Aldehydes unbranched

The intensity of the m/z 31 ion is sufficient to suggest the presence of oxygen. Masses 44 and 57 are usually present, and an M - 18 peak is also detectable. Mass 44 usually suggests an aldehyde unbranched on the a-carbon, but this ion is also prominent in the mass spectra of cyclobutanol, cyclopentanol, cyclohexanol, and so forth. Mass 57 (C3H5O) is also fairly intense for C5 and larger cyclic alcohols. If an aldehyde is present, M - 1, M - 18, and M - 28 peaks are observed. 

The reactions also led to high regioselectivity (> 20 1). For alkylated aldehydes unbranched in the a-position, however, low diastereoselectivity (d.r. 1.7 1) and yields of 38% were obtained, although enantioselectivity remained excellent (> 97% ee). Use of aromatic substrates resulted in a d.r. of 1 1 to 1.5 1 only, and the enantioselectivity was in the range 67 to 80% ee [93]. Some representative examples of the L-proline-catalyzed aldol reaction with hydroxyacetone are given in Scheme 6.35. 

The complex 8, formed by the addition of 2-propenylmagnesium chloride to 7, adds to aromatic aldehydes, 1-alkanals, a-branched and unbranched alkanals uniformly from the 7 c-face leading to hoinoallylic alcohols with 88-94% ee35 (Method A). After hydrolytic workup, both components can be recycled. Allyl complexes 10, generated from 9, prefer 67-attack and lead to the ent-homoallylic alcohols with excellent enantioselectivity36 (Method B) (Table 8). 

The formation of isomeric aldehydes is caused by cobalt organic intermediates, which are formed by the reaction of the olefin with the cobalt carbonyl catalyst. These cobalt organic compounds isomerize rapidly into a mixture of isomer position cobalt organic compounds. The primary cobalt organic compound, carrying a terminal fixed metal atom, is thermodynamically more stable than the isomeric internal secondary cobalt organic compounds. Due to the less steric hindrance of the terminal isomers their further reaction in the catalytic cycle is favored. Therefore in the hydroformylation of an olefin the unbranched aldehyde is the main reaction product, independent of the position of the double bond in the olefinic educt ( contrathermodynamic olefin isomerization) [49]. 

The allenic stannanes react with aldehydes under the influence of Lewis acids such as BF3 and MgBr2. Unbranched aldehydes are not very stereoselective, but branched aldehydes show a strong preference for the syn adduct. 

The combination of Ni(COD)2/NHC complexes with EtaSiH as the reducing agent has also proved to be effective in inter molecular couplings of aldehydes and alkynes (Scheme 9) [21]. A broad range of substrates underwent couplings, including aromatic, non-aromatic, and terminal alkynes as well as branched, unbranched, and aromatic aldehydes. The regioselectivity with... 

Propargylic mesylates show only modest diastereoselectivity in Pd(0)/lnl-mediat-ed additions to unbranched and conjugated aldehydes [118]. However, the presence of a terminal trimethylsilyl substituent on the alkynyl grouping greatly improves the diastereoselectivity of such additions (Table 9.55) [119]. 

At present, most enamine-catalyzed aldol reactions are reliable only with electron-poor aromatic aldehyde acceptors, hi addition, a handful of aliphatic aldehydes (e.g. isobutyraldehyde or pivalaldehyde) are often used as acceptors. The use of unbranched aldehyde acceptors is difficult, and generally only modest yields have been obtained. In addition, unsaturated aldehydes are curiously absent from the list of commonly used acceptors. On a positive side, it should be noted that even potentially racemizing a-chiral aldehydes have been employed as acceptors. As an example, in the recent synthesis of caUipeltoside C, MacMillan and coworkers were able to employ protected Roche aldehyde 113 as a starting material (Scheme 22) [204]. 

The present method is practical and efficient as it employs readily available enantioenriched propargylic alcohols as precursors to the allenylindium reagents. With achiral aldehydes the diastereoselectivity is high for branched aldehydes, moderate for unbranched aldehydes, and low for benzaldehyde (Table I). With cHral a-methyl aldehydes the additions proceed under effective reagent control to afford anti adducts of high ee and with excellent diastereoselectivity (eq. 1 and 2). Comparable results were obtained with 3 1 dimethyl sulfoxide-tetrahydrofuran (DMSO-THF) as the solvent. 

While cyclohexanecarbaldehyde and pivaldehyde, being a-branched aldehydes, are excellent substrates for most ligands leading to nearly perfect enantioselec-tion, unbranched aldehydes still remain cumbersome substrates. 

Over the last five years, we have designed, synthesized, and applied new ligands for asymmetric 1,2- and 1,4-addition reactions. Suitable ligands were found for the addition of alkyl-, aryl-, and alkenylzinc reagents to a,(3-unsaturated aldehydes and ketones, a-branched and unbranched aliphatic aldehydes, and imines. Although some substrates such as ketones and other carbonyl compounds have remained a challenge, we believe that this system provides an excellent entry into various classes of chiral intermediates. Application of these synthesized complex molecules is the current pursuit in our laboratories. 

Later work by Barbot and Miginiac2 and Jones and Knochel3 showed that additions of allylic zinc reagents to aldehydes are also reversible and occur by S/,-2 pathways. In the former case, the mixture of regioisomeric alcohol adducts from prenylzinc bromide and 3-pentanone changed composition in favor of the unbranched isomer with increased reaction times and temperature (equation 4)2. 

