Oxocarbenium intermediate

Treatment of the halides 16 with an alcohol promoted by silver salts does yield mainly the p-glycosides 17 (28. 29[,). Obviously the bromo substituent directs the incoming nucleophile by steric reasons or possibly via a 1,2-bromonium<->bromo-oxocarbenium intermediate. Following a reduction step, the syntheses of p-glycosides 18... 

The hexacycle was likely a result of intramolecular trapping of the incipient oxocarbenium intermediate by the Cl-OH. 

Finally, Rychnovsky and Cossrow [33] preferred to use optically pure a-trimethyl-silylbenzylether 64 as the chiral auxiliary. In this case, the oxocarbenium intermediate 64b adopts a well-defined conformation, proposed initially by Linderman [34], which provides the maximum /hsilyl-effect. The nucleophile then approaches from the opposite side of the TMS group (Scheme 13.27). 

The conversion of enol ether 80 to cyclic ketal 83 in water in 12% yield exemplifies the chemoselectivity possible with 14D9.79 Although 83 is the normal product of the acid-catalyzed hydrolysis of 80 in organic solvents, it is never observed in water because the highly reactive oxocarbenium intermediate is rapidly trapped by the solvent to give ketone 82 (via hemiacetal 81) as the sole product. The ability of the antibody to protect the reactive oxonium ion intermediate from hydrolysis and partition it toward a product that is not typically observed under these conditions (i.e., 83) mimics the capabilities of rather sophisticated enzymes. Extension to other reactions involving reactive, water-incompatible intermediates can be easily imagined. 

SCHEME 16.1 Acidic glucoside hydrolysis via oxocarbenium intermediate 6. 

It is controversial whether DNJ 9 can be regarded as a true transition-state analog. Although protonated DNJ does mimic the charge development of the oxocarbenium intermediate 6 (Scheme 16.1), it adopts a chair conformation instead of the expected halfchair conformation of 6. A linear free-energy relationship analysis vs. which tested... 

Brevetoxin B and related marine natural products present remarkable molecular architectures of transfused poly ether skeletons. Kadota and Yamamoto have reviewed a substantial body of results for linear and convergent approaches for the synthesis of these substances based on intra-molecular allylations.4° An attractive convergent concept illustrates the intra-molecular allylation of the oxocarbenium intermediate generated from a-acetoxyether 154 leading to stereocontrolled production of the divinyl ether 155. Ringclosing metathesis of 155 directly yields polycyclic ether 156 (Scheme 5.2.32). ... 

Recourse has therefore been taken to adopt the strategy successfully used for (3-mannosides, employing intramolecular aglycon delivery, namely, using a tether that forces the nucleophile to approach the oxocarbenium intermediate from the (3... 

As nucleophihc ring-opening of epoxides is analogous to nucleophihc substitutions, the latter will not be described in this section. In addition, the hemiketalization/nucleophilic addition sequence involving the creation of a C—C bond through a nucleophihc addition onto an oxocarbenium intermediate wiU be described in the Section 3. 

The addition of a nucleophile on an oxocarbenium intermediate is also an efficient way to access 2,6 ds-THPs and 2,6 tra 5-THPs depending on the substitution pattern of the hemiketal/ketal and on the conditions. An axial attack of the nucleophile on the six-membered half-chair G occurred from the side that favors the low-energy chair transition state rather than the twist-boat transition state (Scheme 35). 

Nucleophiles other than hydrides can be used, such as aUylsilanes, siloxy-dienes, or silyl enol ethers, to access substituted THPs from cyclic ketals. Rych-novsky et al. and Wipf et al. synthesized one THP of leucascandrolide A from ketal 76 by using a nucleophilic addition of aUylsilane in the presence of BF3 Et20. The diastereoselectivity of the reaction was explained by an axial attack on the half-chair oxocarbenium intermediate. The double bond was then transformed into the corresponding aldehyde by ozonolysis to afibrd further functionalizations (Scheme 38) (2001JA8420 2002CC2066). 

In a tandem isomerization/Prins strategy utilizing cooperative catalysis between an iridium(III) catalyst and a Bronsted acid, indole 182 underwent an isomerization/protonation sequence via a Prins-type oxocarbenium intermediate, with subsequent C—C bond formation to give oxepane-fused indole 183 (13AGE12910). Various anthranilic acids were coupled with chiral a-haloacids to afford N-acylated anthranilic acid intermediates which underwent cyclization to (3R)-3-alkyl-4,l-benzoxazepin-2,5-diones... 

Scheme 62 BF3-Et20-catalyzed alkylation through highly activated alkenyl-oxocarbenium intermediates...

A metal-mediated rearrangement of 3-alkynyl flavone ethers has been found to involve 5-endo enyne cyclization to a platinum-containing spiro-oxocarbenium intermediate which may be trapped with methanol to give spirodihydrofurans or further rearranged to allenyl chromanediones or benzofuranones (Scheme 150). ... 

In 2007, a gold(I)-catalyzed cascade reaction of diynes and electron-rich aromatics and heteroaromatics for the synthesis of complex a-pyrones was successfully realized by Schreiber and Luo (Scheme 12.13) [16]. This reaction involves the [3,3]-sigmatropic rearrangement of the diynes 25 to an yne-allene intermediate 26, which is supported by the observed racemization of enan-tioenriched substrates. Gold(I)-induced a 6-endo-dig cyclization of intermediate 26 would give the oxocarbenium intermediate 27, which could be trapped by electron-rich aromatics and heteroaromatics to afford complex a-pyrones 28. 

The role as glycosyl donor proceeds through the standard oxocarbenium intermediate 2, which can be trapped by nucleophiles. In aqueous medium the product is an aldose (1, Nu = OH). When such oxidative hydrolyses were probed it was found that with C2-OAcyl substrates the reaction occurs much more slowly than with C2-OAlkyl. This observation has been introduced into a chemoselective coupling [3] protocol that has come to be known as the armed-disarmed strategy. [4] Thus as illustrated in Scheme 4a, the partners 10 and 11 gave disaccharide 12a, with no evidence of the product of self-coupling of 11, nor of further reaction of disaccharide 12a with the acceptor 11, both of which would have occurred at disarmed anomeric... 

A similar approach was taken by Ito and Ogawa who introducedp-methoxybenzyl (PMB) as carbon tether [7], Alcohols protected with PMB, e.g. 6, can be oxidatively deprotected with DDQ [8] or CAN [9] presumably via the oxocarbenium intermediate 7 (Scheme 3). 

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