Phase-transfer-mediated synthesis

Phase-transfer-mediated synthesis is used for the preparation of NPs. This method involves the transfer of reactants from a polar medium to a non-polar medium, followed by further processing in a non-polar medium. NPs prepared in a non-polar medium can also be phase-transferred to a polar medium. One of earliest reports of... 

LY311727 is an indole acetic acid based selective inhibitor of human non-pancreatic secretory phospholipase A2 (hnpsPLA2) under development by Lilly as a potential treatment for sepsis. The synthesis of LY311727 involved a Nenitzescu indolization reaction as a key step. The Nenitzescu condensation of quinone 4 with the p-aminoacrylate 39 was carried out in CH3NO2 to provide the desired 5-hydroxylindole 40 in 83% yield. Protection of the 5-hydroxyl moiety in indole 40 was accomplished in H2O under phase transfer conditions in 80% yield. Lithium aluminum hydride mediated reduction of the ester functional group in 41 provided the alcohol 42 in 78% yield. 

It is well known that aziridination with allylic ylides is difficult, due to the low reactivity of imines - relative to carbonyl compounds - towards ylide attack, although imines do react with highly reactive sulfur ylides such as Me2S+-CH2-. Dai and coworkers found aziridination with allylic ylides to be possible when the activated imines 22 were treated with allylic sulfonium salts 23 under phase-transfer conditions (Scheme 2.8) [15]. Although the stereoselectivities of the reaction were low, this was the first example of efficient preparation of vinylaziridines by an ylide route. Similar results were obtained with use of arsonium or telluronium salts [16]. The stereoselectivity of aziridination was improved by use of imines activated by a phosphinoyl group [17]. The same group also reported a catalytic sulfonium ylide-mediated aziridination to produce (2-phenylvinyl)aziridines, by treatment of arylsulfonylimines with cinnamyl bromide in the presence of solid K2C03 and catalytic dimethyl sulfide in MeCN [18]. Recently, the synthesis of 3-alkyl-2-vinyl-aziridines by extension of Dai s work was reported [19]. 

Although alcohols are oxidized by tetra-n-butylammonium persulphate when the reaction is conducted in dichloromethane, tetrahydropyranyl ethers have been produced (>90%) when attempts to oxidize the alcohol are conducted in tetrahydro-pyran (see Chapter 10) [ 19], Tetrahydrofuranyl ethers have been prepared by an analogous method [20,21 ]. Base-mediated elimination of halo acids from P-halo alcohols under phase-transfer catalysed conditions produce oxiranes in high yield (70-85%). The reaction has particular use in the synthesis of epihalohydrins from p,y-dihalo alcohols [22],... 

An efficient and highly selective synthesis of bicyclic-a-keto aziridines (89) from 2-bromocyclopent-2-enone (88) and aliphatic primary amines, mediated by phase-transfer catalysts (PTCs) in water at room temperature, has been demonstrated.139... 

Several families of efficient chiral phase transfer catalysts are now available for use in asymmetric synthesis. To date, the highest enantiomeric excesses (>95% ee) are obtained using salts derived from cinchona alkaloids with a 9-anthracenylmethyl substituent on the bridgehead nitrogen (e.g. lb, 2b). These catalysts will be used to improve the enantiose-lectivity of existing asymmetric PTC reactions and will be exploited in other anion-mediated processes both in the laboratory and industrially. 

Early examples of intramolecular aryl radical addition reactions to heteroatom containing multiple bonds included cyclizations on N=N and C=S moieties [52, 53]. Recently, cyclizations to imines have been used as part of a new enantio-selective approach to indolines (Scheme 8). In the first step of the sequence, the required ketimines 19 were obtained by phase-transfer catalyzed alkylation of 2-bromobenzyl bromides 20 with glycinyl imines 21 in the presence of a cincho-nidinium salt [54], Due to the favorable substitution pattern on the imine moiety of 19, the tributyltin hydride mediated radical cyclization to 22 occurred exclusively in the 5-exo mode. The indoline synthesis can therefore also be classified as a radical amination. 

Bromo- and iodoimidazoles are useful intermediates for further functionalization. 4(5)-Aryl- I //-imidazoles 57 can be efficiently and selectively prepared by palladium-catalyzed Suzuki-Miyaura reaction of commercially available 4(5)-bromo-l//-imidazole 56 with arylboronic acids under phase-transfer conditions, which then underwent highly selective palladium-catalyzed and copper(I) iodide mediated direct C-2-arylation with a variety of aryl bromides and iodides under base-free and ligandless conditions to produce 2,4(5)-diaryl-l//-imidazoles 58 in modest to good yields <07JOC8543>. A new procedure for the synthesis of a series of substituted 2-phenylhistamines 60 utilizing a microwave-promoted Suzuki... 

