Protic solvent-promoted reactions

Reaction of a stable carbene with iodine results in compound 46, which can be considered an isolated transition state which models the nucleophilic attack of the carbene on the iodine molecule (Scheme 25).55 The iodine-iodine bond js significantly lengthened and the carbon iodine bond distance of 2.104(3) A is slightly elongated when compared to that of iodoarenes. The authors report that protic solvents promote ionic dissociation to the 2-iodoimidazolium ion which is isoelectronic with the tellerium adduct 44. 

Aluminum chloride dissolves readily in chlorinated solvents such as chloroform, methylene chloride, and carbon tetrachloride. In polar aprotic solvents, such as acetonitrile, ethyl ether, anisole, nitromethane, and nitrobenzene, it dissolves forming a complex with the solvent. The catalytic activity of aluminum chloride is moderated by these complexes. Anhydrous aluminum chloride reacts vigorously with most protic solvents, such as water and alcohols. The ability to catalyze alkylation reactions is lost by complexing aluminum chloride with these protic solvents. However, small amounts of these "procatalysts" can promote the formation of catalyticaHy active aluminum chloride complexes. 

Alkali moderation of supported precious metal catalysts reduces secondary amine formation and generation of ammonia (18). Ammonia in the reaction medium inhibits Rh, but not Ru precious metal catalyst. More secondary amine results from use of more polar protic solvents, CH OH > C2H5OH > Lithium hydroxide is the most effective alkah promoter (19), reducing secondary amine formation and hydrogenolysis. The general order of catalyst procUvity toward secondary amine formation is Pt > Pd Ru > Rh (20). Rhodium s catalyst support contribution to secondary amine formation decreases ia the order carbon > alumina > barium carbonate > barium sulfate > calcium carbonate. 

Protic solvents such as i-PrOH and t-BuOH favor the diastereoselectivity of the reaction of 3-hydroxy-2-pyrone with acrylates [49b]. Further examples of proton-promoted Diels-Alder reactions are reported in Section 4.8. 

The synthesis and olefin metathesis activity in protic solvents of a phosphine-free ruthenium alkylidene bound to a hydrophilic solid support have been reported. This heterogeneous catalyst promotes relatively efficient ring-closing and cross-metathesis reactions in both methanol and water.200 The catalyst-catalyzed cross-metathesis of allyl alcohol in D20 gave 80% HOCH2CH=CHCH2OH. 

Interestingly, the same authors [13b] have isolated the l,2-dihydro-l,2,4,5-tetra-zine intermediate 21 by condensation of 2-cyanopyridine 20 with hydrazine hydrate in presence of flower of sulfur (Scheme 8.9 b). The reaction time is reduced under the action of microwave irradiation (125 W) protic solvents also promote the transformation. 

In an effort to obtain a salvinorin derivative possessing an oe-diol system which can be transformed into the dibenzoate ester required for the exciton chirality CD method, salvinorin A (1) or B (2) was treated with sodium borohydride in various protic solvents. The products having the la,2a-diol group were obtained in high yield. However, this reduction was accompanied by extensive isomerization at C-8. While mechanistic details for this unexpected observation remain to be established at this time, the isomerization at C-8 appears to be the result of the base-promoted clevage of the C-8/9 bond under the reaction conditions followed by the reclosure to provide the 8-epimer prior to the reduction of the 1-ketone. Furthermore, attempts to obtain the 1,2-dibenzoate derivative of the major reduction product 3 under various benzoylating conditions invariably produced only the 2-monobenzoate. 

In 2006, Yu et al. combined pyridinyl-directed C-H activation and C-C bond formation with alkylboronic acids (see Section 10.5.4.2).23 The success of this transformation relied on the combination of palladium acetate (10 mol%), benzoquinone (1 equiv), and silver oxide or carbonate (0.5 equiv) in a protic solvent, but an excess of boronic acid (3 equiv) was required (Scheme 10.9). Interestingly, in this reaction silver oxide played a dual role as promoter for the transmetallation step and as cooxidant with benzoquinone. 

In another protocol using a ruthenium(pyridinebisoxazoline)(pyridinedicarboxylic acid) catalyst 26 and iodosylbenzene as the terminal oxidant, Seller and co-workers <03TL7479> found that the addition of water and protic solvents resulted in a 100-fold acceleration of the epoxidation, presumably due to a ligand dissociation effect that promotes the oxidation of the ruthenium catalyst. Thus, the conversion of rrans-stilbene 27 to the corresponding 5,S-epoxide 28 required 96 h in anhydrous toluene, but only 1 h in the presence of r-butanol and water. The enantioselectivity of the reaction was not significantly affected (63% and 57% ee, respectively). 

Thiazoles are deactivated towards electrophilic substitution, and thus direct reaction with hydride re-ductants to give thiazolines should be facilitated. There are indeed some examples of this type of reaction, but it is more common to reduce N-alkylated thiazolium salts (209). These compounds are converted first by reaction with sodium borohydride into 4-thiazolines (210), which in protic solvents become protonated and undergo further reduction to yield thiazolidines (211). Similarly the isoquinoli-nium salt (213), formed by the acid-promoted cyclization of the isoquinoline (212), is converted into the tetrahydroisoquinoline (214) (presumably via an intermediate 1,2-dihydroisoquinoline) by reaction with sodium borohydride. ... 

The EPD solvents of high Lewis basicity include the most common dipolar non-HBD solvents (e.g., DMSO. acetonitrile, DMF, acetone, HMPA, etc.) and some open-chain polyethers (oligoethylene glycol dialkyl ethers 1 ( glymes ). They specifically solvate the cation but weakly interact with the anion and, for this reason, are found to enhance nucleophilicity and basicity of anion-promoted reactions in comparison with the reactivity realized in protic HBD media. ... 

---