable for the synthesis of protected (3-amino-a-hydroxycarboxylic acid derivatives (racemic, no chiral ligand added) from the corresponding acrylic acid substrates. On the other hand, 1,4-bis(dihydroquininoxy)-anthraquinone mediates enantioselective formation of A-benzyloxycarbonylphenylserine. ... 

The Hosomi-Sakurai reaction is a powerful method for conjugate allylation of a,fi-unsaturated ketones [425], In the presence of TiCl4 the allylation occurs smoothly at the y-position of allylsilanes and the / -position of a, -unsaturated ketones. This highly regioselective process has been widely used for introduction of functionalized carbon chains and construction of carbocycles in natural product synthesis [6, 426]. When TBAF is used as catalyst, both conjugate addition and 1,2-addition occur competitively [333]. The fluoride ion-catalyzed procedure is, however, effec-... 

As with hydroformylation, a mixture of isomeric acids is usually formed. Much effort has been directed toward obtaining regioselective processes for both the linear and the branched products. 

This relatively mild and highly regioselective process allowed C-H alkenylation with both electron deficient acrylates and more unactivated alkenes. Switchable regioselectivity was achieved by varying the reaction media and chemical oxidant. 

Anodic monofluorination of 5-methyl- and 6-methyl-4-oxo-2-pyrimidyl sulfides using Et4NF-4HF is a highly regioselective process (Table 16) (91T3969). DME is... 

Much effort has been devoted to developing catalysts that control the enantioselectiv-ity of these substitution reactions, as well as the regioselectivity of reactions that proceed through unsymmetrical allylic intermediates. A majority of this effort has been spent on developing palladium complexes as catalysts. Increasingly, however, complexes of molybdenum, tungsten, ruthenium, rhodium, and iridium have been studied as catalysts for enantioselective and regioselective processes. In parallel with these studies of allylic substitution catalyzed by complexes of transition metals, studies on allylic substitution catalyzed by complexes of copper have been conducted. These reactions often occur to form products of Sj 2 substitution. As catalylic allylic substitution has been developed, this process has been applied in many different ways to the synthesis of natural products. ... 

In a transition metal-free, one-pot, and regioselective process, 2-halo-benzenethiols 195 or 3-chloro-5-(trifluoromethyl)pyridine-2-thiol 196 reacted with N-substituted nitrobenzamides 197 to afford a library of dibenzo[I>,/][l,4]thiazepin-ll(10id)-ones 198 or pyridobenzothiazepines 199, respectively, via a Smiles rearrangement (13ACO130). 

In most cases, halohydrin formation is observed to be a regioselective process. Specifically, the OH is generally positioned at the more substituted position ... 

In 2010, Janssen and co-workers reported that the kinetic resolution of p-phenylalanine catalysed by a tandem biocatalytic system composed of phenylalanine aminomutase (PAM) and phenylalanine ammonia lyase (PAL) yielded the corresponding enantiopure (5)-p-phenylalanine in good yield (48%) and excellent enantiomeric excess of >99% ee (Scheme 4.13). The process was based upon the PAM-catalysed, reversible, enantioselective transformation of (I )-p-phenylalanine to (S)-a-phenylalanine. The latter one was transformed in a PAL-catalysed regioselective process into ( )-cinnamic acid, with liberation of ammonia. This constituted an example of a tandem biocatalytic, kinetic resolution in which one enzyme catalysed the equilibration between the substrate and reaction intermediate, while the other shifted this equilibrium between the substrate towards the final product... 

The aUyl benzyl ether 162 is substituted with two quite different nucleophiles in retentive, regioselective processes with complete chirality transfer [75, 76). 

This was indeed shown to be the case, and as expected this in situ capture of the rearrangement product 108 proved to be a stereoselective and regioselective process [36]. 

Related and regioselective processes have been exploited in the preparation of novel lactone-annulated steroids (eq 98). ... 

---