Synthesis unsaturated acetals

DL-cordycepose it was obtained in two steps, namely, epoxidation to 55 and mild, acid hydrolysis of the epoxide 55. For the synthesis of 53, substrate 54 was first brominated to the 2-bromo compound 57, which was dehydrobrominated with lithium amide, to afford the unsaturated acetal 58. cis-Hydroxylation of 58 under typical conditions then afforded 53. 

In contrast, the corresponding reactions of RCu/BFa reagents (R = phenyl or alkenyl) with allylic acetals obviously proceed in an anti 5n2 fashion, as shown in (67b). The unsaturated acetals (68), prepared from (R )-butane-1,2-diol, are opened by the PBu3-stabilized reagents to give, after hydrolysis, the (3-substituted aldehydes (69) with high ee (Scheme 27).68,69 The method has been applied to the preparation of a key intermediate (85% ee) for the synthesis of the California red scale pheromone.69... 

Both the enantiomers of Ipc2BH have been elegantly applied in the asymmetric hydroboration of safranol isoprenyl methyl ether for the synthesis of carotenoids (3R,3 R)-, (3S,3 S)-, and (3R,3 S meyo)-zeaxanthins (eq 5). (3,S,5/ ,3, S, 5 R)-Capsorubin, a carotenoid found in the red paprika Capsicum annuum, was synthesized via a key step involving asymmetric hydroboration of the unsaturated acetal followed by an aldol condensation (eq 6). ... 

Yamamoto and Maruoka investigated the reaction of chiral acetals with organoaluminum reagents. Unprecedented regio- and stereochemical control was observed in the addition of trialkylaluminums to chiral a,/3-unsaturated acetals derived from optically pure tartaric acid diamide [83]. The course of the reaction seemed to be highly influenced by the nature of substrates, solvents, and temperature. These findings provide easy access to optically active a-substituted aldehydes (84), /3-substituted aldehydes (85), a-substituted carboxylic acids (86), or allylic alcohols (87). Because optically pure RJi)- and (5,5)-tartaric acid diamides are both readily available, this method enables the predictable synthesis of both enantiomers of substituted aldehydes, carboxylic acids, and allylic alcohols from a,/3-unsaturated aldehydes (Sch. 54). 

Via stereoselective ethenolysis of 1,5-cyclooctadiene (COD), Bykov et al. [25] prepared l,d5-5,9-decatriene, a precursor for the synthesis of many ds-isomeric insect sex pheromone compounds. In the presence of the MoCl5/Si02/Me4Sn catalyst system, at 20 °C and an ethene pressure of 25 bar, a 80 % conversion of COD was obtained with a selectivity of 68.4% for l,ds-5,9-decatriene. From this triene, many long-chain (CiQ-Cig) unsaturated acetates, alcohols and aldehydes can be obtained with the required biologically active cis conformation. Cross-metathesis of cyclooctene with a-olefins in the presence of the same catalyst gave... 

Barrero et al. [81] carried out a more efficient synthesis of the keto acetate (31) from the unsaturated acetate (67), which they obtained earlier... 

When RU/AI2O3 prepared from acetylacetonate (sample G ) is used (Fig.2), selectivity to unsaturated alcohols remains low (15%) whereas citronellal become the main reaction product and the acetal is obtained in a negligible amount (< 1%). At higher conversions, 3,7-dimethyloctanol is formed by hydrogenation of citronellol. The preferential formation of citronellal on sample G and of acetal on sample F is likely to be related to the higher acidity of the catalyst prepared from RUCI3. It is in fact known that synthesis of acetals is catalyzed by an acidic medium. 

The stereospecific olefination method involving synthesis, separation, and base-catalysed, decomposition of diastereomeric P-hydroxyalkylphosphine oxides has been used for the preparation of pure isomers of y,S-unsaturated acetals (Scheme 11). The same principle has been extended to trisubstituted alkenes. The yields are generally still good, but the diastereomeric hydroxyphosphine oxides involved are less stable in some cases and the routes to them are less stereoselective. However, the method works reasonably well for the synthesis of ( )-and (Z)-allylic amines (Scheme 12). Unfortunately, (2-substituted-2-amino)-... 

