Propionaldehydes 3-substituted

The glycidic esters are of interest primarily because upon hydrolysis aud decarboxylation they aflFord aldehydes (if ClCHjCOOEt is used) or ketones (if substituted chloroacetic esters- ClCHRCOOEt are employed) having a higher carbon content than the original aldehyde or ketone. Thus (I) gives o-phenyl-propionaldehyde or hydratropaldehyde (II) ... 

Hetero-substituted r)3-allyltitanocenes have also been studied. Functionalized q3-allyltita-nium complexes (X = SiMe3, OPh, SPh) have been prepared by transmetallation of Cp2TiCl with the corresponding allyllithiums, and were found to react regiospecifically with propionaldehyde to give functionalized homoallylic alcohols 11 (Scheme 13.14) [25]. 

Reaction of various aldehydes with hydrogen sulfide leads to substituted thiophenes, dihydrothiophenes, dithiolanes and trithiolane, as well as to six-membered ring thiopyran derivatives and dithiins. Ledl (33) obtained 2,4-dimethylthiophene (1, R Me) as a product of the reaction of propionaldehyde with hydrogen sulfide in the presence of ammonia. Sultan (29) reported the formation of 2,4-diethylthiophene (1, R - Et), 2,4-dibutyl-thiophene (1, R - Bu), and their dehydro derivatives from the reaction of ammonium sulfide with butyraldehyde and caproaldehyde (hexanal), respectively. The mechanism suggested for their formation is depicted in Scheme 1. Space limitations do not allow us to discuss the mechanism here in detail (for additional information, see ref. 29). 

Similarly, with acetaldehyde and propionaldehyde as the starting materials, one gets the 2,4-dimethyl-6-ethyl- and 2-ethy 1-4,6-dimethyl derivatives (33,37), In the presence of acetaldehyde, the higher aldehydes give various substituted... 

Chakrabarti and coworkers at Eli Lilly in the United Kingdom have reported the initial discovery and synthesis of olanzapine (Schemes 5 and,6). The thiophene 22 was synthesized by adding a DMF solution of malononitrile to a mixture of sulfur, propionaldehyde and triethylamine in DMF. The anion of amino thiophene 22 underwent a nucleophilic aromatic substitution with 2-fluoronitrobenzene to provide 23. The nitro group was reduced with stannous chloride and the resulting anihne cyclized with the cyano group to form amidine 24. Finally, a mixture of N-methylpiperazine and 24 were refluxed in DMSO/toluene to afford olanzapine (2). 

Secondary and tertiary dialkylcuprates, lithium dialkenyl-, and even diphenyl-cuprates, add in very good yields to the reactive propionaldehyde diethyl acetal. The syn addition products may be trapped with a variety of electrophiles such as alkyl, alkenyl, alkynyl and aryl halides. The method has been used for the synthesis of several natural products. Substituted alkynic acetals also react with lithium dialkylcuprates in ether to furnish stable dialkenylcuprates of type (128) which do not eliminate to the corresponding alkoxy allenes (129) if the temperature is maintained below -20 C.164-179... 

NMA+) and 2,4,6-triphenyl-pyrylium tetrafluoroborate (TPP+) in the presence of biphenyl as cosensitizer were suitable for this reaction [174], The assumed mechanism of formation of do by this cosensitization is shown in Scheme 7. Reaction of do with H-donors such as te/t-butylmethylether, propionaldehyde and alcohols results in the formation of 1 1 adducts, the 1-substituted 1,2-dihydro-[60]fullerenes. Product structure support a H-abstraction process [212,213] rather than nucleophilic addition. In Scheme 8, the general formation of 1-substituted l,2-dihydro-[60]fullerenes is shown. Selected examples of the products obtained by this method are summarized in Table 10. 

Among important products manufactured in this manner are substituted propionaldehyde from corresponding substituted ethylene, normal and rso-butyr aldehyde from propylene, iso-octyl alcohol from heptene, and trimethylhexyl alcohol from di-isobutylene. 

The homogeneous complex RhCl(dpm)3 acts also as hydroformylation catalyst [159], Upon illumination of the catalytic photosystem Ru(bpy) +/ascorbic acid/RhCl(dpm)3- in the presence of ethylene and carbon monoxide, propionaldehyde is obtained as photoproduct. Similarly, propene yields the hydroformylation product butyraldeyde. The facts that no hydrogenation products are produced in this assembly, and that hydridocarbonyl-tris-(diphenylphos-phinobenzene-3-sulphonate) rhodium(I), RhHfCOXdpm) -, substitutes RhCl(dpm)3- as catalyst in the photosystem to yield the hydroformylation products at similar efficiency, suggest that the homogeneous catalyst RhClfdpmJj -is transformed into a new catalytic species under CO. A possible route for the interconversion of RhCl(dpm)3 into the hydroformylation catalyst is provided in Scheme 4. 

Due to the increased reactivity of the aldehyde, alkyl-substituted nitroolefins can also be used as substrates. Nevertheless, these reactions are usually low-yielding and afford moderate selectivity. Alexakis has shown, however, that the bispyrrolidine 5-catalyzed additions may be used in multistep synthesis. The addition of propionaldehyde 34 to nitroolefin 33 resulted an approximate 2 3 mixture of anti/syn isomers in 92% yield and in high ee (93%), allowing the asymmetric synthesis of (—)-botryodiplodin (Scheme 2.46) [23b]. 