An asymmetric permanganate-promoted oxidative cyclization of 1,5-dienes using a chiral phase-transfer catalyst was recorded <2001AGE4496>, and a diastereoselective permanganate-mediated oxidative cyclization with an Oppolzer sultam has been employed in the total synthesis of m-solamin <20020L3715>. In a metal-oxo-mediated approach to the synthesis of 21,22-di- /)7-membrarollin based on the use of a camphor-derived Oppolzer sultam as... 

The redox-active natural product (+)-methanophenazine (MP) is the first phenazine to be isolated from archea. This compound is able to mediate the electron transport between membrane-bound enzymes and was characterized as the first phenazine derivative involved in the electron transport of biological systems. The research team of U. Beifuss prepared this natural product by using the Williamson ether synthesis in the last step of the synthetic sequence. The etherification was conducted under phase-transfer conditions in a THF/water system in the presence of methyltrioctyl-ammonium chloride and using potassium hydroxide as a base. 

Chou, T. C., J. S. Do, and C. H. Cheng, Using the Mediators/Phase Transfer Catalyst on the Anionic Oxidation of Organic Compounds, Modem Methodology in Organic Synthesis, T. Shono, ed., VCH, New York, p. 283 (1992). 

Jin, Z., Kim, S.H. and Fuchs, PL. (1996) Phosphazene base P2-Et mediated isomerization of vinyl sulfones to allyl sulfones. Tetrahedron Letters, 37, 5247-5248 Jin, Z. and Fuchs, PL. (1996) Use of phosphazene base and phase-transfer conditions for regiospecific alkylative isomerization of vinyl capable of undergoing P-elimination reactions. Tetrahedron Letters, 37, 5249-5252 Kim, S.H., Figueroa, 1. and Fuchs, P.L. (1997) Application of the Grubbs ringclosing metathesis for the construction of a macrocyclic ansa-bridge. Synthesis of the tricyclic core of roseophilin. Tetrahedron Letters, 38, 2601-2604. 

A new synthesis of 5-chloro-l-phenyltetrazole, a useful activating group for the hydrogenolysis of phenols, was reported using NCS-mediated chemistry. The phase-transfer reaction of NCS with sodium azide in chloroform generates chloroazide in situ. The transient chloroazide reacts with phenyl isocyanide via a 1,3-dipolar cycloaddition at 0 °C to afford 5-chloro-l-phenyltetrazole in 69% yield (eq 30). ... 

Supercritical carbon dioxide represents an inexpensive, environmentally benign alternative to conventional solvents for chemical synthesis. In this chapter, we delineate the range of reactions for which supercritical CO2 represents a potentially viable replacement solvent based on solubility considerations and describe the reactors and associated equipment used to explore catalytic and other synthetic reactions in this medium. Three examples of homogeneous catalytic reactions in supercritical CC are presented the copolymerization of CO2 with epoxides, ruthenium>mediated phase transfer oxidation of olefins in a supercritical COa/aqueous system, and the catalyic asymmetric hydrogenation of enamides. The first two classes of reactions proceed in supercritical CO2, but no improvement in reactivity over conventional solvents was observed. Hythogenation reactions, however, exhibit enantioselectivities superior to conventional solvents for several substrates. 

This is an efficient procedure for the synthesis of 2-allq l/aiyl substituted henzo[Z>]furans/nitrohenzo[Z>]furans with water as the solvent. In the presence of PPhs, Cul and prolinol, the corresponding products were formed in good yields (Scheme 2.59). The protocol does not require the use of a phase transfer catalyst or water-soluhle phosphine ligands and is free from the use of any organic co-solvent. As the authors demonstrated, this is the first Pd/C mediated synthesis of henzofuran derivatives, hut the lack of recycling ability was shown in the manuscript. Temperature proved to be critical no product could be observed at room temperature. 

A short synthesis of (-f)-monomorine (1562) by Maruoka and coworkers used the chiral phase-transfer catalyst (R)-1672 to mediate an enantioselective conjugate addition between enone 1673 and the imine-protected glycine ester 1674 (Scheme 213). In a remarkable one-pot reaction, the intermediate adduct 1675 was then treated with Hantzsch ester (diethyl 2,6-dimethyl-l,4-dihydropyridine-3,5-dicarboxylate) in mildly acidic medium, which brought about deprotection of the acetal and imine as well as a double reductive amination in which the dihydropyridine acted as the hydrogen transfer agent. The resulting indolizidine ester (—)-1676 was... 

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