Ethoxybutadienylboronate 88 was prepared from a,j3-unsaturated acetal 87, and used for synthesis of phenyl 1-propenyl ketone (89) by S-MC and hydrolysis [82]. Similarly the 2-acyl-l,4,5,6-tetrahydropyridine 91 was prepared by the coupling of 90 with an alkenyl triflate, which was derived from the corresponding lactam [83]. 

For the completion of the total synthesis from XXI-A it was necessary to preferentially attach the unsaturated acetic acid side chain to C-13 by a Reformatsky-type reaction and to maintain the base-unstable configuration at C-14. Compound XXIV, which has been obtained from XXI-A and from XXII-A through the equilibration of the ketals, was a very important intermediate since it is a monoketone and the methyl group adjacent to the keto function is held in an axial position by the equatorial hydroxy group at C-7. A Reformatsky reaction, followed by oxidation, dehydration, and hydrolysis afforded cassaic acid (XXXIV) identical with an authentic sample (12). Since cassaic acid had been converted to cassaine (XXXV) in 1939 by Faltis and Holzinger (2), this constituted a total synthesis and a final confirmation of structure of the parent alkaloid. 

The isolation of saturated and unsaturated acetic acid derivatives in the manganese(m) acetate oxidation of olefins has been reported earlier examples of this oxidation led solely to y-lactones. A one-step synthesis of aeo-di-carboxylic acid diesters has been reported, based on Kolbe electrolysis of oxalic and malonic half-esters in the presence of olefins, and is exemplified in Scheme 2. As part of a study of insect hormone activity, Kolbe electrolysis has been utilized in the preparation of aj9-unsaturated Cj4—Cj7 acid esters with a terminal quaternary alkyl group. The utility of liquid hydrogen fluoride in the Koch carbonylation of olefins has been descried, as has a general study of this reaction. ... 

Formylmethyltriphenylphosphorane (125) is a widely used Wittig reagent for the synthesis of ( )-aP-unsaturated aldehydes. Bestmann et al. have shown that, by the simple expedient of using the ethoxy-enol ether (126), aldehydes are converted into (Z)-aP-unsaturated acetals (127) and thus aldehydes (128). Laevulinic... 

In studies directed towards the synthesis of pseurotin A, the unsaturated acetal 3 has been used as a common starting material to prepare two different C-2-branched intermediates. In one route, 3 was 0-benzylated, the aldehyde im-masked with hydrochloric acid and oxidized to its carboxylic acid derivative. Esterification, dihydroxylation of the alkene then dimethylsulfoxide-thionyl chloride oxidation, addition of ethylmagnesium chloride and removal of the isopropylidene group gave compounds 4. In an alternative route, 3 was first epoxidized then treated sequentially with hydroxide, benzyl bromide-base and hydrochloric acid to give compounds 5. ... 

The synthesis of chiral piperidines has been accomplished through an intramolecular cyclization reaction using chiral phosphoric acid catalysts (Scheme 3.31) [29], Treatment of protected amines bearing tethered unsaturated acetals with catalytic amounts of a chiral phosphoric acid catalyzed the formation of chiral piperidines with high selectivity. 

Females of the California red scale (Aonidiella aurantii) release a mixture of the branched unsaturated acetates (332a) and (333) to attract males. Synthesis of the R,Z component (332a) was achieved by Roelofs et al. 74, 75) starting from (5 -(+)-carvone (321) (Scheme 59). The final product consisted of a mixture of the Z and E isomers, which were easily separable by GC. The absolute stereochemistry of the 3-methyl group in (333) is unknown. 

The reaction can be applied to the synthesis of q, /3-unsaturated esters and lactones by treatment of the ketene silyl acetal 551 with an allyl carbonate in boiling MeCN[356]. The preparation of the q,, 3-unsaturated lactone 552 by this method has been used in the total synthesis of lauthisan[357]. 

