Control of regioselectivity:oxidation and deprotection
Palladium is a highly versatile metal, capable of catalysing oxidations, reductions and a myriad of organic transformations. The inorganic chemistry of palladium, and the relation of this to the catalytic activity of the metal, is briefly discussed. A short survey of the range of palladiumcatalysed reactions is undertaken. The Wacker reaction, the palladium(II)-catalysed oxidation of alkenes to carbonyls, is considered in detail. In the absence of heteroatoms, the Wacker reaction of terminal alkenes is known to produce methyl ketones. However, it is shown that the Wacker reaction of styrenes is unusual; under reoxidant-free conditions, the reaction proceeds to give aldehydes as the major products. The scope of this transformation is probed with a series of ring-substituted styrenes: it is found to be general for all substituents studied. The mechanism responsible for this anti-Markovnikov regioselectivity is investigated. Palladium(0) is eliminated as a possible cause of unusual reactivity. NMR studies and reactions of suitable substrates are used to suggest a side-on complex of either an agostic or 4-type. Kinetic studies show no evidence of an agostic interaction, and thus an 4-complex is more likely. Attempts at achieving catalytic activity in the formation of aldehydes are unsuccessful with small-molecule reoxidants. However, the use of heteropolyacids is found to lead to a catalytic reaction. A second source of unexpected regioselectivity in the Wacker reaction is the agostic interaction of hydrogens on the allylic position with the palladium centre. Some new evidence is obtained for this effect in the reaction of 1-phenylbut-1-ene and 1-phenyl-3-methylbut-1-ene. Attempts are made to gain additional insight by seeking a kinetic isotope effect in the Wacker reaction of dec-1-ene and a partially-deuterated analogue. Some evidence of a kinetic isotope effect is found. The use of benzyl (Bn) groups is one of the most common methods used in synthesis to protect alcohols and amines. The method of choice for the removal of Bn groups is hydrogenolysis over a palladium catalyst. Oxidative deprotection methods are also available, particularly when the MPM (4-methoxybenzyl) group is used in place of Bn. The NAP (2-naphthylmethyl) protective group has recently been introduced and has been shown to be removed by hydrogenolysis more readily than Bn groups. The usefulness of the NAP group is extended: it is demonstrated that NAP is less sensitive to oxidative cleavage with CAN [hexa-amminecerium(IV) nitrate(V)] than MPM. A series of glucose-based substrates are prepared, and used to demonstrate this oxidative selectivity.
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