Free secondary

The experimental details describe the use of a free secondary amine for the preparation of a nitrosainine. Identical results are, of course, obtained by employing solid diethylamine hydrochloride. 

The 6-endo activated epoxy alcohol cyclization process was also expected to play a central role in the annulation of pyran ring G of the natural product (see Scheme 22). Silylation of the free secondary hydroxyl group in compound 131 furnishes, after hydrobora-tion/oxidation of the double bond, compound 132. Swern oxidation of alcohol 132 produces an aldehyde which reacts efficiently with (ethoxycarbonylethylidene)triphenylphosphorane in the presence of a catalytic amount of benzoic acid in benzene at 50 °C, furnishing... 

With ring G in place, the construction of key intermediate 105 requires only a few functional group manipulations. To this end, benzylation of the free secondary hydroxyl group in 136, followed sequentially by hydroboration/oxidation and benzylation reactions, affords compound 137 in 75% overall yield. Acid-induced solvolysis of the benzylidene acetal in 137 in methanol furnishes a diol (138) the hydroxy groups of which can be easily differentiated. Although the action of 2.5 equivalents of tert-butyldimethylsilyl chloride on compound 138 produces a bis(silyl ether), it was found that the primary TBS ether can be cleaved selectively on treatment with a catalytic amount of CSA in MeOH at 0 °C. Finally, oxidation of the resulting primary alcohol using the Swem procedure furnishes key intermediate 105 (81 % yield from 138). 

In the synthesis of the squalenoid glabrescol (72 originally attributed structure), containing five adjacent (all cis) THF rings, the necessary precursor of the polyepoxide cascade, the pentaepoxide 71, was achieved by epoxidation of each of the trisubstituted double bonds of the known (R)-2,3-dihydroxy-2,3-dihydrosqualene (70) by the Shi epoxidation approach (Scheme 8.18) [34]. Treatment of 71 with CSA at 0 °C and subsequent purification by column chromatography provided the pure polycyclic ether 72 by a cascade process reasonably initiated by the free secondary alcohol functionality [35a]. 

The final example in this section is the synthesis of a tristetrahydrofuran 2-606 described by the group of Rychnovsky [313]. Here, the tris(sulfate) 2-605 was converted into 2-606 by simply heating it in a mixture of MeCN and H20 (Scheme 2.138). The domino reaction is most likely initiated by deprotection of the primary alcohol, which then attacks the adjacent sulfonate unit in a SN2-type manner to afford the first furan moiety. Under the reaction conditions the formed acyclic sulfate is hydrolyzed affording a free secondary alcohol which then attacks the next adjacent cyclic sulfate unit. Overall, the SN2/hydrolyzation sequence proceeds three times to finally provide the poly(tetrahydrofuran) 2-606 as a single isomer in 93 % yield. 

To create the free secondary amine group (N-H) fulleropyrrolidine, an amine-protected starting material can be used in the reaction (Cai et al., 2006). For instance, a trityl-oxazolidinone (using either triphenylmethyl- or better, 4-methoxytriphenylmethyl-protecting groups) can be reacted with C60 to yield the trityl-protected pyrrolidine (Figure 15.5). 

Although the ruthenium allenylidene complexes 2 have not yet been as comprehensively studied as their carbene counterparts, they also seem to exhibit a closely related application profile [6]. So far, they have proven to tolerate ethers, esters, amides, sulfonamides, ketones, acetals, glycosides and free secondary hydroxyl groups in the substrates (Table 1). 

Nickel—hydrogen batteries offer long cycle life that exceeds that of other maintenance-free secondary battery systems and accordingly makes it suitable for many space applications. Three types of separator materials have been used for aerospace Ni—H2 cells— asbestos (fuel-cell-grade asbestos paper), Zircar (untreated knit ZYK-15 Zircar cloth),and nylon. 

It is very important in PAP techniques for the secondary antibody to be applied in excess. This way, one arm of the divalent Fab portion of the immunoglobulin molecule can bind the primary antibody, and the other arm is free to bind the PAP complex. If not in excess, both arms of the molecule may bind the primary antibody, creating a prozone-type of effect. Without a free secondary antibody Fab site to capture the PAP complex, the assay will not work. 

The nature of the aromatic substituents is apparently not critical for SSRI activity, as indicated by the structure of duloxetine (23-5), where one ring is replaced by thiophene and the other by naphthalene. The synthesis starts as above by the formation of the Mannich base (23-1) from 1-acetyl thiophene with formaldehyde and dimethyl-amine. Treatment of that intermediate with the complex from lithium aluminum hydride and the 2R,3S entantiomer of dimethylamino-l,2-diphenyl-3-methyl-butane-2-ol gives the S isomer (23-2) in high enantiomeric excess. Treatment of the aUcoxide from (23-2) and sodium hydride with 1-fluoronaphthalene leads to the displacement of halogen and thus the formation of ether (23-2). The surplus methyl group is then removed by yet another variant of the von Braun reaction that avoids the use of a base for saponifying the intermediate urethane. Thus, reaction of (23-3) with trichloroethyl formate leads to the A -demethylated chlorinated urethane (23-4). Treatment of that intermediate with zinc leads to a loss of the carbamate and the formation of the free secondary amine duloxetine (23-5) [23]. 

If the secondary sulfonyloxy group is trans to two free (or potentially free), secondary hydroxyl groups, both of which are contiguous to it, two... 

However, if the secondary sulfonyloxy group is cis to one contiguous, free secondary hydroxyl group (or, if feasible, to two), anhydro-ring formation obviously cannot take place with Walden inversion, and so neither anhydro-ring formation nor Walden inversion occurs.311 Such desul-fonylations are usually achieved only under drastic hydrolytic conditions. 

If the secondary sulfonyloxy group is not isolated and is trans to a single, contiguous, free (or potentially free) secondary hydroxyl group, the intermediate formation of an anhydro ring occurs (as previously described in reference to anhydro-ring formation with sodium hydroxide and sodium methoxide see p. 172). Ammonia then causes ring scission as follows ... 

The same system improves the yields of /J-D-mannopyranosidcs in reaction of 2,3 4,6-di-0-cyclohexylidine-a-D-mannopyranosyl chloride, particularly with carbohydrates with a single free secondary hydroxyl group.2... 

Reductive iodination of this vinylalane intermediate with IV-iodosuccinimide (NIS) yields the Z-trienyl iodide. Finally the free secondary alcohol is protected as TBS ether in a standard procedure to provide 8. 

As depicted in Scheme 13, the SnCU-promoted vinylogous aldol reaction between silyloxy pyrrole 76 and D-glyceraldehyde 11 afforded the unsaturated lactam 77 in a good yield and excellent diastereoselectivity. Saturation of the carbon-carbon double bond within 77 using the NiC /NaBfLt mixture, followed by protection of the free secondary carbinol group as a TBS-ether and TV-Bn for TV-Boc protecting... 

The selected example, by An et al. [20], reported the use of novel polyazapyridinophanes scaffolds to prepare medium size solution pool libraries via solution-phase simultaneous addition of functionalities (SPSAF). The synthesis of the scaffolds is reported in Figure 7.3. The unsymmetrical 13-, 14-and 15-member scaffolds were prepared from the corresponding polyamines, bearing two free secondary amines, with either very similar 1, 2 or completely... 

Any substitution reaction (i.e. by tertiary or secondary amines or by metallated secondary amines) is greatly facilitated when the jS-carbon carries an electron-with-drawing or simply a conjugative group. Accordingly, chlorocyanoacetylene reacts smoothly at —50° with free secondary amines to cyanoynamines, an example of push-pull substituted acetylenes (12)27... 

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