Acyclic aldehyde

Chart I. Trivial names (with recommended three-letter abbreviations in parentheses) and structures (in the aldehydic, acyclic form) of the aldoses with three to six carbon atoms. Only the D-forms are shown the L-forms are the mirror images. The chains of chiral atoms delineated in bold face correspond to the configurational prefixes given in italics below the names... 

Excellent enantioselectivities up to complete asymmetric induction are achieved in the preparation of a-alkylated aldehydes, acyclic and cyclic ketones via (-)-(S)- and (+ )-(7 )-1 -amino-2-methoxymethylpyrrolidine (SAMP/RAMP-hydrazones) (see Section 1.1.1.4.2.). Due to the unique mechanism of metalation and alkylation, the absolute configuration of the final products can be predicted. Since both antipodes of the auxiliary are available, either enantiomer of the desired alkylated carbonyl compound can be prepared... 

Meyer and coworkers125 have reported the condensation reaction between conjugated 1,1-enediamines and aldehydes. Acyclic 1,1-enediamines 160 react with aldehydes in a 2 1 ratio to give 2,6-diamino-4,5-dihydropyridine-3,5-dicarboxylates (161) with elimination of water and amine (equation 59). 

Fortunately, the use of lithiated hydrazones derived from (S)- or ( )-l-amino-2-methoxymethylpyiro-lidine (SAMP or RAMP) as nucleophiles for asymmetric alkylations have provided a solution to the problems described above with metallated acyclic ketimines and aldimines. Lithiated SAMP or RAMP hydrazones of cyclic ketones are also alkylated in high yields. A major advantage of these chiral hydrazones is that their derivatives of aldehydes, acyclic and cyclic ketones all yield mainly ( )cc-. (Z)cN-Iithiated species on deprotonation with LDA in ethereal solvents under kinetic control. The ( )cc-configuration obtains as a result of the minimization of steric interactions in the usual closed transition... 

Enolates with Chiral Auxiliaries. Enantioselective alkylation of carbonyl derivatives encompassing chiral auxiliaries constitutes an important synthetic process. The anions derived from aldehydes, acyclic ketones, and cyclic ketones with (S)-l-Amino-2-methoxymethylpyrrolidine (SAMP) are used to obtain alkylated products in good to excellent yields and high enan-tioselectivity (e.g. eq 21). ... 

There are various chemical components present in plant-origin antimicrobials including, saponin and flavonoids, thiosulflnates and glucosinulates. EOs may contain different components including terpenoids, sesquiterpenes and possibly diter-penes with different groups of aliphatic hydrocarbons, acids, alcohols, aldehydes, acyclic esters or lactones. 

In general it may be stated that ease of formation of dioxolans and other acetals and ketals is rou ly in the order aldehydes > acyclic ketones and cyclohexanones > cyclopentanones > o , 3-unsaturated ketones > a-mono- and di-substituted ketones > aromatic ketones, though variations in this order may be experienced as a result of additional steric or electronic factors. Use of this general principle, and judicious choice of experimental conditions, generally makes possible selective dioxolan formation in polycarbonyl compounds this subject has been extensively reviewed in the steroid field (Ref. l,pp. 3-17). 

Information on a given oxygenate reviewed in this work is listed under the functional group of that compound that is, formaldehyde is listed under aldehydes, acyclic formic acid is under acids, monobasic, etc. The order of listing under a given family of compounds is in increasing... 

Aldehydes. When the group —C(=0)H, usually written —CHO, is attached to carbon at one (or both) end(s) of a linear acyclic chain the name is formed by adding the suffix -al (or -dial) to the name of the hydrocarbon containing the same number of carbon atoms. Examples are butanal for CHjCHjCHjCHO and propanedial for, OHCCH CHO. 

When the aldehyde group is directly attached to a carbon atom of a ring system, the suffix -carbaldehyde is added to the name of the ring system, e.g., 2-naphthalenecarbaldehyde. When the aldehyde group is separated from the ring by a chain of carbon atoms, the compound is named (1) as a derivative of the acyclic system or (2) by conjunctive nomenclature, for example, (1) (2-naphthyl)propionaldehyde or (2) 2-naphthalenepropionaldehyde. 

