Benzylic ether tether

The use of a functionalized silica-supported salen-nickel complex has allowed Kumada cross-couplings to be performed in flow the corresponding polystyrene supported complex was shown to be inferior for a number of reasons. Catalyst 33 (Figure 4.7) with the longer tether was found to be more active than the benzyl ether tether used for catalyst 34. This was postulated to be due to the fact that catalyst 33 resided further away from the silica surface and hence was more available for reaction. Under the conditions used a maximum conversion of 65% was found for the 1 1 reaction of 4-bromoanisole and phenylmagnesium chloride, which was found to be comparable to that obtained in batch mode. However, during the reaction catalyst degradation was observed and the conversion reduced from 60% in the first hour to 30% in the fifth hour of the reaction [155,156]. 

Scheme 10-16 Triene 44 linked through a benzylic ether tether also undergoes a stereoselective IMDA reaction.

In a related cobalt-catalyzed transformation, 1,3-dienes tethered to ally lie ethers engage in Et2AlCl-mediated reductive cyclization.463 Exposure of benzylic ether 22a to Co(acac)3-PPh3 in the presence of Et2AlCl results in formation of divinylcyclopentane 22b with excellent /raar-diastereoselectivity. As demonstrated by the conversion of 23a to 23b, this method is also applicable to the stereocontrolled formation of six-membered rings (Scheme 16). 

Under Lewis acidic conditions, cyclic acetals such as 72a-b form oxonium ion intermediates which cyclize via an intramolecular Friedel-Crafts alkylation onto the tethered arene to form polycyclic benzylic ethers, Eq. 57 [85]. 

Aqueous sodium hypochlorite is another low-priced oxidant. Very efficient oxidative systems were developed which contain a meso-tetraarylporphyrinato-Mn(III) complex salt as the metal catalyst and a QX as the carrier of hypochlorite from the water phase to the organic environment. These reactions are of interest also as cytochrome P-450 models. Early experiments were concerned with epoxidations of alkenes, oxidations of benzyl alcohol and benzyl ether to benzaldehyde, and chlorination of cyclohexane at room temperature or 0°C. A certain difficulty arose from the fact that the porphyrins were not really stable under the reaction conditions. Several research groups published extensively on optimization, factors governing catalytic efficiency, and stability of the catalysts. Most importantly, axial ligands on the Mn porphyrin (e.g., substituted imidazoles, 4-substituted pyridines and their N-oxides), 2 increases rates and selectivities. This can be demonstrated most impressively with pyridine ligands directly tethered to the porphyrin [72]. Secondly, 2,4- and 2,4,6-trihalo- or 3,5-di-tert-butyl-substituted tetraarylporphyrins are more... 

A final TST example involved insightful conformational control as a design element in the total synthesis of spirofungin A by Marjanovic and Kozmin. The key spiroketalization involved deprotection of the benzyl protecting groups of 38 with concomitant hydrogenation of the two olefins to provide a keto-diol confor-mationally constrained by the bissilyl ether tether. In situ cycliza-tion delivered the desired 1,3-diaxially encumbered spiroketal 39 as a single diastereomer in near-quantitative yield (eq 11). ... 

Intermolecular reactions between 0-benzyl oximes and ketones (or aldehydes) are limited to those with formaldehyde O-benzyl oxime. However, intramolecular coupling proceeds with carbonyl-tethered oxime ethers (Equation (69)). 

In a third variant on this theme, methyl 3,4,6-tri-O-benzyl-l-thio-a-D-mannopyranoside is converted into a p-methoxybenzyl acetal by first etherifying the 2-OH group with p-methoxyben/yl bromide and then treating the resulting p-methoxybenzyl ether with a hydroxyl compound in the presence of 2,3 -dichloro-5,6-dicyano-l,4-benzoquinone (DDQ). Activation of the methylthio anomeric center with methyl triflate then produces the (3-D-mannopyranoside as the only possible glycoside, again because of the acceptor being tethered to the (3 side of the mannopyranoside.56... 

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