Carbonyl compounds phase-transfer catalysis

Preparation of a-DiAzo Carbonyl Compounds via Phase Transfer Catalysis ... 

Phase transfer catalysis, or more correctly, two-phase systems, were widely applied in the synthesis of oxiranes via generation of sulfonium and sulfoxo-nium ylides and their subsequent reactions with carbonyl compounds.67... 

The first experiments which were carried out in the author s laboratory on organometallic phase-transfer catalysis were concerned with the reduction of nitrobenzenes (4) to anilines (5) by triiron dodecacarbonyl. Such a conversion was reported to occur in benzene containing methanol at reflux for 10-17 h, with the hydridoundecacarbonyltriferrate anion as the likely key intermediate (16). It was our expectation that the trinuclear iron hydride should be generated by phase-transfer catalysis and if so, effect reduction of nitro compounds (4) under exceedingly mild conditions. Indeed this was the case, as illustrated by the results shown in Table I (17). Not only is the reaction complete in 2 h or less using sodium hydroxide as the aqueous phase, benzene as the organic phase, and benzyltrieth-ylammonium chloride as the phase-transfer catalyst, but it occurs at room temperature and requires less metal carbonyl than when the reaction was... 

Another important asymmetric epoxidation of a conjugated systems is the reaction of alkenes with polyleucine, DBU and urea H2O2, giving an epoxy-carbonyl compound with good enantioselectivity. The hydroperoxide anion epoxidation of conjugated carbonyl compounds with a polyamino acid, such as poly-L-alanine or poly-L-leucine is known as the Julia—Colonna epoxidation Epoxidation of conjugated ketones to give nonracemic epoxy-ketones was done with aq. NaOCl and a Cinchona alkaloid derivative as catalyst. A triphasic phase-transfer catalysis protocol has also been developed. p-Peptides have been used as catalysts in this reaction. ... 

Acid-catalyzed addition of aliphatic, aromatic or heteroaromatic cyanohydrins to ethyl vinyl ether, n-butyl vinyl ether or dihydro-4//-pyran provides base stable, protected cyanohydrin derivatives. Phase transfer catalyzed alkylation of aliphatic cyanohydrins with allylic bromides gave a-substituted a-allyl-oxyacetonitrile. Carbonyl compounds react wiA cyanide under phase transfer catalysis to give cyanohydrin anions, which are trapped by an acyl chloride or ethyl chloroformate to give acyl- or alkoxycarbonyl-protected cyanohydrins respectively. The reduction of the carbonyl group of an acyl cyanide by NaBH4 under phase transfer conditions followed by esterification serves as an alternative route to aldehyde-derived cyanohydrin esters. ... 

In conclusion, the 1,3-dithiane unit still remains among the most valuable acyl anion equivalents, although that involving methyl methylthio sulfoxide or its diethyl analog offers the definite advantages of proceeding with metal hydride or even under phase-transfer catalysis conditions and of producing the carbonyl compound under reasonably mild conditions. 

The Darzens reaction (tandem aldol-intramolecular cyclization sequence reaction) is a powerful complementary approach to epoxidation (see Chapter 5) that can be used for the synthesis of a,P-epoxy carbonyl and a,p-epoxysulfonyl compounds (Scheme 8.32). Currently, all catalytic asymmetric variants of the Darzens reactions are based on chiral phase-transfer catalysis using quaternary ammonium salts as catalysts. 

Recently, two methods were published that have attracted some interest, because no metal salts are necessary as oxidation reagents. Shi and Xu (1990) found that substituted (trifluoromethyl)-diazoalkanes (CF3CRN2, R = alkyl or aryl) are obtained by refluxing trifluoromethyl ketones and 2,4,6-tri(isopropyl)benzenesulfonyl hydrazone in a methanolic solution of KOH. Kumar (1991) synthesized a-diazocar-bonyl compounds under tri-phase phase-transfer catalysis using a polystyrene-supported (tributyl)(methyl)-ammonium chloride catalyst, methanesulfonyl chloride, NaN3, and methylsulfonyl azide in 1,2-dichloroethane and a carbonyl-activated substrate (69-94% yield). 