The aldol reactions of enamines may be formally considered to proceed via acyclic amino aldehyde or amino ketone forms, in spite of the fact that the cyclic enamine forms can also take part in aldol reactions. 

Thus the reactions of cyclic or acyclic enamines with acrylic esters or acrylonitrile can be directed to the exclusive formation of monoalkylated ketones (3,294-301). The corresponding enolate anion alkylations lead preferentially to di- or higher-alkylation products. However, by proper choice of reaction conditions, enamines can also be used for the preferential formation of higher alkylation products, if these are desired. Such reactions are valuable in the a substitution of aldehydes, which undergo self-condensation in base-catalyzed reactions (117,118). Monoalkylation products are favored in nonhydroxylic solvents such as benzene or dioxane, whereas dialkylation products can be obtained in hydroxylic solvents such as methanol. The difference in products can be ascribed to the differing fates of an initially formed zwitterionic intermediate. Collapse to a cyclobutane takes place in a nonprotonic solvent, whereas protonation on the newly introduced substitutent and deprotonation of the imonium salt, in alcohol, leads to a new enamine available for further substitution. 

Occasionally it happens that the oxo compound, produced by oxidation, forms a hydrate which is further oxidized to a dihydroxy compound. Attention must be given to the possibility (so far unreported) that when the hydrated species is in equilibrium with a trace of the ring-opened structure a sufficiently fast oxidation rate of the amino-aldehyde (i.e. the acyclic structure) could lead to the incorrect conclusion that the original material was not cyclic. 

Most studies in this field have been on nitrones. One of the reasons for this is probably because nitrones are readily available compounds that can be obtained from aldehydes, amines, imines, and oximes [2, 11]. Moreover, most acyclic ni-... 

In fact, it has been found (52) that in unbuffered solution, at room temperature, authentic 2-deoxy ribose 5-phosphate reduces more than 4 molar equivalents of periodate, but. that there is no noticeable slowing down of the reaction rate after the reduction of the first molar equivalent. This may be owing to the fact that only the aldehydo form (76) of 2-deoxy ribose 5-phosphate has a free vicinal diol group as the acyclic 2-deoxy ribitol 5-phosphate reduces one molar equivalent of periodate quite fast (58), it is probable that the time-curve of periodate uptake by the phosphorylated sugar reflects the rate of formation of the aldehyde form from the furanose form. 

The synthetic challenge is now reduced to the preparation of intermediates 2-4. Although intermediates 3 and 4 could potentially be derived in short order from very simple precursors (see Scheme 4), intermediate 2 is rather complex, particularly with respect to stereochemistry. Through a short sequence of conventional functional group manipulations, it is conceivable that aldehyde 2 could be derived from intermediate 9. Hydrolysis and keta-lization reactions could then permit the formation of 9 from intermediate 11, the cyclic hemiaminal of the highly stereo-defined acyclic molecule, intermediate 12. 

Arai and co-workers have used chiral ammonium salts 89 and 90 (Scheme 1.25) derived from cinchona alkaloids as phase-transfer catalysts for asymmetric Dar-zens reactions (Table 1.12). They obtained moderate enantioselectivities for the addition of cyclic 92 (Entries 4—6) [43] and acyclic 91 (Entries 1-3) chloroketones [44] to a range of alkyl and aromatic aldehydes [45] and also obtained moderate selectivities on treatment of chlorosulfone 93 with aromatic aldehydes (Entries 7-9) [46, 47]. Treatment of chlorosulfone 93 with ketones resulted in low enantioselectivities. 

Addition of the metalated civ-epoxysilane to acyclic or cyclic ketones generally proceeded with higher diastereoselectivity than the addition to aldehydes. A low diastcreomeric ratio (60 40) was only observed upon addition to 4-methylcyclohexanone13. 

In contrast to the 2-butenylboranes, 2-butcnylboronates have found widespread application in acyclic diastereoselective synthesis owing to their ease of preparation (Section 1.3.3.3.3.1.1.), configurational stability and highly stereoselective reactions with aldehydes3 4. The results of reactions of substituted allylboronates and representative achiral aldehydes are summarized in Table 1. 

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