Uncatalyzed synthesis

In light of these results the reported uncatalyzed synthesis of 1,2-dilithioethane 7 in 27-30% yield from ethylene and lithium powder in dioxane as the solvent should be reproduced, inasmuch as characterization was only by hydrolysis to yield ethane. 

The sequence below is written to illustrate hydrolysis but the reverse represents the (uncatalyzed) synthesis of CS and similar a,(3-unsaturated dinitriles (Corson and Stoughton, 1928). 

Heijkants RGJC, Van Calck RV, Van Tienen TG, De Groot JH, Buma P, Pennings AJ, et al. Uncatalyzed synthesis, thermal and mechanical properties of polyurethanes based on poly(E-caprolactone) and 1,4-butane diisocyanate with uniform hard segment. Biomaterials 2005 26 4219-28. 

Azizi, N., Ebrahimi, F., Aakbari, E., Aryanasab, F., and Saidi, M. R. (2007). Waste-free and environment-friendly uncatalyzed synthesis of dithiocarbamates under solvent-free conditions. Synlett, 2797-2800. 

SCHEME 4.91 Ultrasound-assisted uncatalyzed synthesis of a-aminophosphonates [164],... 

The uncatalyzed thermolysis of hydrazone (24) gave, among other products, an indole by loss of the ortho F in a mirror image of the usual Fisher indole synthesis [83JCS(P1)821]. 

W. R. Roush in Allylorganometallics The Uncatalyzed Reaction of Allylorganometallics with C = X Electrophiles in Comprehensive Organic Synthesis, C. H. Heathcock, Ed., Vol. 2, Perga-mon. Oxford 1991. 

The aqueous aza-Diels-Alder reaction of an aldehyde and an amine hydrochloride with a diene is catalyzed by lanthanide(III) trifluoromethane sulfonates (Ln(OTf)3, triflates [24]). Some examples are reported in Schemes 6.12 and 6.13. With respect to uncatalyzed reactions, the lanthanide catalyst allows milder reaction conditions, increases the reaction yield and does not affect the diaster-eoselectivity of the reaction, but influences the regiochemistry as in the cycloaddition of 25 with 1,3-dimethyl-1,3-butadiene (Schemes 6.10 and 6.12). These results have been applied [24b-d] to the synthesis of azasugars (Scheme 6.14). 

Metal-catalyzed hydrophosphination has been explored with only a few metals and with a limited array of substrates. Although these reactions usually proceed more quickly and with improved selectivity than their uncatalyzed counterparts, their potential for organic synthesis has not yet been exploited fully because of some drawbacks to the known reactions. The selectivity of Pt-catalyzed reactions is not sufficiently high in many cases, and only activated substrates can be used. Lanthanide-catalyzed reactions have been reported only for intramolecular cases and also sulfer from the formation of by-products. Recent studies of the mechanisms of these reactions may lead to improved selectivity and rate profiles. Further work on asymmetric hydrophosphination can be expected, since it is unlikely that good stereocontrol can be obtained in radical or acid/base-catalyzed processes. 

Quinone methides have been shown to be important intermediates in chemical synthesis,1 2 in lignin biosynthesis,3 and in the activity of antitumor and antibiotic agents.4 They react with many biologically relevant nucleophiles including alcohols,1 thiols,5-7 nucleic acids,8-10 proteins,6 11 and phosphodiesters.12 The reaction of nucleophiles with ortho- and /iara-quinone methides is pH dependent and can occur via either acid-catalyzed or uncatalyzed pathways.13-17 The electron transfer chemistry that is typical of the related quinones does not appear to play a role in the nucleophilic reactivity of QMs.18... 

While in the uncatalyzed reaction of l-ethyleneimino-2-hydroxy-3-butene in THF, refluxing for four hours was necessary to produce 70% of the ester, in the presence of NaNH2 a 90% yield was achieved at room temperature after only five minutes.[13 14] An especially interesting example of the use of the imidazolide method for ester synthesis is illustrated by the total synthesis of actinomycin C3.[15],[16] Working with N-protected L-TV-methylvaline and CDI, esterification of the hydroxyl group on the threonine residue proved successful whereas this could not be accomplished by any of the conventional methods. 

In contrast to thermal uncatalyzed reactions of /V-acylsulfinylamines with aryl isocyanates which give rise to azoarenes,188 the cobalt or iron carbonyl-catalyzed process gives additionally 3,5-dioxo-l,2,4-triphenyl-1,2,4-triazolidine (Scheme 124).189 The only possible restriction on this simple urazole synthesis would be the expectation that the substituents on the reactants must be the same to prohibit exchange. 

The availability of oxepins that bear a side chain containing a Lewis basic oxygen atom (entry 2, Table 6.4) has further important implications in enantioselective synthesis. The derived alcohol, benzyl ether, or methoxyethoxymethyl (MEM) ethers, in which resident Lewis basic heteroatoms are less sterically hindered, readily undergo diastereoselective uncatalyzed alkylation reactions when treated with a variety of Grignard reagents [17]. The examples shown below (Scheme 6.7) demonstrate the excellent synthetic potential of these stereoselective alkylations. 

Accordingly, phosphoric acid mono- and di-esters permit uncatalyzed glycosyl transfer from 0-(glycosyl)trichloroacetimidates (52a,55-57,58a,58b). The reaction is thus very useful in the synthesis of glycophos-pholipids (1,55), which are important constituents of cell membranes (1). Commonly, direct phosphorylation at the anomeric hydroxyl group leads to... 

The acylated peptides (Myr)GCX-Bimane 31 a-e (X = G, L, R, T, V), which are found in certain nonreceptor tyrosine kinases and ct-subunits of several heterotrimeric G-proteins, were synthesized in solution using common solution-phase peptide synthesis with X-myristoylglycine as a building block. These model peptides were used for acylation studies with palmitoyl-CoA in phospholipid vesicles at physiological pH. For such uncatalyzed spontaneous reactions only a modest molar excess of acyl donor species (2.5 1) was necessary. Unprotected side chains of threonine or serine are not interfering with this S-acylation (Scheme 14). 

Di Salvo A, Spanedda MV, Ourevitch M, Crousse B, Bonnet-Delpon D (2003) Uncatalyzed domino reaction in hexafluoroisopropanol a simple protocol for the synthesis of tetrahydroquinoline derivatives. Synthesis 14 2231-2235... 

Uncatalyzed addition reactions of Grignard reagents with nonconjugated alkenes and aUcynes are of limited use in synthesis. However, carbon-carbon double bonds substituted by a leaving group, such as an acetate, are susceptible to be displaced by organomagnesium compounds presumably by an addition-elimination pathway. A few examples have been reported (equation 64). 

Pyrroles and their Benzo Derivatives (iii) Synthesis and Applications Table 10 Uncatalyzed Acylation of Pyrrole and Indole... 

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