Reactions at the Side-Chain

Boron trifluoride catalyses the 1,3-phosphotropic rearrangement of the a-phosphorylated imine (65) to give (66).35 This reaction takes place at room temperature, whereas the uncatalysed reaction requires heating to 150-2000C. High yields of the addition products (67) have been obtained from the reaction of carbon-centred radicals with diphenylvinylphosphine oxide.36 Radical addition to the chiral phosphine oxides (68) using Barton s method provides diastereomeric ratios of up to 9 1 in the case of (69). 

Interestingly, while 2-hydroxyalkylphosphines undergo Rabbit gastric lipase-catalysed acylation, the corresponding phosphine oxides and sulphides either react more slowly or not at all.39 

an interactive computer program for the mechanistic evaluation of organic reactions, has been extended to include the reactions of phosphine oxide-stabilised carbanions.27 A convenient route to 3-methoxy-l-trimethylsilyl-1,3-dienes (50) is available from a one-pot 

Phosphine oxide-based olefination has been used to synthesise a variety of natural products. The pheromones (52) and (53) of the 

In view of the usefulness of alkoxyphosphonium salts in synthesis it is of interest to note that, depending on the mode of addition of the 

An addition-elimination reaction of 1-halogenovinyldiphenyl-phosphine oxides (76) has been used to prepare a wide variety of trans- 

2-diphosphinyl-(77), 1-sulphinyl-2-phosphinyl-(78), 1-sulphoxyl-2-phosphinyl- and l-sulphonyl-2-phosphinyl ethenes.36 Similar reactions of the optically active 1-halogenovinylmethylphenylphosphine oxide (79) provide routes to optically active 1,2-diphosphinyl ethenes (80) and (81) and l-sulphinyl-2-phosphinyl ethene (82). 

Warren continues to extend his phosphine oxide-based method of stereoselective olefin synthesis. The previously published method of acyl transfer followed by borohydride reduction to give selectively the threo-hydroxyalkylphosphine oxide intermediate has now been applied to more complex examples carrying other chiral centres.28 Optically active butyl(2-methoxyphenyOphosphine oxide (47) has been used to provide a chiral 

Two reports of syntheses of the complex phosphine oxide (59) and its use in the synthesis of the C10-C34 fragment of FK506, a highly potent immunosuppressant macrolactam, have appeared.33,34 

Aliphatic and aromatic thiols have been added to (5) -methylphenylvinylphosphine oxide (84) to provide optically active P-alkylthio- and p-arylthioethylphenylphosphine oxides (85).The reaction of the phosphine sulphide (86) with tetrachloro-o-benzoquinone gives (87) which undergoes further rearrangement.  

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Also, ferric ion promotes nuclear (ionic) bromination of benzene derivatives at the expense of the radical reaction at the side chain. 

Continuous reactions at the side chains of branched or comblike structured polymers play an important role in the solid-phase synthesis of peptides or oli-go-nucleotides. 

The major application of 1,3-heterocycles discussed herein is their function as protecting groups. It is obvious that numerous reactions at the side chain have been carried out in the presence of the heterocycles. The focus in this section is (1) transformations close to the heterocycle, one to two atoms away (2) interesting (though this is somewhat subjective) reaction at longer distances and (3) transformations in the side chain influenced by the heterocycle. 

The report made in connection with a reaction between 1-dimethylaminoisoquinoline and Mel at 20° invites speculation. Quater-nization of the annular nitrogen atom results.94 This contrasts with reaction at the side chain of both 2-dimethylaminopyridine97 102 and 2-dimethylaminoquinoline94 under similar conditions. Perhaps the neighboring peri-hydrogen causes the dimethylamino group to adopt a conformation that minimizes its steric effect and thereby allows the isoquinoline to react at the annular position. 

Epichlorohydrin elastomers may be chemically modified by nucleophilic substitution reactions at the side-chain chloromethyl group. Numerous substituted products have found applications as flame retardants, flocculating agents, selectively permeable membranes, photosensi ti ve materials, etc. 

Butyllithium reacts with 1,2-dimethylimidazole at -80 °C to lithiate the 2-methyl group, and at higher temperatures some 5-metalation also occurs (74JOC2301). Reaction of 2-methyl-, 5-chloro-2-methyl- and 2-benzyl-benzimidazoles with two molar equivalents of butyllithium in THF-hexane at 0 C results in dilithiation, although subsequent reactions at the side-chain carbanion centre also take place (Scheme 96) (73JOC4379). 

The pyrolysis products of acrylic acid indicate that only about 25% of monomer is generated during pyrolysis. A significant amount of decarboxylation takes place during pyrolysis. Also, water is present in the pyrolysate (about 15%). The elimination of CO2 may take place as a simple reaction at the side chain of the polymer as shown below ... 

Ethyl-6-methyl- and 2,6-dimethyl-3-pyridinol react with piperidine, di-methylamine, and morpholine in aqueous formaldehyde to form 4-dialkylamino-methylated products that have been used to prepare vitamin Be analogs XII-681 and XU-682. Reaction at the side-chain is not observed. 

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