The steroidal a-(isocyanomethyl)phosphonates (130) and (133) have been synthesized by methylation of the carbanions (129) and (132), respectively.66 Compounds (130) and (133) behave as N,P-ketals in that they can be hydrolysed to the corresponding ketones (131) and (134) (Scheme 10). A range of a-substituted a-aminophosphonic acids (136) have been prepared in moderate to excellent yield by the alkylation of the protected a-aminophosphonate (135) with alkyl and aryl halides and Michael acceptors under phase transfer catalysis (Scheme 11).67 The reactions of the lithium carbanion of diethyl prop-2-enyIphosphonate (137) with a,P-unsaturated ketones and esters have been investigated.6S Attack can be at the a- or y-positions in the phosphonate although in all cases Michael addition to the a, p-unsaturated carbonyl is preferred to attack at carbonyl carbon. In some examples simple adducts (138) are formed, but in more complex cases addition is followed by cyclisation to give (139) (Scheme 12). The bisphosphonate (141), which is a potent inhibitor of myo-inositol monophosphatase, has been prepared with the phosphonylation of the carbanion of (140) as a key step.6 9... 

The temperature required for the formation of diazoalkanes can be significantly decreased by using phase-transfer catalysis. This method has allowed the use of transition metals in the catalytic asymmetric epoxidation of carbonyl compounds (eq 19). The use of phase-transfer catalysis and moderate temperatures promotes the formation of diazoalkanes at a very low rate, achieving low concentrations of diazoalkane during the reaction, which is critical for the outcome of the process. The use of trisylhydrazone has shown better results in some cases compared to its tosyl analog. Presumably, the bulkier sulfonyl group may facilitate the... 

Phase transfer catalysis, which proved extremely useful in classical ylid reactions with both phosphonium and sulfonium salts (Ref, 8, 42-45), was first used with a polymer by Farrall, Durst and Frechet in 1978 (Ref, 15) according to scheme 4. In this reaction, the polymeric sulfonium salt (IX), which is suspended in a dichloromethane solution of the carbonyl compound, is treated with aqueous sodium hydroxide in the presence of tetrabutyl ammonium hydroxide to give over 95% yield of the desired epoxide together with a polymeric by-product (X) which can be recycled and reused repeatedly without any loss of activity. In contrast, the same polymeric reagent (IX) used under classical conditions affords lower yields of epoxides and loses its activity rapidly on repeated recycling. This last observation shows clearly that phase transfer catalysis may contribute significantly to the prevention of side reactions in some modifications of polymers. 

The versatile nature of cinchona alkaloid ammonium salts for phase-transfer catalysis can be illustrated by recent reports on conjugate additions [118] and a nitro-Mannich reachon [119]. Dimeric catalysts derived from quinine and quini-dine were applied in the conjugate addition of cyclic (l-ketoesters to a, 3-unsaturated carbonyl compounds. The reaction proceeded in the presence of a tertiary amine as base and afforded the products in moderate to high yield and enantioselectivity (Scheme 6.56). 

In certain cases, the reduction can take place without electrophilic catalysis (n-BU4NBH4 or phase-transfer conditions), but most frequently it requires the coordination of the carbonyl group by a Lewis acid before nucleophilic attack [S2]. The Lewis acid may be the cation associated with the reagent, an added acid, or even the boron or aluminum atom of tricoordinate reagents (AIH3, DIBAH, boranes). The importance of this phenomenon has been shown by the introduction of coordinating macrocyclic molecules into solutions of LAH and LiBH4. This considerably retards the reduction of carbonyl compounds in an ether medium [DCl, HPl], Electrophilic catalysis is more important when the lowest unoccupied molecular orbital (LUMO)... 

In contrast to covalent bond catalysts that form covalent substrate-catalyst adducts, hydrogen bond catalysts activate carbonyl compounds via weak interactions such as hydrogen bonding. Bronsted acid catalysts form ion pairs by protonating imines. The concept of counteranion catalysis has also been proposed. Phase-transfer catalysts also form ion pairs. 

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