Reduction sequence

The synthesis of butylbenzene illustrates the acylation-reduction sequence... 

The two step acylation-reduction sequence is required Acylation of benzene puts the side chain on the ring with the correct carbon skeleton Clemmensen reduc tion converts the carbonyl group to a methylene group... 

Acylation. Acylation is the most rehable means of introducing a 3-substituent on the indole ring. Because 3-acyl substituents can be easily reduced to 3-aLkyl groups, a two-step acylation—reduction sequence is often an attractive alternative to direct 3-aLkylation. Several kinds of conditions have been employed for acylation. Very reactive acyl haUdes, such as oxalyl chloride, can effect substitution directiy without any catalyst. Normal acid chlorides are usually allowed to react with the magnesium (15) or 2inc (16) salts. The Vilsmeier-Haack conditions involving an amide and phosphoms oxychloride, in which a chloroiminium ion is the active electrophile, frequentiy give excellent yields of 3-acylindoles. 

Industrial Synthetic Improvements. One significant modification of the Stembach process is the result of work by Sumitomo chemists in 1975, in which the optical resolution—reduction sequence is replaced with a more efficient asymmetric conversion of the meso-cyc. 02Lcid (13) to the optically pure i7-lactone (17) (Fig. 3) (25). The cycloacid is reacted with the optically active dihydroxyamine [2964-48-9] (23) to quantitatively yield the chiral imide [85317-83-5] (24). Diastereoselective reduction of the pro-R-carbonyl using sodium borohydride affords the optically pure hydroxyamide [85317-84-6] (25) after recrystaUization. Acid hydrolysis of the amide then yields the desired i7-lactone (17). A similar approach uses chiral alcohols to form diastereomic half-esters stereoselectivity. These are reduced and direedy converted to i7-lactone (26). In both approaches, the desired diastereomeric half-amide or half-ester is formed in excess, thus avoiding the cosdy resolution step required in the Stembach synthesis. 

The Nenitzescu process is presumed to involve an internal oxidation-reduction sequence. Since electron transfer processes, characterized by deep burgundy colored reaction mixtures, may be an important mechanistic aspect, the outcome should be sensitive to the reaction medium. Many solvents have been employed in the Nenitzescu reaction including acetone, methanol, ethanol, benzene, methylene chloride, chloroform, and ethylene chloride however, acetic acid and nitromethane are the most effective solvents for the process. The utility of acetic acid is likely the result of its ability to isomerize the olefinic intermediate (9) to the isomeric (10) capable of providing 5-hydroxyindole derivatives. The reaction of benzoquinone 4 with ethyl 3-aminocinnamate 35 illustrates this effect. ... 

Low -molecular-weight ozonides are explosive and are theretore not isolated. Instead, the ozonide is immediately treated with a reducing agent such as zinc metal in acetic acid to convert it to carbonyl compounds. The net result of the ozonolysis/reduction sequence is that the C=C bond is cleaved and oxygen becomes doubly bonded to each of the original alkene carbons. If an alkene with a letrasubstituted double bond is ozonized, two ketone fragments result if an alkene with a trisubstituted double bond is ozonized, one ketone and one aldehyde result and so on. 

A similar Evans asymmetric aldol/reduction sequence could also serve well in a synthesis of fragment 158. Compounds 161 and 162 thus emerge as potential precursors to 158. In theory, building blocks 161 and 162 could be procured in optically active form from commercially available and enantiomerically pure (+)-/ -citro-nellene (163) and D-mannitol (164), respectively (see Scheme 42). 

High levels of diastereocontrol in an ISOC reaction were induced by a stereogenic carbon center that bears a Si substituent (Scheme 23) [55]. For instance, conversion of nitro alkenes (e.g., 199) to j3-siloxyketones (e.g., 203) has been accomplished via a key ISOC reaction-reduction sequence with complete control of 1,5-relative stereochemistry. The generality of the ISOC reaction of a silyl nitronate with a vinylsilane was demonstrated with seven other examples. Corresponding INOC reaction proceeded with lower stereoselectivity. 

Organometallic Addition/Reduction Sequence on Chiral o -Aminonitriles... 

Deracemization via the biocatalytic stereoinversion is usually achieved by employing whole cells. In the case of secondary alcohols, it is believed that microbial stereoinversion occurs by an oxidation-reduction sequence... 

Pure chromium metal is made by a two-step reduction sequence. First, sodium dichromate is reduced to chromium(III) oxide by heating in the presence of charcoal ... 

Reductive bleaches are generally less costly than oxidative bleaches but tend to give a greenish white compared with the reddish white tones from peroxide. Combining the two in an oxidation/reduction sequence gives a more neutral white, this being known as a full... 

