Functionalized primary alcohols

Enantiomerically pure carboxylic acids are routinely obtained from N-acylsultams by Hydrogen Peroxide assisted saponification with Lithium Hydroxide in aqueous THF. 4 Alternatively, transesterification can be effected under neutral conditions in allyl alcohol containing Titanium Tetraisopropoxide, giving the corresponding allyl esters which can be isomerized/hydrolyzed with Wilkinson s catalyst (Chlorotris(triphenylphosphine)rhodium(I)) in Et0H-H20. This provides a convenient route to carboxylic acids containing base-sensitive functionality. Primary alcohols are obtained by treatment with L-Selectride (Lithium Tri-s-butylborohydride) in THF at ambient temperature. ... 

Alcohols and alkyl halides are classified as primary secondary or tertiary according to the degree of substitution of the carbon that bears the functional group (Section 2 13) Thus primary alcohols and primary alkyl halides are compounds of the type RCH2G (where G is the functional group) secondary alcohols and secondary alkyl halides are compounds of the type R2CHG and tertiary alcohols and tertiary alkyl halides are com pounds of the type R3CG... 

The reaction of aldoses with nitric acid leads to the formation of aldaric acids by oxidation of both the aldehyde and the terminal primary alcohol function to carboxylic acid groups Aldaric acids are also known as saccharic acids and are named by substi tutmg aric acid for the ose ending of the corresponding carbohydrate... 

Uronic acids are monosaccharides in which the terminal primary alcohol group is oxidized to a carboxyhc acid functional group, eg, D-glucuronic acid [6556-12-3] (11). 

Nickel peroxide is a solid, insoluble oxidant prepared by reaction of nickel (II) salts with hypochlorite or ozone in aqueous alkaline solution. This reagent when used in nonpolar medium is similar to, but more reactive than, activated manganese dioxide in selectively oxidizing allylic or acetylenic alcohols. It also reacts rapidly with amines, phenols, hydrazones and sulfides so that selective oxidation of allylic alcohols in the presence of these functionalities may not be possible. In basic media the oxidizing power of nickel peroxide is increased and saturated primary alcohols can be oxidized directly to carboxylic acids. In the presence of ammonia at —20°, primary allylic alcohols give amides while at elevated temperatures nitriles are formed. At elevated temperatures efficient cleavage of a-glycols, a-ketols... 

Because skin exhibits many of the properties of a lipid membrane, dermal penetration can often be enhanced by increasing a molecule s lipophilicity. Preparation of an ester of an alcohol is often used for this purpose since this stratagem simultaneously time covers a hydrophilic group and provides a hydrophobic moiety the ready cleavage of this function by the ubiquitous esterase enzymes assures availability of the parent drug molecule. Thus acylation of the primary alcohol in flucinolone (65) with propionyl chloride affords procinonide (66) the same transform... 

The homology between 22 and 21 is obviously very close. After lithium aluminum hydride reduction of the ethoxycarbonyl function in 22, oxidation of the resultant primary alcohol with PCC furnishes aldehyde 34. Subjection of 34 to sequential carbonyl addition, oxidation, and deprotection reactions then provides ketone 21 (31% overall yield from (—)-33). By virtue of its symmetry, the dextrorotatory monobenzyl ether, (/ )-(+)-33, can also be converted to compound 21, with the same absolute configuration as that derived from (S)-(-)-33, by using a synthetic route that differs only slightly from the one already described. 

With a secure route to pentacyclic amine 2, the completion of the total synthesis of 1 requires only a few functional group manipulations. When a solution of 2 in ethanol is exposed to Pd-C in an atmosphere of hydrogen, the isopropenyl double bond is saturated. When a small quantity of HCI is added to this mixture, the hydro-genolysis of the benzyl ether is accelerated dramatically, giving alcohol 15 in a yield of 96%. Oxidation of the primary alcohol in 15 with an excess of Jones reagent, followed by Fischer esterification, gives ( )-methyl homosecodaphniphyllate [( )-1] in an overall yield of 85 % from 2. 

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). 

A useful synthesis of allylstannanes from primary alcohols involves conversion of the alcohols into their O-substituted 5-methyl carbonodithioates, thermolysis to effect [3,3] rearrangement to the corresponding 5-substituted 5-methyl carbonodithioates, and treatment with a trialkyl-tin hydride under free-radical conditions to form the allylstannane21. This procedure has been applied to the synthesis of functionalized allylstannanes including (5)-( )-4-(benzyloxy)-2-pen-tenyl(tributyl)stannane22. 

Sulfonic esters are most frequently prepared by treatment of the corresponding halides with alcohols in the presence of a base. The method is much used for the conversion of alcohols to tosylates, brosylates, and similar sulfonic esters. Both R and R may be alkyl or aryl. The base is often pyridine, which functions as a nucleophilic catalyst, as in the similar alcoholysis of carboxylic acyl halides (10-21). Primary alcohols react the most rapidly, and it is often possible to sulfonate selectively a primary OH group in a molecule that also contains secondary or tertiary OH groups. The reaction with sulfonamides has been much less frequently used and is limited to N,N-disubstituted sulfonamides that is, R" may not be hydrogen. However, within these limits it is a useful reaction. The nucleophile in this case is actually R 0 . However, R" may be hydrogen (as well as alkyl) if the nucleophile is a phenol, so that the product is RS020Ar. Acidic catalysts are used in this case. Sulfonic acids have been converted directly to sulfonates by treatment with triethyl or trimethyl orthoformate HC(OR)3, without catalyst or solvent and with a trialkyl phosphite P(OR)3. ... 

The addition, therefore, follows Markovnikov s rule. Primary alcohols give better results than secondary, and tertiary alcohols are very inactive. This is a convenient method for the preparation of tertiary ethers by the use of a suitable alkene such as Me2C=CH2. Alcohols add intramolecularly to alkenes to generate cyclic ethers, often bearing a hydroxyl unit as well. This addition can be promoted by a palladium catalyst, with migration of the double bond in the final product. Rhenium compounds also facilitate this cyclization reaction to form functionalized tetrahydrofurans. 

In 2009, Tu et al. developed a novel iron-catalyzed C(sp )-C(sp ) bond-forming reaction between alcohols and olefins or tertiary alcohols through direct C(sp )-H functionalization. A series of primary alcohols were treated with alkenes or tertiary alcohols as their precursors, using the general catalysis system FeCls (0.15 equiv)/ 1,2-dichloroethane (DCE) (Scheme 36) [46]. 

We have developed an efficient and practical method for clean oxidation of starch (21-23) resulting in the oxidation of primary alcohol function in Ce position and the cleavage of vicinal diols in C2 and C3 position (Figure 30.2). We used small amounts of cheap iron tetrasulfophthalocyanine catalyst, pure water as reaction medium and H2O2 as clean oxidant to achieve a one-pot conversion of starch resulting in the introduction of aldehyde and carboxyl functions in polymer chains. The iron content... 

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