Nitriles, olefinic, reduction

The diversity associated with silyl protecting groups as well as the chemical conditions available for their removal makes them attractive alternatives to benzyl protection of the hydroxy groups of either D- or L-tartaric acid derivatives. O-isopropylidene-L-threitol (37) is mono-protected with er -butyldimethylsilyl chloride to furnish 266, which is converted in three steps to the nitrile 267. Reduction with DIBAL and Wittig olefination followed by desilylation with fluoride and Swern oxidation of the resulting alcohol provides aldehyde 268, which reacts with methyl 10-(triphenylphosphorane)-9-oxo-decanoate (269) to afford enone 270. Reduction of 270 with subsequent preparative TLC and acetal hydrolysis furnishes (9R)-271 and (9 S)-272, both interesting unsaturated trihydroxy Cig fatty acid metabolites isolated from vegetables [91] (Scheme 62). 

In addition to the nitrile and alcohol routes for fatty amine preparation, processes have been described by Unocal and Pennwalt Corporation, using an olefin and secondary amine (14—16) by Texaco Inc., hydrogenation of nitroparaffins (17—20) by Onyx Corporation, reaction of an alkyl haUde with secondary amines (21,22) by Henkel Cie, GmbH, reduction of an ester in the presence of a secondary amine (23) by catalytic hydroammonolysis of carboxyhc acids (24) and by the Hofmann rearrangement (25). 

One development involves the use of vitamin B 2 to cataly2e chemical, in addition to biochemical processes. Vitamin B 2 derivatives and B 2 model compounds (41,42) cataly2e the electrochemical reduction of alkyl haUdes and formation of C—C bonds (43,44), as well as the 2inc—acetic acid-promoted reduction of nitriles (45), alpha, beta-unsaturated nitriles (46), alpha, beta-unsaturated carbonyl derivatives and esters (47,48), and olefins (49). It is assumed that these reactions proceed through intermediates containing a Co—C bond which is then reductively cleaved. 

ATBN - amine terminated nitrile rubber X - Flory Huggins interaction parameter CPE - carboxylated polyethylene d - width at half height of the copolymer profile given by Kuhn statistical segment length DMAE - dimethyl amino ethanol r - interfacial tension reduction d - particle size reduction DSC - differential scanning calorimetry EMA - ethylene methyl acrylate copolymer ENR - epoxidized natural rubber EOR - ethylene olefin rubber EPDM - ethylene propylene diene monomer EPM - ethylene propylene monomer rubber EPR - ethylene propylene rubber EPR-g-SA - succinic anhydride grafted ethylene propylene rubber... 

The key intermediate 25 was prepared efficiently from aldehyde 23, obtained by reduction of nitrile 22 with Dibal-H. Treatment of 23 with the lithium salt of frans-diethyl cinnamylphosphonate furnishes compound 24 in 75 % yield and with a 20 1 ratio of E Z olefin stereoisomers. The stage is now set for the final and crucial operations to complete the molecular skeletons of endiandric acids A and B. 

Although the biosynthetic cascade hypothesis predicts the co-occurrence of endiandric acids D (4) and A (1) in nature, the former compound was not isolated until after its total synthesis was completed in the laboratory (see Scheme 6). Our journey to endiandric acid D (4) commences with the desilylation of key intermediate 22 to give alcohol 31 in 95% yield. The endo side chain is then converted to a methyl ester by hydrolysis of the nitrile to the corresponding acid with basic hydrogen peroxide, followed by esterification with diazomethane to afford intermediate 32 in 92% overall yield. The exo side chain is then constructed by sequential bromination, cyanide displacement, ester hydrolysis (33), reduction, and olefination (4) in a straight-... 

Intramolecular nitrile oxide—olefin cycloaddition of oxazolidine and thiazoli-dine oximes 407 (R = H, Me R1 =H, Me X = 0, S n = 1,2) proceed stereose-lectively, yielding tricyclic fused pyrrolidines and piperidines. Thus, 407 (n =2 R = H R1 =Me X=S) has been oxidized to the nitrile oxides with sodium hypochlorite, in the presence of triethylamine in methylene chloride, to give the isoxazolothiazolopyridine 408 in 68% yield. Reduction of 408 with lithium aluminum hydride affords mercaptomethylmethylpiperidine 409 in 24% yield (448). 

Diastereoselective intermolecular nitrile oxide—olefin cycloaddition has been used in an enantioselective synthesis of the C(7)-C(24) segment 433 of the 24-membered natural lactone, macrolactin A 434 (471, 472). Two (carbonyl)iron moieties are instrumental for the stereoselective preparation of the C(8)-C(ii) E,Z-diene and the C(i5) and C(24) sp3 stereocenters. Also it is important to note that the (carbonyl)iron complexation serves to protect the C(8)-C(ii) and C(i6)-C(i9) diene groups during the reductive hydrolysis of an isoxazoline ring. 

In the cathodic reduction of activated olefins, chlorosilanes also act as trapping agents of anionic intermediates. Nishiguchi and coworkers described the electrochemical reduction of a,/ -unsaturated esters, nitriles, and ketones in the presence of Me3SiCl using a reactive metal anode (Mg, Zn, Al) in an undivided cell to afford the silylated compounds [78]. This reaction provides a valuable method for the introduction of a silyl group into activated olefins. 

Chromium(II) sulfate is a versatile reagent for the mild reduction of a variety of bonds. Thus aqueous dimethylformamide solutions of this reagent at room temperature couple benzylic halides, reduce aliphatic monohalides to alkanes, convert vicinal dihalides to olefins, convert geminal halides to carben-oids, reduce acetylenes to /raw5-olefins, and reduce a,j3-unsatu-rated esters, acids, and nitriles to the corresponding saturated derivatives. These conditions also reduce aldehydes to alcohols. The reduction of diethyl fumarate described in this preparation illustrates the mildness of the reaction conditions for the reduction of acetylenes and o ,j8-unsaturated esters, acids, and nitriles. 

Aliphatic nitro compounds are versatile building blocks and intermediates in organic synthesis,14 15 cf. the overview given in the Organic Syntheses preparation of nitroacetaldehyde diethyl acetal.16 For example, Henry and Michael additions, respectively, lead to 1,2- and 1,4-difunctionalized derivatives.14 18 1,3-Difunctional compounds, such as amino alcohols or aldols are accessible from primary nitroalkanes by dehydration/1,3-dipolar nitrile oxide cycloaddition with olefins (Mukaiyama reaction),19 followed by ring cleavage of intermediate isoxazolines by reduction or reduction/hydrolysis.20 21... 

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