Scheme 1.49. Cationic domino rearrangement/reduction sequence of a-hydroxy epoxides.

The Michael addition/Meerwein-Ponndorf-Verley (MPV) reduction sequence developed by Node and coworkers is another easily implementable strategy for the... 

The transformation of the cyano group could also introduce a new chiral center under diastereoselective control (Figure 5.13). Grignard-transimination-reduction sequences have been employed in a synthesis of heterocyclic analogues of ephedrine [81]. The preferential formation of erythro-/3-amino alcohols may be explained by preferential hydride attack on the less-hindered face of the intermediate imine [82], and hydrocyanation of the imine would also appear to proceed via the same type of transition state. In the case of a,/3-unsaturated systems, reduction- transimination-reduction may be followed by protection of the /3-amino alcohol to an oxazolidinone, ozonolysis with oxidative workup, and alkali hydrolysis to give a-hydroxy-/3-amino acids [83]. This method has been successfully employed in the synthesis L-threo-sphingosine [84]. 

Ene-nitrile oxidoisoquinolinium betaine 131 was readily prepared from vinyl triflate aldehyde 79 (Scheme 1.14). Palladium-catalyzed cyanation of vinyl triflate 79 with Zn(CN)2 in DMF at 60 °C produced ene-nitrile aldehyde 129 in 85 % yield [54]. Using the previously developed Staudinger-aza-Wittig reduction sequence, aldehyde 129 was coupled with cyclic ketal azide 121 to afford a 79 % yield of amine 130. The cyclic ketal amine 130 was then treated with 9 1 mixture of CH2CI2/TFA to provide ene-nitrile oxidoisoquinolinium betaine 131 in 93 % yield. 

For a similar enolization-reduction sequence, see Lovchik MA, Goeke A, Frater G (2007) J Org Chem 72 2427... 

Sodium cyanoborohydfide reaction with 1 entails the intermediacy of a thermally unstable n1-hydroxymethyl complex CpFe(CO)2(CH2OH) (4). When the reduction sequence was carried out in ethanol at room temperature, only trace amounts of... 

The synthesis of Ir4(CO)i2 is similar to that of Rh4(CO)j2, except that, in this case, the reactions can be carried out not only under high pressure (350 atm) but also at high temperatures (100—200°)u4. An infrared study, under pressure (100 atm, 100°) using copper bronze as halide acceptor249, indicates a reduction sequence of the following type ... 

The efficiency of the [2 + 2]-cycloadditions of 417 was utilized in a strategy for the synthesis of cephalosporin derivatives that carry an acetone or acetic acid ester group in the 3-position (Scheme 6.88) [175]. Liberated in the presence of 2-(trimethylsilyl-oxy)propene, 417 underwent cycloaddition leading to 435, treatment of which with tetrabutylammonium or hydrogen fluoride furnished the A3-cephalosporin 436 admixed with the A2-isomer. This mixture was converted to pure 436 by an oxidation-reduction sequence. In addition to the trimethylsilylenol ether of acetone, the... 

All the three polypyridyl complexes display the reversible reduction sequence 2 + / + /0. The relative potential values are reported in Table 7. As far as the nature of such redox changes is concerned, it is important to recall the ambiguity that exists in attributing metal-centred or ligand-centred redox processes for metal-polypyridine complexes. 

Figure 87, which refers to [Coni(Me2[14]py-dieneN4)(MeCN)2]3 +, shows that, as expected, these complexes display the gradual reduction sequence CoIII II/I 0, with features of electrochemical quasireversibility (E3/4-E1/4 slightly higher than 56.4). 

Though the rearrangements of the reactants 10c delivered single regioiso-mers, the products 12c (R=nBu/R =H) were isolated as a mixture of diastereo-mers after the rearrangement reduction sequence. Likewise, the 3,3-sigma-... 

In a related study, the oxidation-reduction sequence was carried out in the presence of an olefin (Scheme 21). Two products were formed. The major product resulted from the net reduction of the carboxylic acid to an aldehyde. The minor product resulted from trapping of the radical anion intermediate generated from the reduction reaction by the olefin. It should be noted that, in the absence of a trapping group, the acid can be selectively reduced to the aldehyde without any over-reduction. Although not in the scope of this review, this is a very useful transformation in its own right [35]. At this time, the yields of the cyclized products from the cyclization reaction of the radical anion with the olefin remain low. 

Although not yet optimized for C-C bond formation, these reactions demonstrated the potential for using mixed anodic oxidation - cathodic reduction sequences for initiating transformations that would be difficult to accomplish using more conventional chemical routes. It is hard to imagine putting a strong... 

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