Nonanal, reduction

The procedure described is a modification of the directions of Prelog, Frenkiel, Kobelt, and Barman. Cyclodecanone has been prepared by the dehydration of sebacoin followed by catalytic hydrogenation, by the pyrolysis of the thorium or yttrium salt of nonane-1,9-dicarboxylie acid, and by the ring enlargement of cyclononanone, as well as by the reduction of sebacoin. ... 

Bicyclo[3.3.1]nonan-9-one is another ketone that exhibits interesting stereoselectivity. Reduction by hydride donors is preferentially syn to electron-attracting substituents at C-5 (X = EWG in the structure shown below) and anti to electron-releasing substituents (X = ERG below). These effects are observed even for differentially substituted phenyl... 

Spirapril (37) is a clinically active antihypertensive agent closely related structurally and mechanistically to enalapril. Various syntheses are reported with the synthesis of the substituted proline portion being the key to the methods. This is prepared fkim l-carbobenzyloxy-4-oxopro-line methyl ester (33) by reaction with ethanedithiol and catalytic tosic acid. The product (34) is deprotected with 20% HBr to methyl l,4-dithia-7-azospiro[4.4 nonane-8-carboxylate (35), Condensation of this with N-carbobenzyloxy-L-alanyl-N-hydroxysuccinate leads to the dipeptide ester which is deblocked to 36 by hydrolysis with NaOH and then treatment with 20% HBr. The conclusion of the synthesis of spirapril (37) follows with the standard reductive alkylation [11]. 

Hydrogenolysis of cxo-2-phenyl-9-oxabicyclo[3.3, l]nonan-2-ol proceeds exclusively with retention over Raney nickel and with inversion over palladium. No reduction with palladium occurred at all until a drop of perchloric acid was added (36). 

Although dichloroborane has been successfully used to reduce dialkyl sulphoxides, it was less useful for the reduction of diaryl sulphoxides and recent work26 has found that fully substituted bromoboranes can fill this gap. Three reagents were introduced, viz. bromodimethylborane, 9-bromo-9-borabicyclo[3.3.1]nonane (9-BBN-Br) and tribromo-borane, the reactions being shown in equation (5) ... 

Enantioselective reduction is not possible for aldehydes, since the products are primary alcohols in which the reduced carbon is not chiral, but deuterated aldehydes RCDO give a chiral product, and these have been reduced enantioselectively with B-(3-pinanyl)-9-borabicyclo[3.3.1]nonane (Alpine-Borane) with almost complete optical purity. ... 

Transannular interactions lead to ring closures and reductions to adamantane compounds when dienes of the bicyclo[3.3.1]nonane family are treated with Brpnsted acids and triethylsilane. Compounds 48-51 form reaction mixtures containing various amounts of products 52-54 (R = OH, O2CCF3, Cl) under such conditions.243 The best yields of hydrocarbon 52 occur when the dienes are treated with a 25% excess of sulfuric acid and a 50% excess of triethylsilane in dichloromethane at 20°.243 The stereospecific nature of these transannular reductions is demonstrated by the observation that the enantiomeric purity of the chiral diene 55 is retained in the chiral hydrocarbon product 56 (Eq. 98).243 Dienes of... 

Benzyltriethylammonium tetrathiomolybdate, [BnNEt3]2MoS4, is a useful sulfur transfer reagent which has now been shown to effect a one-pot, three-step sequence of S-transfer— reduction—Michael addition. The intramolecular version successfully produces 1,4-oxathianes from the bromoenone 108 (Scheme 65). In like manner, the bicyclo[3.3.1]nonane skeleton incorporating a thiopyran ring can be constructed . 

In comparison with the hydroboration and diborafion reactions, thioboration reactions are relatively limited. In 1993, Suzuki and co-workers reported the Pd(0)-catalyzed addition of 9-(alkylthio)-9-BBN (BBN = borabicyclo [3.3.1] nonane) derivatives to terminal alkynes to produce (alkylthio)boranes, which are known as versatile reagents to introduce alkylthio groups into organic molecules [21], Experimental results indicate that the thioboration reactions, specific to terminal alkynes, are preferentially catalyzed by Pd(0) complexes, e.g. Pd(PPh3)4, producing (thioboryl)alkene products, in which the Z-isomers are dominant. A mechanism proposed by Suzuki and co-workers for the reactions involves an oxidative addition of the B-S bond to the Pd(0) complex, the insertion of an alkyne into the Pd-B or Pd-S bond, and the reductive elimination of the (thioboryl)alkene product. 

