Alcohols tert., 2-functionalized

Figure 7. Salting-out coefficient B as a function of weight-percent alcohol tert-Butanol temperatures (D), 25°C (O), 35°C (A), 45°C. Ethanol temperatures (+), 25°C (X), 35°C (0 ), 45°C.

In one specific report [62] the reaction of bromocyclopentane with magnesium was studied in the presence of the radical trap 2,2,6,6-tetra-methylpiperidine nitroxyl (TMPO) and tert-hulyl alcohol which functions as a proton donor. 

Step 3 in Figure 5 6 shows water as the base which ab stracts a proton from the car bocation Other Bronsted bases present in the reaction mixture that can function in the same way include tert butyl alcohol and hydrogen sulfate ion... 

The oxirane ring in 175 is a valuable function because it provides a means for the introduction of the -disposed C-39 methoxy group of rapamycin. Indeed, addition of CSA (0.2 equivalents) to a solution of epoxy benzyl ether 175 in methanol brings about a completely regioselective and stereospecific solvolysis of the oxirane ring, furnishing the desired hydroxy methyl ether 200 in 90 % yield. After protection of the newly formed C-40 hydroxyl in the form of a tert-butyldimethylsilyl (TBS) ether, hydrogenolysis of the benzyl ether provides alcohol 201 in 89 % overall yield. 

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). 

Provided an excess of the hydroperoxide is not used, sulfoxides are obtained in essentially quantitative yields in short reactions times, usually 0.7-2.5 h (42). The method is uncomplicated and can be carried out on the benchtop. The long shelf-life of 1 (> 3 months) adds to the convenience of this procedure. A wide variety of functional groups is tolerated on R and R. The reaction affords nearly pure sulfoxides without contamination from sulfones. The product is obtained simply be evaporating the solvent and tert-butyl alcohol. This method avoids aqueous workup, which is often required when peracids are used (43), and is thus convenient for water-soluble sulfoxides. 

Other functionalized supports that are able to serve in the asymmetric dihydroxylation of alkenes were reported by the groups of Sharpless (catalyst 25) [88], Sal-vadori (catalyst 26) [89-91] and Cmdden (catalyst 27) (Scheme 4.13) [92]. Commonly, the oxidations were carried out using K3Fe(CN)g as secondary oxidant in acetone/water or tert-butyl alcohol/water as solvents. For reasons of comparison, the dihydroxylation of trons-stilbene is depicted in Scheme 4.13. The polymeric catalysts could be reused but had to be regenerated after each experiment by treatment with small amounts of osmium tetroxide. A systematic study on the role of the polymeric support and the influence of the alkoxy or aryloxy group in the C-9 position of the immobilized cinchona alkaloids was conducted by Salvadori and coworkers [89-91]. Co-polymerization of a dihydroquinidine phthalazine derivative with hydroxyethylmethacrylate and ethylene glycol dimethacrylate afforded a functionalized polymer (26) with better swelling properties in polar solvents and hence improved performance in the dihydroxylation process [90]. 

Sodium and sodium amalgam may be used for reduction of amides but the yields of amines are generally very low. Primary aromatic amides (benz-amides) were reduced at the carbonyl function with 3.3 equivalents of sodium in liquid ammonia and ethanol while in tert-butyl alcohol reduction took place in the aromatic ring giving 1,4-dihydrobenzamides [984. ... 

Another route to a methyl-branched derivative makes use of reductive cleavage of spiro epoxides ( ). The realization of this process was tested in the monosaccharide series. Hittig olefination of was used to form the exocyclic methylene compound 48. This sugar contains an inherent allyl alcohol fragmenC the chiral C-4 alcohol function of which should be idealy suited to determine the chirality of the epoxide to be formed by the Sharpless method. With tert-butvl hydroperoxide, titanium tetraisopropoxide and (-)-tartrate (for a "like mode" process) no reaction occured. After a number of attempts, the Sharpless method was abandoned and extended back to the well-established m-chloroperoxybenzoic acid epoxida-tion. The (3 )-epoxide was obtained stereospecifically in excellent yield (83%rT and this could be readily reduced to give the D-ribo compound 50. The exclusive formation of 49 is unexpected and may be associated with a strong ster chemical induction by the chiral centers at C-1, C-4, and C-5. 

The alcohols used may also contain fairly sensitive functional groups, I. l.. esters, halides, silyl ethers, etc. In this work, therefore, tert-butyl toth ioacetate is behaving as a synthetic equivalent to diketene. When this... 

Di(tert-butyl)zinc reacts with a variety of terminal alkynes in refluxing THF (but not disubstituted ones), including those bearing functional groups such as alcohols, ethers, acetals or amines12. These additions are completely regioselective as the bulky tert-butyl group is delivered to the less substituted carbon, presumably for steric reasons. However,... 

Molybdenum-based catalysts are highly active initiators, however, monomers with functionalities with acid hydrogen, such as alcohols, acids, or thiols jeopardize the activity. In contrast, ruthenium-based systems exhibit a higher stability towards these functionalities (19). An example for a molybdenum-based catalyst is (20) MoOCl2(t-BuO)2, where t-BuO is the tert-butyl oxide radical. The complex can be prepared by reacting M0OCI4 with potassium tert-butoxide, i.e., the potassium salt of terf-butanol. 

Asymmetric Epoxidation. Asymmetric epoxidation of nonfunctionalized alkenes manifests a great synthetic challenge. The most successful method of asymmetric epoxidation, developed by Katsuki and Sharpless,332 employs a Ti(IV) alkoxide [usually Ti(OisoPr)4], an optically active dialkyl tartrate, and tert-BuOOH. This procedure, however, was designed to convert allylic alcohols to epoxy alcohols, and the hydroxyl group plays a decisive role in attaining high degree of enantiofa-cial selectivity.333,334 Without such function, the asymmetric epoxidation of simple olefins has been only moderately successful 335... 

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