Hydride compounds synthetic equivalents

A somewhat related microwave-promoted 5 -0-allylation of thymidine has been described by the Zerrouki group (Scheme 6.108) [215], While the classical method for the preparation of 5 -0-allylthymidine required various protection steps (four synthetic steps in total), the authors attempted the direct allylation of thymidine under basic conditions. Employing sodium hydride as a base at room temperature in N,N-dimethylformamide resulted in the formation of per-allylated compounds along with the desired monoallylated product (75% yield). The best result was achieved when both the deprotonation with sodium hydride (1.15 equivalents) and the subsequent allylation (1.2 equivalents of allyl bromide) were conducted under... 

We now tum our attention to the C21-C28 fragment 158. Our retrosynthetic analysis of 158 (see Scheme 42) identifies an expedient synthetic pathway that features the union of two chiral pool derived building blocks (161+162) through an Evans asymmetric aldol reaction. Aldehyde 162, the projected electrophile for the aldol reaction, can be crafted in enantiomerically pure form from commercially available 1,3,4,6-di-O-benzylidene-D-mannitol (183) (see Scheme 45). As anticipated, the two free hydroxyls in the latter substance are methylated smoothly upon exposure to several equivalents each of sodium hydride and methyl iodide. Tetraol 184 can then be revealed after hydrogenolysis of both benzylidene acetals. With four free hydroxyl groups, compound 184 could conceivably present differentiation problems nevertheless, it is possible to selectively protect the two primary hydroxyl groups in 184 in... 

Acyl radicals are very useful synthetic intermediates. Their preparation is not simple since the corresponding halides are highly electrophilic and cannot be used as radical precursors. Organocobalt compounds were proposed as suitable source of acyl radicals [44]. However, the use of acyl selenides proved to be more general [45, 46]. These radical precursors can be efficiently prepared from the corresponding carboxylic acids and esters [47]. Acyl phenyl selenides should be preferred, when possible, relative to acyl methyl selenides due to the consumption of two equivalents of tin hydride with this last system (Scheme 1) [4]. Acyl selenides have found many applications in tandem radical additions to alkenes. Examples of intermole-cular [Eq. (18)] [48,49] and intramolecular reactions [Eq. (19)] [50a] are reported. The enoyl selenide 68 give the unsaturated acyl radicals 69. This intermediate... 

The hydride-donating potential of 1,4-dihydropyridines has already been discussed in a mechanistic context in Section 1.3.2.3. Commonly available 1,4-dihydropyridines are the Hantzsch esters (7 X = OR), obtained from condensation of a -keto ester with ammonia and an aldehyde. By far the simplest syntheses of Hantzsch esters involve condensation of ammonia (substituted amines react in general poorly) and an aldehyde if a hydride equivalent at the 4-position is desired. The Hantzsch synthesis has been used in many guises, also to produce nonsymmetrical systems. The interest in these compounds as calcium antagonists has doubtless stimulated the extensive synthetic effort. ... 

Nucleophiles used in the seminal papers by Tsuji and co-workers were mostly stabilized carbon nucleophiles, and the method found an early synthetic application in a preparation of steroids." It soon became evident that many other types of nucleophiles could be used. In particular, hydride ion equivalents led to l-olefinsf ° " (see Sect. V.2.3.1), Silyl and stannyl enolates of simple ketones and aldehydes and esters can be aUylated, as well as allyl enol carbonates (see Sect. V.2.1.4), This is an indirect a-aUylation of ketones, aldehydes, and esters. Enol derivatives can take another reaction course under Pd(0) catalysis (Scheme 2). Thus, oxidation to a,/3-unsaturated carbonyl compounds ensues if reactions are performed in acetonitrile under precise sources of catalyst precursor. "" "" A full discussion on the dichotomy of allylation-oxidation has been published, as well as a comparison of the usefulness of several transition metals as catalysts in allylation of nucleophiles. ... 

According to low temperature C-NMR study on the affinity of MAD with oxygen containing functional groups, such as carbonyl compounds and ethers, coordination of amides to MAD is stronger than that of aldehydes, ester, and ketones, while coordination of ethers is rather weak [46). One of the most important synthetic utilities of MAD is that in the hydride reduction of two different ketones MAD can protect the less hindered ketone or more basic ketones by forming complexes with these ketones, that is, selective reduction of more hindered free ketones can realize. As shown in Scheme 6.38, for example, DIBAL reduction (1 equivalent) of a 1 1 mixture of acetophenone and tert-butylphenylketone provide two carbinols with low chemoselectivity. On the other hand, in the presence of... 

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