The SCLPs are defined as unbranched, aliphatic chains containing between nine and 18 carbon atoms, with up to three double bonds in the carbon backbone, and ending in an alcohol, aldehyde, or acetate functional group (Figure 12.5) [42]. Laboratory studies have demonstrated that there is no acute, subchronic, chronic, or developmental mammalian toxicity even with exposure to high doses of SCLPs or chemically similar compounds [39, 43]. 

The t2 period includes the cool flame reaction, which may be followed by a period of decreased reaction velocity, and leads up to autoignition. Lewis and von Elbe (108, 110) believe that in the r2 region unbranched chains are initiated by reaction of formaldehyde and perhaps other aldehydes with oxygen. Second-stage ignition is not believed to be of the branched-chain type but occurs as a result of unbalancing of thermal equilibrium. 

When there is a branch at C-3 in an aldose, the aldehydo form is hydrated to a much lesser extent than in an unbranched sugar the branching causes a 1,3-parallel interaction with one of the hydroxyl groups of the gem-diol. Whereas the ratio of aldehydrol to aldehyde is 10 1 for threose and 5 1 for erythrose, it is only 1.7 1 and 1.5 1, respectively, for their 3-C-methyl derivatives, and 0.4 1 for 3,3-dimethyl-DL-g/ym-o-tetrose.13... 

When the enthalpies of reaction between branched ketones and the corresponding 1,1-disubstituted alkenes are calculated using the multiple enthalpies of formation available for the latter, the following ranges are obtained Me/i-Pr, 196.6 to 200.5 Et/i-Pr, 201.2 to 206.6 and Me/t-Bu, 200.5 to 205.1 kJmol-1. Perhaps it is reasonable to conclude that the reaction enthalpies for the branched compounds either will be approximately constant, as for the unbranched ketone/alkene conversions, or will be more endothermic with branching, as in the branched aldehyde/alkene conversions. In either case, the least endothermic reaction enthalpy for the Me/i-Pr conversion above seems inconsistent and therefore the enthalpies of formation for 2,3-dimethyl-l-butene from References 16 or 26, which are essentially identical, should be selected. These enthalpies were also selected in a previous section. However, there is too much inconstancy, as well as too much uncertainty, in the replacement reactions of carbonyls and olefins to be more definitive in our conclusions. 

An important feature of this reaction is that in contrast to most other catalytic asymmetric Mannich reactions, a-unbranched aldehydes are efficient electrophiles in the proline-catalyzed reaction. In addition, with hydroxy acetone as a donor, the corresponding syn-l, 2-aminoalcohols are furnished with high chemo-, regio-, diastereo-, and enantioselectivities. The produced ketones 14 can be further converted to 4-substituted 2-oxazolidinones 17 and /i-aminoalcohol derivatives 18 in a straightforward manner via Baeyer-Villiger oxidation (Scheme 9.4) [5]. 

The Stacker reaction has been employed on an industrial scale for the synthesis of racemic a-amino acids, and asymmetric variants are known. However, most of the reported catalytic asymmetric Stacker-type reactions are indirect and utilize preformed imines, usually prepared from aromatic aldehydes [24]. A review highlights the most important developments in this area [25]. Kobayashi and coworkers [26] discovered an efficient and highly enantioselective direct catalytic asymmetric Stacker reaction of aldehydes, amines, and hydrogen cyanide using a chiral zirconium catalyst prepared from 2 equivalents of Zr(Ot-Bu)4, 2 equivalents of (R)-6,6 -dibromo-1, l -bi-2-naphthol, (R)-6-Br-BINOL], 1 equivalent of (R)-3,3 -dibromo-l,l -bi-2-naphthol, [(R)-3-Br-BINOL, and 3 equivalents of N-methylimida-zole (Scheme 9.17). This protocol is effective for aromatic aldehydes as well as branched and unbranched aliphatic aldehydes. 

When the reaction is carried out with a ketone the product is known as a ketal. With low molecular weight unbranched aldehydes and ketones the equilibrium lies to the right. If it is desired to make acetals or ketals of higher molecular weight molecules, the removal of water is necessary to drive the equilibrium to the right (23). 

Trost has exploited the asymmetric alkynylation of an a-unbranched acetaldehyde in an elegant synthesis of the core of the mitomycin analog FR900482 [22]. This is a remarkable example wherein an enolizable aldehyde participates in the addition reaction. It has been suggested that this is critical for the success of these substrates, because the aldehyde undergoes reversible enolization. (Eq. 18). 

McDonald performed an asymmetric synthesis of D-desosamine, with high selectivity, by diastereoselective addition of TMS-acetylene to an a-unbranched aldehyde obtaining the propargylic alcohol [23]. The reaction proceeded in nearly 100 % diastereoselectivity albeit in moderate (60 %) yield (Eq. 19). 

For satisfactory diemo- and stereoselectivity, most catalytic, direct cross-aldol methods are limited to the use of non enolizable (aromatic, a-tert-alkyl) or kineti-cally non enolizable (highly branched, ,/funsaturated) aldehydes as acceptor carbonyls. With aromatic aldehydes, however, enantioselectivity is sometimes moderate, and the dehydration side-product may be important. With regard to the donor counterpart, the best suited pronucleophile substrates for these reactions are symmetric ketones (acetone) and ketones with only one site amenable for enolization (acetophenones). With symmetric cyclic or acyclic ketones superior to acetone, syn/anti mixtures of variable composition are obtained [8b, 11, 19a]. Of particularly broad scope is the reaction of N-propionylthiazolidinethiones with aldehydes, which regularly gives high enantioselectivity of the syn aldol adduct of aromatic, a,fi-unsaturated, branched, and unbranched aldehydes [13]. 

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