Nucleophilic participation Subject

During the past few years, increasing numbers of reports have been published on the subject of domino reactions initiated by oxidation or reduction processes. This was in stark contrast to the period before our first comprehensive review of this topic was published in 1993 [1], when the use of this type of transformation was indeed rare. The benefits of employing oxidation or reduction processes in domino sequences are clear, as they offer easy access to reactive functionalities such as nucleophiles (e. g., alcohols and amines) or electrophiles (e. g., aldehydes or ketones), with their ability to participate in further reactions. For that reason, apart from combinations with photochemically induced, transition metal-catalyzed and enzymatically induced processes, all other possible constellations have been embedded in the concept of domino synthesis. 

The participation of the germanium dimers in nucleophilic/electrophilic or Lewis acid/base reactions has been the subject of several investigations on the Ge(100)-2x1 surface [16,49,255,288,294,313-318]. As for the case of silicon, adsorption of amines has provided an excellent system for probing such reactions. Amines contain nitrogen lone pair electrons that can interact with the electrophilic down atom of a tilted Ge dimer to form a dative bond via a Lewis acid/base interaction (illustrated for trimethylamine at the Si(100)-2 x 1 surface in Ligure 5.17). In the dative bond, the lone pair electrons on nitrogen donate charge to the Ge down atom [49]. 

In an effort to provide experimental evidence for the formation of a second oxyallyl cationic intermediate, a gem-dichlorocyclopropane substrate was envisaged with two internal nucleophiles one to participate in the initial interrupted Nazarov reaction, and the other to capture the second cationic species. Surprisingly, when the carefully designed substrate 80 was subjected to the optimized reaction conditions, an alternate mode of trapping occurred to generate the intriguing bridged bicyclic product 81 (Scheme 4.25). 

An obvious starting point was to look for general acid catalysis of the attack of nucleophiles on a methyoxymethyl acetal known to be subject to efficient carboxyl-catalyzed hydrolysis. Participation by nucleophiles other than water in the hydrolysis of the salicylic acid derivative 3.17 could not be convincingly distinguished from specific salt effects (the range of nucleophiles is limited by the requirement that the COOH group (pKa 3.77) be protonated) [49]. On the other hand there is clear involvement of nucleophiles, including carboxylate anions, in the reaction of the dimethylammonium system 3.18 [44] (Scheme 2.24). The difference is presumably simply quantitative. 

The ozonolysis reaction has been the subject of considerable mechanistic study. It is likely that in most cases the reaction proceeds by breakdown of the 1,3-dipolar cycloaddition product to a carbonyl oxide 99 and an aldehyde (or ketone) (5.99). The fate of the carbonyl oxide depends on the solvent and on its structure and the structure of the carbonyl compound. In an inert (non-participating) solvent, the carbonyl compound may react with the carbonyl oxide to form an ozonide 100 otherwise the carbonyl oxide may dimerize to the peroxide 101 or give ill-defined polymers. In nucleophilic solvents such as methanol or acetic acid, hydroperoxides of the type 102 are formed. 

The methanol can be replaced by other nucleophilic solvents such as ethanol, acetic acid, or water (in tetrahydrofuran as cosolvent) to give the corresponding ethoxy-, acetoxy-, or hydroxy-esters. Cyclic ethers (substituted tetrahydrofurans and tetrahydropyrans) are formed by intramolecular reaction when the unsaturated ester also contains an appropriately placed hydroxy-group, even in the presence of a reactive solvent. This has been developed into a procedure for the identification, analysis, and isolation of long-chain alcohols and acids having alkene unsaturation in positions 3 (trans only), 4 (cis or tram), or 5 (cis or trans) Such acids (or natural mixtures in which they are present) are reduced to alcohols and subjected to oxymercuration (in DMF as a non-participating solvent) and demercuration. Cyclic ethers are formed only when there is unsaturation at positions 3,4, or 5 other double bonds are unaffected. For example, methyl arachidonatc... 

SOMO catalysis, which has been the subject of considerable attention in recent years, is a unique and versatile activation mode that can participate in bond construction with various n-rich nucleophiles. The first asymmetric intramolecular a-arylation of aldehydes was reported by Nicolaou in 2009 using organo-SOMO catalysis [17a]. The authors applied imidazolidinone 23 as catalyst and cerium ammonium nitrate (CAN) as the oxidant Various 5-oxopentylbenzenes 36, or indole derivatives 38, could furnish the cyclic products 37 or 39, respectively, in good yields and with excellent ees (Scheme 36.11). Later, MacMillan disclosed similar research [17b], and a theoretical study of the intramolecular a-arylation of aldehydes was also reported by the same group via density functional theory [17c],... 

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