Functional groups reductive conversions

Functional group inter-conversion of the end products can be accomplished through a straightforward sequence (Scheme 3.21). Treatment of cyclic substrate 17 under basic conditions affords the requisite hydroxy acid. Protection of the secondary alcohol as the silyl ether followed alkylation of the acid affords the methyl ester. Samarium mediated reduction and subsequent protection affords the orthogonally protected diol 19. 

Since (A) does not contain any other functional group in addition to the formyl group, one may predict that suitable reaction conditions could be found for all conversions into (A). Many other alternative target molecules can, of course, be formulated. The reduction of (H), for example, may require introduction of a protecting group, e.g. acetal formation. The industrial synthesis of (A) is based upon the oxidation of (E) since 3-methylbutanol (isoamyl alcohol) is a cheap distillation product from alcoholic fermentation ( fusel oils ). The second step of our simple antithetic analysis — systematic disconnection — will now be exemplified with all target molecules of the scheme above. For the sake of brevity we shall omit the syn-thons and indicate only the reagents and reaction conditions. 

Certain functional groups may be protected from reduction by conversion to anions that resist reduction. Such anions include the alkoxides of allylic and benzylic alcohols, phenoxide ions, mercaptide ions, acetylide ions, ketone carbanions, and carboxylate ions. Except for the carboxylate, phenoxide, and mercaptide ions, these anions are sufficiently basic to be proton-ated by an alcohol, so they are useful for protective purposes only in the... 

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

Azaloxan (12) is an antidepressant agent. Its synthesis can be accomplished starting with the reaction of catechol (7) and 3,4-dibromobutyronitrile (obtained by addition of bromine to the olefin) to give l,4-benzodioxan-2-ylacetonitrile (8). A series of functional group transformations ensues [hydrolysis to the acid (9), reduction to the alcohol (10) and conversion to a tosylate (11)] culminating in an SN-2 displacement reaction on tosylate 11 with l-(4-piperidinyl)-2-imidazolidi-none to give azaloxan (12) [3]. 

Oxidation is the conversion of a functional group in a molecule to a higher category reduction is conversion to a lower one. Conversions within a category are neither oxidations nor reductions. The numbers given at the bottom are only approximations. 

We discovered a complementary procedure for conversion of OMen to other functional groups. The ester P-OMen bond was shown to be cleaved in a stereoselective manner reductively [85,86]. The cleavage takes place with almost complete preservation of stereochemical integrity at phosphorus. The reducing agents are usually sodium or Hthium naphthalenide, lithium biphenyUde, and Hthium 4,4 -di-fert-butylbiphenyl (LDBB). The species produced is then quenched with an alkyl hahde or methanol to afford tertiary or secondary phosphines, respectively (Scheme 5b). Overall, the displacement reaction proceeds with retention of configuration. 

The stereocontrol and functional group tolerance exhibited by the palladium-catalyzed silane-mediated reductive enyne cyclization has led to its use as a key bond formation en route to structurally complex natural products. These include /3-necrodol,59 (—)-4a,5-dihydrostreptazolin,S9b ( )-laurene,S9c and, as illustrated by the conversion of 1,6-enyne 35a to furan 35b, ( )-phyllanthocin (Scheme 25).S9a... 

The review by Trewhella and Grint points out that a factor import in the ability of organic sulfur to enhance liquefaction is the reductive conversion of sulfur functional groups to H2S (. As the relative concentration of H2S increases, improvements are observed in both liquefaction rates and conversions (25). 

The most popular reducing agent for conversion of aromatic nitro compounds to amines is iron [166]. It is cheap and gives good to excellent yields [165, 582]. The reductions are usually carried out in aqueous or aqueous alcoholic media and require only catalytic amounts of acids (acetic, hydrochloric) or salts such as sodium chloride, ferrous sulfate or, better still, ferric chloride [165]. Thus the reductions are run essentially in neutral media. The rates of the reductions and sometimes even the yields can be increased by using iron in the form of small particles [165]. Iron is also suitable for reduction of complex nitro derivatives since it does not attack many functional groups [555]. 

Reduction of p-ketoesters in aqueous ethanolic sulphuric acid leads to removal of both functional groups and the formation of a hydrocarbon. This reaction which was discovered in 1907 [117] and recognised in 1912 [118] as involving a skeletal rearrangement is now termed the Tafel rearrangement. Conversions of the type 26 into 27 occur in 30 - 60 % yields [118,119] and the hydrocarbon is easily separated... 

The importance of aromatic nitro compounds arises in particular from the ready conversion of the nitro group into other functional groups, principally by routes involving initial reduction to the amino group. The following procedures, of which the first is by far the most important, are available for the synthesis of aromatic nitro compounds. 

Similarly, with the same type of photocatalyst (Pt/TiC>2 or Fe2C>3) the decomposition of levulinic (4-oxopentanoic) acid in oxygen-free aqueous solution has been investigated in detail (60). In addition to the decarboxylation reaction, oxidative C-C scissions led to propionic and acetic acids (further converted into methane and ethane) and reductive cleavages to acetone and ethanal. The formation of acetone was apparently favoured by higher Pt contents (however product distributions referred to equal illumination durations and not to equal conversions). It was suggested that the variety of products resulted from the presence of two functional groups in levulinic acid. The quantum yield was probably of the order of 5 x IQ-3. 

---