Aldehydes, a- synthesis

Optically active a-kytbvxy aldehydes. A synthesis of chiral a-hydroxy aldehydes involves reaction of 1 with methyl hydroxymethoxyacetate to form the methoxycarbonyl aminal 2. The product is treated with a Grignard reagent in the presence of MgCl2 to form the keto aminal 3. A second Grignard reaction with 3 forms an intermediate (a), which is hydrolyzed to 1 and an a-hydroxy aldehyde (4) ... 

Bednarski, M, Danishefsky, S, Interactivity of chiral catalysts and chiral auxiliaries in the cycloaddition of activated dienes with aldehydes a synthesis of L-glucose, J. Am. Chem. Soc., 108, 7060-7067, 1986. 

An ale. soln. of the startg. m. added to an ale. soln. of K-tetraearbonylhydrido-ferrate, and stirred 5 hrs. at room temp, under argon furfurylaeetone. Y 82%. — This is the 2nd step of a 2-step proeess for the prepn. of methyl ketones from aldehydes, a synthesis with addition of 3 C-atoms. F. e. s. M. Yamashita et al., Tetrah. Let. 1975, 1867. 

Most substrates, with the exception of hydroxypymvate, have a threo configuration of hydroxyl groups at the C-3 and C-4 positions (139). The new stereocenter formed in TK-catalyzed addition is formed in the threo configuration with high diastereo-selectivity (151). Using TK-catalyzed condensations of hydroxypymvic acid with a number of aldehydes a practical preparative synthesis of L-idose [5934-56-5], L-gulose [6027-89-0], 2-deoxy-L-xylohexose, and... 

In a synthesis of decinine a phenol was protected as a methanesulfonate that was stable during an Ullman coupling reaction and during condensation, catalyzed by calcium hydroxide, of an amine with an aldehyde. Aryl methanesulfonates are cleaved by warm sodium hydroxide solution. " ... 

In general, imines are too reactive to be used to protect carbonyl groups. In a synthesis of juncusol, however, a bromo- and an iodocyclohexylimine of two identical aromatic aldehydes were coupled by an Ullman coupling reaction modi-fied by Ziegler. The imines were cleaved by acidic hydrolysis (aq. oxalic acid, THF, 20°, 1 h, 95% yield). Imines of aromatic aldehydes have also been prepared... 

Aldehyde 198 served as a key intermediate in a synthesis of the alkaloid ajmaline. The. Mannich aminomethylation transform triggers disconnection of two bonds in 198 to form dialdehyde 199, which by connective transform application can be converted to cyclopentene 200.58,59 The reduction in functional group reactivity and in structural complexity are both apparent by comparison of 198 and 200. 

The Kiliani-Fischer synthesis proceeds by nucleophilic addition of HCN to an aldose, followed by conversion of the cyano group to an aldehyde. A mixture of stereoisomers results the two aldoses are epi-meric at C-2. Section 25.20 describes the modern version of the Kiliani-Fischer synthesis. 

In a German patent issued in 1929, Bergs described a synthesis of some 5-substituted hydantoins by treatment of aldehydes or ketones (1) with potassium cyanide, ammonium carbonate, and carbon dioxide under several atmospheres of pressure at 80°C. In 1934, Bucherer et al. isolated a hydantoin derivative as a by-product in their preparation of cyanohydrin from cyclohexanone. They subsequently discovered that hydantoins could also be formed from the reaction of cyanohydrins (e.g. 3) and ammonium carbonate at room temperature or 60-70°C either in water or in benzene. The use of carbon dioxide under pressure was not necessary for the reaction to take place. Bucherer and Lieb later found that the reaction proceeded in 50% aqueous ethanol in excellent yields for ketones and good yields for aldehydes. ... 

A sulfanilamide drug of prolonged action, 2-p-aminobenzenesulfamido-4-methylpyiimidine (sulfomerazine 162), first prepared by Japanese chemists from acetacetic aldehyde in 82% yield (49JPJ447), ranks among practically valuable 2-amino-4-methylpyrimidine derivatives. Later, a synthesis of this product directly from l-methoxybut-l-en-3-yne (100°C, AcONa, AcOH, 3 h) in 64% yield has been developed (76MI1). 

A synthesis of 2-alkyl-2,3-dihydro-y-pyrones (187) from methoxybutenyne and aldehydes has been described (83TL4551). The condensation of lithiomethoxy-butenyne (184) with aldehydes at -78°C leads to the secondary alcohols 185, which form the dihydropyrones 187 via hydration of the acetylenic bond and hydrolysis of the methoxyethenyl group to the ketoenol 186 (0°C, p-TSA, THF, H2O or 30% HCIO4, 20 min) folowed by intramolecular cycloaddition. 

C ( propyl) N phenylmtrone to N phenylmaleimide, 46, 96 semicarbazide hydrochloride to ami noacetone hydiochlonde, 46,1 tetraphenylcyclopentadienone to diphenyl acetylene, 46, 44 Alcohols, synthesis of equatorial, 47, 19 Aldehydes, aromatic, synthesis of, 47, 1 /3-chloro a,0 unsaturated, from ke tones and dimethylformamide-phosphorus oxy chloride, 46, 20 from alky 1 halides, 47, 97 from oxidation of alcohols with dimethyl sulfoxide, dicyclohexyl carbodumide, and pyndimum tnfluoroacetate, 47, 27 Alkylation, of 2 carbomethoxycyclo pentanone with benzyl chloride 45,7... 

