Reduction of the Aromatic Moiety

APPLY the skill 18.21 Using toluene as your only source of carbon atoms, show how you would prepare the following compound. 

22 Starting with isopropyl benzene, propose a synthesis for acetophenone. (Hint. Make sure to count the number of carbon atoms in the starting material and product.) 

Recall from earlier in this chapter that under forcing conditions benzene will react with three equivalents of molecular hydrogen to produce cyclohexane. 

With some catalysts and under certain conditions, it is possible to selectively hydrogenate a vinyl group in the presence of an aromatic ring. 

The vinyl group is reduced, but the aromatic moiety is not. Nonce that AH for this reaction is only shghdy lower than what we expect for a double bond (—120 kJ/mol), which can be attributed to the fact that the double bond is conjugated in this case. 

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The reduction of the aromatic moieties with NaBH4-RhCl3 in ethanol ... 

An isoindol1 none moiety forms part of the aromatic moiety of yet another antiinflammatory propionic acid derivative. Carboxylation of the anion from -nitro-ethylbenzene (45) leads directly to the propionic acid (46). Reduction of the nitro group followed by condensation of the resulting aniline (47) with phthalic anhydride affords the corresponding phthalimide (48). Treatment of that intermediate with zinc in acetic acid interestingly results in reduction of only one of the carbonyl groups to afford the isoindolone. There is thus obtained indoprofen (49). ... 

Dibenzobicyclo[2.2.2]octadienones (34) bearing an aromatic substituent were designed to probe the unsynunetrization of the carbonyl it orbital arising from the aromatic % orbitals [103,104], Reduction of the carbonyl moiety of 2- (R H) and 3-substituted (R3 H) dibenzobicyclo[2.2.2]octadienones (34) was studied by using sodium borohydride in methanol at - 3 °C. The 2- (34a) and 3-nitrodibenzo-bicyclo[2.2.2]octadienones (34d)... 

Reduction of the aromatic nucleus in AjjV-dimethylbenza-mide occurs by an initial single electron transfer to give a radical anion. Protonation of the radical anion generates a radical and a second electron transfer gives the amide enolate 1. Protonation of the cross-conjugated trienolate moiety in 1 occurs carbonyl group to give the cyclohexa-1,4-diene 2. ... 

Palladium-catalyzed a-arylation of ketones is performed with arylene dihalides and bifunctional aromatic ketones 148 to result in the bond formation at the r/) -a-carbon of the ketone, leading to polyketone 149. The reaction is carried out in the presence of Pd(0) and various phosphines. Several bidentate phosphines and bulky alkylphosphines such as dppf, BINAP, PCys, and P Bu3 are shown to be effective, while PPh3 results in no reaction. Arylene dibromide and diiodide are applicable as the co-monomers. The polymerization reaction is carried out in THE in the presence of NaO Bu at 75 °C under N2, and polymers 149 are isolated in 60-80% yields (M = 7000-15 000). Polyketone 149 is further transformed to conjugated polymer PPV by reduction of the ketone moiety with LiAlH4 followed by dehydration with an acid (Equation (69)). 

The association of the xanthate-based tetralone synthesis with the alkyla-tive Birch reduction and other reactions allowing the modification of the aromatic core constitutes a particularly potent combination. This is illustrated by the expedient synthesis of tricyclic system 65 pictured in the top part of Scheme 36 (Cordero-Vargas et al, personal communication). Routes to highly complex architectures can be conceived through modification of the olefinic partner, the substitution pattern of the aromatic moiety, or the nature of the alkylating agent associated with the Birch reduction. 

Similar studies, however, suggest that N-nitrosobutalin will be quite persistent in soils (Oliver and Konston, 1978). Reduction of N-nitrosopendimethalin has been observed in anaerobic soils (Smith et al., 1979). Product studies indicate, however, that the nitroso moiety remains intact and reduction of the aromatic nitro group in the 6-position occurs to give the aromatic amine (Equation 3.36). 

Having obtained the desired cis stereochemistry, the alcohol was oxidized to the aldehyde with pyridinium chlorochromate and subjected to Wolff-Kishner reduction to yield the CDE moiety in overall yield of 30% from the unsaturated tricylic ester. Lithium-ammonia reduction of the aromatic nucleus gave the 3,7 enone 206. 

The initial discovery route to analogs of crizotinib is shown in Scheme 1, and was designed to vary the nature of the aromatic moiety at a late stage in the synthesis. Initial borohydride reduction of the acetophenone generates the racemic alcohol, which is coupled to 3-hydroxy-2-nitropyridine through a Mitsunobu reaction. Nitro reduction followed by bromination introduces the halogen to the 5-position. Boc protection of the amino function enables Pd-mediated borylation to be employed to introduce the... 

A two-enzyme process to obtain alcohols from carboxylic adds was reported by Ni et al. as shown in Scheme 6.32. The reduction of the add moiety was demonstrated by the hyperthermophile Pyrococcus furiosus using 5 bar of hydrogen as re-ductant. It was also shown that no reaction occurred in the absence of P. furiosus or hydrogen. Both aromatic and aliphatic substrates were used and reduction of the carboxylic add resulted in the accumulation of aldehyde intermediate. The aldehyde was reduced using a CRED with overall yields of 11-99% [47]. 

A variety of natural products and pharmaceutical agents contain a tetrahydroquinoline moiety [31]. Recently, a simple and general access to these heterocycles by a so-far unknown domino reaction of aromatic nitro compounds 7-65 and 2,3-dihydrofuran mediated by indium in water has been described by Li and coworkers (Scheme 7.19) [32]. It is assumed that the process is initiated by reduction of the nitro group in 7-65 to give the aniline 7-66 on treatment with indium in... 

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