Syntheses zinc reduction

This cleavage reaction is more often seen in structural analysis than in synthesis The substitution pattern around a dou ble bond is revealed by identifying the carbonyl containing compounds that make up the product Hydrolysis of the ozonide intermediate in the presence of zinc (reductive workup) permits aide hyde products to be isolated without further oxidation... 

Lie and coworkers31 reported the synthesis and NMR properties of all geometrical isomers of conjugated linoleic acids. Pure geometric isomers of conjugated linoleic acid (CLA) were prepared from castor oil as the primary starting material. Methyl octadeca-9Z, 11 /i-dienoate (36) and methyl octadeca-9Z,llZ-dienoate (38) were obtained by zinc reduction of methyl santalbate (35, methyl octadec-11 -en-9-ynoatc) and methyl... 

In fact, the sensitive disubstituted alkene of 14 turned out to not be stable to the subsequent A1C1, coupling conditions, so the alkene and the secondary alcohol were protected together as the bromoether 15. Condensation of the derived enol ether 16 with the sulfone 2 in the presence of DTBMP (2,6-di-/-butyl-4-methylpyridine) then gave 17. Yamaguchi lactonization followed by regeneration of the alkene by zinc reduction completed the synthesis of 1. 

Zinc reduction of chalcogenopyrylium ions has found application in synthesis. In order to prepare 4,4 -bithiopyrylium dication [13 (Z = S, R = H)], thiopyrylium (2) is first reacted with excess zinc in acetonitrile at 0°C under a nitrogen atmosphere, and then with triphenylmethyl fluoro-borate, iodide, or perchlorate to give the corresponding bithiopyrylium salt (71TL3999). According to the authors the reaction occurs as shown in Scheme 17. 

Preparation of the Auxiliary. A synthesis of the (1/ ) auxiliary has been reported starting from (-i-)-camphor (eq 1). Zinc reduction of the intermediate imine (2) followed by sulfonylation and ketone reduction with Ca(B 114)2 afforded the cis.endo product in 70-75% overall yield from camphorquinone (1). 

Due to the relatively high stability of the N-2,2,2-trichloroethoxycarbonyl (Troc) group to acids and its selective removal by zinc reduction even in the presence of Al-benzyloxy-carbonyl derivatives, it can offer interesting possibilities in the syntheses of particular pep-tidic compounds for example, it has been used for N -protection of lysine in the synthesis of The Af -Troc-protected lysine is readily prepared by reaction of the copper(II) complex with 2,2,2-trichloroethyl chloroformate (Troc-Cl)h d or by reaction of Z-Lys-OH (obtained via the benzylidene route, see Section 2.1.2.2.1.3) with 2,2,2-trichloroethyl chlor-oformate.f ... 

Thus it has been used as the first stage to obtain the starting material for the microbiological method with CSD-10 and simplified in more recent work leading to a synthesis of estrone in four steps from 3p-acetoxy-19-hydroxyandrost-5-en-17-one (ref. 116). Cholesteryl acetate was transformed by standard methods to the required androstane compound shown in the following scheme, which with hypobromous acid followed by lead tetraacetate and zinc reduction (cf. ref. 115) afforded the 19-hydroxy derivative. This with thallium nitrate in dioxan underwent loss of formaldehyde and hydration with water to afford the 19-nor-10p-alcohol in 70% yield. The diol obtained by saponification was converted by Oppenauer oxidation with N-methylpiperid-4-one as hydride aceptor (ref. 117) and afforded a 78% yield of the enone which was transformed almost quantitatively into... 

The synthesis of 3-benzoyl-A-homo-3-aza-5) -androstan-16-one (37), an analogue of the alkaloid samanine (36) from Salamandra maculosa, has been reported. Sodium borohydride reduction of the known compound (38) followed by tosylation alTorded the tosylate (39) the nitrile group was reduced by diborane and cyclized by benzoic anhydride-pyridine to the derivative (40a) similar cyclization with acetic anhydride-pyridine yielded the related acetamide (40b). This cyclization requires one equivalent of anhydride and the uncyclized amide is not an intermediate in the reaction. Jones oxidation of (40a) was followed by conversion into a benzylidene ketone derivative (41) with benzaldehyde-KOH in methanol. Reduction of (41) with sodium borohydride and acetylation furnished (42). Treatment of compound (42) with ozone followed by mild zinc reduction produced an acetoxy-ketone, which was further reduced by Zn-HBr-CH2Cl2 to the ketone (37). 

Although this route enabled the first stereocontrolled synthesis of 7a-unsubstituted 1-oxacephems, it could not supply the compound quickly enough because of difficulty in handling the aluminium amalgam for the reduction and the magnesium metal for the Grignard reaction and due to the poor reproducibility of the zinc reduction. 

As alluded to earlier, the reductive cyclization of nitro ketones often leads to A-hydroxyindoles when the intermediate reduction prodnct, a hydroxylamine, undergoes cyclization. This path can be made dominant if desired. Thus, as shown in Scheme 12, several researchers have developed such a methodology. Acheson may have been the first chemist to achieve this reaction. A two-phase zinc reduction of o-nitrophenylacetaldehyde yields the unstable N-hydroxyindole, which was trapped as the more stable (distillable) A-acetoxyindole (equation 1) [85]. Wong and colleagues use a lead-promoted reductive cyclization approach to Al-hydroxyindoles in excellent yields (equation 2 and 34-37) [86]. Wojciechowski s team employed a VNS synthesis of the A-hydroxyindole precursors (equation 3) [87]. 

Stereoselective synthesis of highly functionalized azatricycles (e.g., 75) has been achieved by copper-catalysed Henry reaction of enals with nitromethane, zinc reduction of the nitro group and subsequent tosylation, followed by iodocyclization. The iodine is easily removed afterwards by hydrogenation, or can be used to introduce other functionality, such as by epoxidation of the adjacent alcohol. 

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