Ketones and Aldehydes The R2C=0 and the RCH=0 carbon atoms absorb in a characteristic region. Acetone absorbs at 203.3 ppm, and acetaldehyde at 199.3 ppm. Alkyl substitution on the a-carbon causes a shift to the left of the C=0 absorption of 2-3 ppm until steric effects supervene. Replacement of the CH3 of acetone or acetaldehyde by a phenyl group causes a shift to the right of the C=0 absorption (acetophenone, 195.7 ppm benzaldehyde. 190.7 ppm) similarly, a,/3-unsaturation causes shifts to the right (acrolein, 192.1 ppm, compared with propionaldehyde, 201.5 ppm). Presumably, charge delocalization by the benzene ring or the double bond makes the carbonyl carbon less electron deficient. 

By contrast, substitution in position 7 is much easier thanks to the well-known Minisci reaction, which involves a nucleophilic radical attack on a protonated quinoline [31]. Moreover, due to the unavailability of position 2 of the quinoline nucleus, the reaction shows complete regioselectivity. Minisci alkylation with an ethyl radical produced in situ by decarbonylation of propionaldehyde is a crucial step in the process of preparation of irinotecan (4) (Scheme 16.6) [32], whereas the same kind of reaction led to the semisynthesis (Scheme 16.7) of gimatecan (9)[33], silatecan (10)[34], and belotecan (ll)[35j. This last compound entered clinical practice in Korea in 2005. 

Table 12. Oxidation potentials, Ep, of pora-substituted 2-aryl-propionaldehydes 88 and their tautomeric enols 89 in acetonitrile/DMSO [171] compared with calculated , 2 (89)- The enol content was taken from Ref. [187]...

An alternative approach to [26]porphyrins-(5.1.5.1) was devised by Franck and coworkers and was reported in 1991 This approach, outlined in Scheme 4.2.5, involves a more linear synthetic strategy than was employed by LeGoff. Specifically, it involves preparing first the tetravinylogous dideoxybiladiene-ac dihydrobromide precursor 4.82 and then reacting it with formaldehyde. Oxidation in situ with DDQ then affords the [26]porphyrin-(5.1.5.1) 4.83a in 43% yield. The C(14)-substituted [26]porphyrins-(5.1.5.1) 4.84 and 4.85 were prepared in an analogous manner (64% and 5% yield, respectively) by condensing 4.82 with benzalde-hyde or propionaldehyde as appropriate. 

Yet another development which is worth mentioning in this context is the 5n substitution of acetals of unsaturated carbonyl compounds. The phenomenon that the reaction of an allylic acetal with a Grignard reagent in the presence of CuBr may occur as a vinylogous substitution with double bond shift has been long known.The reaction can be utilized in an efficient synthesis of 3-substituted propionaldehydes using the acrolein acetal as a homoenolate cation equivalent (Scheme 38). ... 

Because of the commercial importance of fosfomycin, it is not surprising that several important and attractive synthetic methods are reported in patents. They include, for example, precursors such as dimethyl hydroxymethylphosphonate, dimethyl, dibenzyl, and diallyl formylphosphonate, trimethyl phosphite and 2-cyano-1-hydroxypropene, 9 trialkyl phosphite and 2-chloro-propionaldehyde or 2-acetoxypropionaldehydc, diethyl chloromethylphosphonate, dibenzyl phosphite, and 1-chloro-1,2-propylene oxide,2 propynylphosphonic acid, propenylphos-phonic acid,2 2-chloro-(czT-l,2-epoxypropyl)phosphonic acid, and extrusion reactions on thermolysis. The resolution of racemic acids has also been reported. In search of new effective antibiotics, a large variety of substituted epoxyethylphosphonic acids have been pre-pared.249... 

Kiesel, M., Haug. E., and Kantlehner, W., Qrthoamidcs. Part 50. Contribution to the chemistry of propionaldehyde aminals. Synthesis and transformalions to push-pull-substituted buta-1,3-dienes, cyclobutanes, vinylogous amidinium salts and 1,2,3-triazoles, J. Prakt. Chem./Chem.-Ztg., 339, 159,... 

Chloramine-T, the sodium salt of A-chloro-p-tolucncsulfonamidc, tosylami-nates a number of in situ generated enamines of a-substituted propionaldehydes (see Eq. 78), a-substituted arylacetaldehydes, and methyl arylmethyl ketones.78... 

The single exception to 1,4-addition is 4-cyano-l,2-naphthoquinone which reacted normally with aromatic aldehydes but underwent 8>144) nuclear substitution to give l,2-dihydroxy-3-acyl-4-cyanonaphthalenes (69) with acetaldehyde (unspecified yield) and propionaldehyde (17% yield). The structural assignments were based on chemical and spectro-... 

An interesting reaction between pyrazol-3-one 62 and A,A -diphenylformamidine 576 has appeared in a patent (69GEP1800581) (Scheme 172). The reaction took place by heating these compounds in a mixture of acetaldehyde and triethylamine and gave, in excellent yield, ( /Z)-4-[3-(pyrazol-4-yl)prop-2-enylidene]pyrazol-3-one 581. The proposed mechanism suggests initial substitution and loss of aniline, addition of acetaldehyde to the a,/1-moiety of pyrazol-3-one, loss of aniline from 578 to a 3-(5-oxo-pyrazol-4-ylidene)propionaldehyde 579c, addition of a second molecule of 62 to... 

Indoles undergo Michael additions in the presence of acid catalysts. Gold-catalyzed conjugate additions of indoles with enones led to the formation of indol-3-yl propanones <04SL944>. With 3-substituted indole substrates, the reactions proceeded to give the corresponding 2-substituted indoles. Homotryptamines were formed in a one-pot sequence that involved a Michael addition by indole substrates to acrolein imine derivatives followed by a reductive amination of the indole propionaldehyde intermediates <04TL3803>. 

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