An analogous solvent effect was observed upon treatment of the chiral a-alkoxy aldehyde 11 with 2-lithio-4-methylfuran in the presence of zinc bromide. This highly diastereoselective addition reaction was the key step in a synthesis of the enantiomcrically pure C-10-C-20 fragment of the immunosuppressant KK 506139. 

Besides simple alkyl-substituted sulfoxides, (a-chloroalkyl)sulfoxides have been used as reagents for diastereoselective addition reactions. Thus, a synthesis of enantiomerically pure 2-hydroxy carboxylates is based on the addition of (-)-l-[(l-chlorobutyl)sulfinyl]-4-methyl-benzene (10) to aldehydes433. The sulfoxide, optically pure with respect to the sulfoxide chirality but a mixture of diastereomers with respect to the a-sulfinyl carbon, can be readily deprotonated at — 55 °C. Subsequent addition to aldehydes afforded a mixture of the diastereomers 11A and 11B. Although the diastereoselectivity of the addition reaction is very low, the diastereomers are easily separated by flash chromatography. Thermal elimination of the sulfinyl group in refluxing xylene cleanly afforded the vinyl chlorides 12 A/12B in high chemical yield as a mixture of E- and Z-isomers. After ozonolysis in ethanol, followed by reductive workup, enantiomerically pure ethyl a-hydroxycarboxylates were obtained. 

In a synthesis of maytansinoids, a 10 1 ratio of adducts results from the reaction of ethyl lithiodithioacetate with the enantiomerically pure aldehyde ( + )-(2S, 3S, 4S)-3,4-epoxy-2,4-dimethyl-5-trimethylsilyloxypentanal°. 

A synthesis of aldehydes developed by Meyers begins with the commercially available dihydro-1,3-oxazine derivatives 132 (A = H, Ph, or COOEt). Though the ions (133) prepared from 132 are ambident, they are regioselectively alkylated at... 

With a-monosubstituted ylides the oxidation results in the formation of alkenes (by subsequent Wittig reaction on the intermediate aldehyde). A recent example of such synthesis is found in the preparation of all-(Z)-cyclododecate-traene by oxidation of the appropriate bis-ylide [33]. It must be pointed out that an approach of the same macrocycle based on ring closing metathesis was found ineffective. 

Example Optically active aldehyde (10) was needed for a synthesis of biotin. The compound has a 1,1-dlX disconnection (10a) clearly available and a C-N (amide) disconnection leaving (11) which has the same skeleton as the amino acid cysteine (12). 

Suggest a synthesis for the perfumery compound strawberry aldehyde (21) - not of course an aldehyde at all. 

As an extension of this work, the same authors explored such methodology for the synthesis of 2,6-disubstituted dihydropyrans using secondary homopropargylic alcohols (Scheme 10, route E). Surprisingly, the treatment of pent-4-yn-2-ol and 3-methylbutanal in the presence of FeCls led to unsaturated ( )-(3-hydroxyketone and ( )-a,p-unsaturated ketone in 2.5 1 ratio and 65% yield, without any trace of the expected Prins-type cyclic product (Scheme 22) [36]. To test the anion influence in this coupling, FeCE and FeBrs were used in a comparative study for the reaction of pent-4-yn-2-ol (R = R" = H, = Me) and several aldehydes. A range of aldehydes except for benzaldehyde was transformed into unsaturated (3-hydroxy-ketones in moderate to good yields. 

The phosphonate (176) has been used for the addition to aldehydes of a masked jS-keto-ester function and applied in the synthesis of ( )-7(f),9(t)-trisporic acid B methyl ester. The isomerically pure phosphonate (177) has been used in a synthesis of dehydro-Cig juvenile hormone," the anion being generated by treatment with lithium di-isopro-pylamide in THF-HMPT at - 65 °C for 1 min. 

Entries 10 to 14 show reactions involving acetals. Interestingly, Entry 10 shows much-reduced stereoselectivity compared to the corresponding reaction of the aldehyde (The BF3-catalyzed reaction of the aldehyde is reported to be 24 1 in favor of the anti product ref. 80, p. 91). There are no stereochemical issues in Entries 11 or 12. Entry 13, involving two cyclic reactants, gave a 2 1 mixture of stereoisomers. Entry Mis a step in a synthesis directed toward the taxane group of diterpenes. Four stereoisomeric products were produced, including the Z E isomers at the new enone double bond. 

Trialkylsilyl groups have a modest stabilizing effect on adjacent carbanions (see Part A, Section 3.4.2). Reaction of the carbanions with carbonyl compounds gives (3-hydroxyalkylsilanes. (3-Hydroxyalkylsilanes are converted to alkenes by either acid or base.270 These eliminations provide the basis for a synthesis of alkenes. The reaction is sometimes called the Peterson reaction.211 For example, the Grignard reagent derived from chloromethyltrimethylsilane adds to an aldehyde or ketone and the intermediate can be converted to a terminal alkene by acid or base.272... 

The camphor sultam derivative 21A was used in a synthesis of epothilone. The stereoselectivity of the aldol addition was examined with several different aldehydes. Discuss the factors that lead to the variable stereoselectivity in the three cases shown. 

S )-3-nydroxy-2-mcthylpropanoic acid, 13-A, can be obtained in enantiomeri-cally pure form from isobutyric acid by a microbiological oxidation. The aldehyde 13-B is available from a natural product, pulegone, also in enantiomerically pure form. Devise a synthesis of enantiomerically pure 13-C, a compound of interest as a starting material for the synthesis of a-tocopherol (vitamin E). 

There are several procedures for synthesis of terminal alkenyl stannanes that involve addition to aldehydes. A well-established three-step sequence culminates in a radical addition to a terminal alkyne.150... 

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