The mercuration-demercuration reaction of cw,cw-l,5-cyclooctadiene (3) has been widely studied in order to get some insight into the synthesis of 9-oxa and 9-azabicyclo-nonane derivatives. However, the results of the reaction have often been the subject of some controversy since the ratio of the two isomeric bicyclo[3.3.1]- [199 and 201] and [4.2.1]- [198 and 200] nonanes, after reduction (equation 166), strongly depended on the reaction conditions of the mercuration step168,169. 

The synthetic sequence, which shows only the succesful solutions adopted in every step, is outlined in Scheme 13.1.11. Reaction of l Chloroadamantan-4-one (39) [15] with sodium-potassium alloy in ether gave a mixture of ketonic and hydroxylated material which upon oxidation with Jones reagent gave 7-methylenebicyclo[3.3.1]nonan-2-one (40) in 75% yield. Reduction of 40 with sodium borohydride gave the alcohol 41 which could be also obtained in better yields from l-chloroadamantan-4-one with a large excess of sodium-potassium... 

Asymmetric reduction of ketones using Alpine-borane . Alpine-borane = B-isopinocampheyl-9-borabicyclo[3.3.1]nonane. 

Baum and Archibald reported the synthesis of 2,2,6,6-tetranitrobicyclo[3.3.1]nonane (142). This synthesis starts from the dioxime (140), which on halogenation with chlorine, followed by oxidation with hypochlorite and reductive dehalogenation with hydrogen in the presence of palladium on carbon, yields 2,6-dinitrobicyclo[3.3.1]nonane (141). Oxidative nitration of (141) with sodium nitrite and silver nitrate under alkaline conditions yields 2,2,6,6-tetranitrobi-cyclo[3.3.1]nonane (142). The greater molecular freedom in 2,2,6,6-tetranitrobicyclo[3.3.1] nonane (crystal density-1.45 g/cm ) compared to the isomeric 2,2,6,6-tetranitroadamantane (crystal density-1.75 g/cm ) is reflected is their considerably different crystal densities. 

Complex hydrides can be used for the selective reduction of the carbonyl group although some of them, especially lithium aluminum hydride, may reduce the a, -conjugated double bond as well. Crotonaldehyde was converted to crotyl alcohol by reduction with lithium aluminum hydride [55], magnesium aluminum hydride [577], lithium borohydride [750], sodium boro-hydride [751], sodium trimethoxyborohydride [99], diphenylstarmane [114] and 9-borabicyclo[3,3,l]nonane [764]. A dependable way to convert a, -un-saturated aldehydes to unsaturated alcohols is the Meerwein-Ponndorf reduction [765]. 

Chemical reduction of aromatic aldehydes to alcohols was accomplished with lithium aluminum hydride [5i], alane [770], lithium borohydride [750], sodium borohydride [757], sodium trimethoxyborohydride [99], tetrabutylam-monium borohydride [777], tetrabutylammonium cyanoborohydride [757], B-3-pinanyl-9-borabicyclo[3.3.1]nonane [709], tributylstannane [756], diphenylstan-nane [114], sodium dithionite [262], isopropyl alcohol [755], formaldehyde (crossed Cannizzaro reaction) [i7i] and others. 

Reduction of unsaturated ketones to unsaturated alcohols is best carried out Nit v complex hydrides. a,/3-Unsaturated ketones may suifer reduction even at the conjugated double bond [764, 879]. Usually only the carbonyl group is reduced, especially if the inverse technique is applied. Such reductions are accomplished in high yields with lithium aluminum hydride [879, 880, 881, 882], with lithium trimethoxyaluminum hydride [764], with alane [879], with diisobutylalane [883], with lithium butylborohydride [884], with sodium boro-hydride [75/], with sodium cyanoborohydride [780, 885] with 9-borabicyclo [3.3.1]nonane (9-BBN) [764] and with isopropyl alcohol and aluminum isopro-... 

Reduction of a, -acetylenic ketones with chiral borane NB-Enanthrane prepared by addition of 9-borabicyclo[3.3.1]nonane to the benzyl ether of nopol yielded optically active acetylenic alcohols in 74-84% yields and 91-96% enantiomeric excess [770]. Another way to optically active acetylenic alcohols is reduction with a reagent prepared from lithium aluminum hydride and (2S, 3R)-( -I- )-4-dimethylamino-3-methy 1-1,2-dipheny 1-2-butanol. At —78° mainly R alcohols were obtained in 62-99% yield and 34-90% enantiomeric excesses [893]. 

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