Tetrazole-catalyzed reaction

With these fundamental studies complete, we turned our attention to the adaptation of the method for a site-selective catalysis/deoxygenation sequence [119]. Koreeda and Zhang reported the use of iodoarene-functionalized phosphites as good substrates for deoxygenation [120]. We set out to adapt this work to an Atz-based peptide-based catalytic reaction. Phosphoramidite 68 (Scheme 8) was readily prepared, and fotmd to behave in tetrazole-catalyzed reactions. Its derivatives, upon exposure to appropriate conditions, enabled deoxygenation of a number of alcohols in analogy to literature precedents see [119] for details. 

Aryl and vinyl nitriles have been prepared very efficiently from the corresponding bromides by palladium-catalyzed reactions under microwaves. This energy source has been employed for the conversion of these nitriles into aryl and vinyl tetrazoles by cycloaddition reactions with sodium azide (Scheme 9.66). The direct transformation of aryl halides to the aryl tetrazoles in a one pot procedure could be accomplished both in solution and on a solid support [115], The reactions were complete in a few minutes, a reaction time considerably shorter than those previously reported for the thermal reactions. The cydoadditions were performed with sodium azide and ammonium chloride in DMF and, although no explosion occurred in the development of this work, the authors point out the necessity of taking adequate precautions against this eventuality. 

Odedra A, Seeberger PH (2009) 5-(Pyrrolidin-2yl)tetrazole-catalyzed aldol and Mannich reactions acceleration and lower catalyst loading in a continuous-flow reactor. Angew Chem Int Edit 48(15) 2699-2702... 

Some heterocycles can be linked to supports as tetrahydropyranyl derivatives. Attachment of indoles, purines, or tetrazoles (Table 3.29) has been achieved by treatment of a support-bound dihydropyran with the heterocycle in the presence of catalytic amounts of pyridinium tosylate [487], camphorsulfonic acid [539], or TFA [540] in DCE at 60-80 °C for 16-24 h. Indole-derived orthoesters, such as that in Entry 7 (Table 3.29), can be prepared by heating the indole with triethyl orthoformate (160 °C, 24 h) followed by acid-catalyzed reaction of the resulting orthoester with a resin-bound diol [541,542], As illustrated by Entry 8 (Table 3.29), indoles can also be linked to the Wang resin or related supports as carbamates. Cleavage by TFA is, how-... 

A somewhat different but mechanistically related reaction is the [2 -f 3] cycloaddition of a functionalized alkyne or nitrile to an azide to form a disubstituted triazole (120) or tetrazole ring (121, 122), linking the respective functionalities irreversibly (Scheme 14b). This click chemistry was used by Sharpless and co-workers (120) in 2001 as a tool to probe biochemical catalysis and substrate activation. The ease of the Cu(I)-catalyzed reaction has created a true explosion (120-160) of simple coupling-functionalization chemistry of all types of biochemical components (sugars, DNA, proteins, enzymes, substrates, inhibitors) (131, 135, 136, 139, 142, 155, 157-160), polymers (126, 134, 140, 147, 154),... 

Figure 7 illustrates the different steps in solid support synthesis of an oligonucleotide. After detritylation, tetrazole-catalyzed coupling - the most crucial reaction step - is carried out. Figure 8 indicates the mechanism of tetrazole action. 

Two different models were proposed by Ley for the 2b-catalyzed reaction which should also be of application for the cases of proline 1 and proline-tetrazole catalysts 2a, both of them in good agreement with the observed absolute configuration of the final Michael adducts (Figure 2.2). One proposal involved the possibility of the tetrazole moiety acting as a bulky substituent which directed the income of the electrophile by the less hindered face of the enamine intermediate in the most stable pseudo-rrarw conformation. Alternatively, the formation of a hydrogen-bonded transition state was also proposed, in this case with the participation of the pseudo-cj5 enamine conformer. This second pathway was afterwards estimated to be the energetically most favored one by DFT calculations. ... 

Once in the modern organocatalysis era and with the mechanistic rationale for the iminium activation concept in hand, many different and more efficient methodologies have been developed for this particular reaction. For example, and still focused on the use of secondary amines as catalysts, imidazolidine 53a and proline-tetrazole 2a catalysts have been developed for the conjugate addition of malonates to acyclic enones (Scheme 3.17). For the 53a-catalyzed reaction, this proceeded well in terms of yields and enantioselectivities for a wide range of differently substituted arylideneacetones and for cyclohexenone but yields tend to decrease when more bulky substituents were placed around the carbonyl moiety. Importantly, the enantioselectivity of the reaction was very dependent upon the nature of the malonate reagent, observing that dibenzyl malonate and diethylmalonate furnished the best results. The most... 

Most of the described procedures of forming tetrazoles (catalyzed and uncatalyzed) suffer from some disadvantages hke the use of both toxic metals and expensive reagents, drastic reaction conditions, water sensitivity, and the presence of dangerous hydrazoic acids. The zinc(II)-catalyzed reactions to form tetrazoles by Sharpless and coworkers [212,224,225] are safe, but in the case of stericaUy hindered aromatic or alkyl inactivated nitriles, high temperatures (140-170 °C) are required. Amantini et aL reported TBAF to be an efficient catalyst in the synthesis of 5-substituted IH-tetrazoles by using TMSN3 without solvents (Scheme 65) [226]. 

Additionally, for catalyzed reactions, an example for synthesis of tetrazoles by reacting isonitriles and azides was reported. Yamamoto et aL reported that the acid-catalyzed [3-1-2] cycloaddition between isocyanides 322 and trimethylsUyl azide (146) in the presence of methanol gives the desired 1-substituted tetrazoles 323 in good yields (Scheme 68) [ 177-179). 

The same Lewis acid-catalyzed reaction of the cyanosilylation of aromatic aldehydes was investigated by Long et al. [85]. The catalytic activity of the sodalite-type compound Mn3[Mn Cl3(btt)g(CH30H),Q] (BTT is l,3,5-benzene-tris(tetrazol-5-yl)) was studied. This material is a 3D porous structure with a pore diameter of 1 nm. It was assumed that each of the two types of Mn(II) sites exhibits catalytic activity. The distinctive features of this catalyst are the high conversions in the case of small substrates and a good substrate size selectivity, properties that are consistent with the occurrence of the catalytic process in the channels. The surface of the framework bears open Mtf+ ions, which act as Lewis acid sites. 

Scheme 24.4 Proline-tetrazole catalyzed aldol reactions.

The disadvantage of this method is that the dichloridites and monochloridites are sensitive to water and thus could not be used readily in automated oligonucleotide synthesis. This problem was overcome by Beaucage and Caruthers, who developed the phosphoramidite approach. In this method, derivatives of the form R 0P(NR2)2 react with one equivalent of an alcohol (catalyzed by species such as l//-tetrazole) to form diesters, R OP(OR")NR2, which usually are stable, easily handled solids. These phosphoroamidites are easily converted to phosphite triesters by reaction with a second alcohol (catalyzed by l//-tetrazole). Here, again, oxidation of the phosphite triester with aqueous iodine affords the phosphate triester. Over the years, numerous protective groups and amines have been examined for use in this approach. Much of the work has been reviewed. ... 

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