Acidic Cation-Exchange Resins. Brmnsted acid catalytic activity is responsible for the successful use of acidic cation-exchange resins, which are also soHd acids. Cation-exchange catalysts are used in esterification, acetal synthesis, ester alcoholysis, acetal alcoholysis, alcohol dehydration, ester hydrolysis, and sucrose inversion. The soHd acid type permits simplified procedures when high boiling and viscous compounds are involved because the catalyst can be separated from the products by simple filtration. Unsaturated acids and alcohols that can polymerise in the presence of proton acids can thus be esterified directiy and without polymerisation. 

Isophorone usually contains 2—5% of the isomer P-isophorone [471-01-2] (3,5,5-trimethyl-3-cyclohexen-l-one). The term a-isophorone is sometimes used ia referring to the a,P-unsaturated ketone, whereas P-isophorone connotes the unconjugated derivative. P-lsophorone (bp 186°C) is lower boiling than isophorone and can be converted to isophorone by distilling at reduced pressure ia the presence of -toluenesulfonic acid (188). Isophorone can be converted to P-isophorone by treatment with adipic acid (189) or H on(Ill) acetylacetoate (190). P-lsophorone can also be prepared from 4-bromoisophorone by reduction with chromous acetate (191). P-lsophorone can be used as an iatermediate ia the synthesis of carotenoids (192). 

The bromination of 4,5-j -dihydrocortisone acetate in buffered acetic acid does not proceed very cleanly (<70%) and, in an attempt to improve this step in the cortisone synthesis, Holysz ° investigated the use of dimethylformamide (DMF) as a solvent for bromination. Improved yields were obtained (although in retrospect the homogeneity and structural assignments of some products seem questionable.) It was also observed that the combination of certain metal halides, particularly lithium chloride and bromide in hot DMF was specially effective in dehydrobromination of 4-bromodihydrocortisone acetate. Other amide solvents such as dimethylacetamide (DMA) and A-formylpiperidine can be used in place of DMF. It became apparent later that this method of dehydrobromination is also prone to produce isomeric unsaturated ketones. When applied to 2,4-dibromo-3-ketones, a substantial amount of the A -isomer is formed. 

The azlactones of a-benzoylaminocinnamic acids have traditionally been prepared by the action of hippuric acid (1, Ri = Ph) and acetic anhydride upon aromatic aldehydes, usually in the presence of sodium acetate. The formation of the oxazolone (2) in Erlenmeyer-Plochl synthesis is supported by good evidence. The method is a way to important intermediate products used in the synthesis of a-amino acids, peptides and related compounds. The aldol condensation reaction of azlactones (2) with carbonyl compounds is often followed by hydrolysis to provide unsaturated a-acylamino acid (4). Reduction yields the corresponding amino acid (6), while drastic hydrolysis gives the a-0X0 acid (5). ... 

These thiazoles are of specific interest in that they display exceptional pharmacological properties. Additionally, the unsaturated 2-aminonitrile functionality of the above thiazoles is recognized for its versatile functionality and therefore for its ensuing significance in the synthesis of heterocycles. The synthetic utility of thiazoles 13a-f is illustrated by the reactions of the unsaturated 2-aminonitrile functionality in compounds 13b and 13c with formamidine acetate, resulting in the thiazolopyrimidines 14a and 14c respectively. The synthesis of this relatively rare family of heterocycles provides a route into structurally similar bioactive compounds. ... 

One of the most important routes to isoxazole and isoxazoline rings involving the formation of the 1—5 and 2—3 bonds involves the condensation of hydroxylamine with a,/8-unsaturated carbonyl compounds. This method was previously widely used, but it is now of no preparative value, though it has been recently applied to determine the configuration of oximes. " The only new modification of this synthesis is the use of the acetals (27) of a,/8-acetylenic aldehydes for preparation of 5-substituted isoxazoles (28)... 

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