Subject reaction with benzaldehyde

The ring expansion of the carbene dioxolane 208 occurred in the presence of Rh(n) catalyst. The reaction proceeded presumably via the intermediate ylide 209, which was subjected to the reaction with benzaldehyde in the presence of Lewis acid to give a mixture of the dioxocine 210, as the major product, as well as dioxocane 211 (Scheme 24) <2003JOC10040>. Compounds 210 and 211 were separated and the yy -conformation of 210 was determined by X-ray crystallographic analysis. The stereochemistry of 211 was also established by X-ray crystallography. 

In the chromium-mediated reaction of 1-fluoro-l-bromo-l-alkene with an aldehyde, the ( )-isomer reacts more quickly than the (Z)-isomer. Therefore, when a mixture of stereoisomer 42a was subjected to the reaction with benzaldehyde in the presence of CrCl2 and Ni catalyst, a (Z)-isomer of allylic alcohol 51 was selectively formed [77, 78] (Scheme 21). The reaction proceeds through an alkenylchromium species 52, and the formation of the ( )-alkenylchromium species is much faster than that of the (Z)-isomer. Actually, the reactimi of a pure (Z)-isomer of 1 -fluoro-1 -bromo-1-alkene with aldehyde is sluggish, and the corresponding ( )-isomer of the product was obtained in low yield or not obtained at all. Therefore, a good method for the synthesis of ( )-51 has not yet been reported. 

Chiral salen chromium and cobalt complexes have been shown by Jacobsen et al. to catalyze an enantioselective cycloaddition reaction of carbonyl compounds with dienes [22]. The cycloaddition reaction of different aldehydes 1 containing aromatic, aliphatic, and conjugated substituents with Danishefsky s diene 2a catalyzed by the chiral salen-chromium(III) complexes 14a,b proceeds in up to 98% yield and with moderate to high ee (Scheme 4.14). It was found that the presence of oven-dried powdered 4 A molecular sieves led to increased yield and enantioselectivity. The lowest ee (62% ee, catalyst 14b) was obtained for hexanal and the highest (93% ee, catalyst 14a) was obtained for cyclohexyl aldehyde. The mechanism of the cycloaddition reaction was investigated in terms of a traditional cycloaddition, or formation of the cycloaddition product via a Mukaiyama aldol-reaction path. In the presence of the chiral salen-chromium(III) catalyst system NMR spectroscopy of the crude reaction mixture of the reaction of benzaldehyde with Danishefsky s diene revealed the exclusive presence of the cycloaddition-pathway product. The Mukaiyama aldol condensation product was prepared independently and subjected to the conditions of the chiral salen-chromium(III)-catalyzed reactions. No detectable cycloaddition product could be observed. These results point towards a [2-i-4]-cydoaddition mechanism. 

To demonstrate the feasibility of organic synthesis using this support, the authors immobilized a N-Boc protected glycin (22) on the support (Scheme 7.5). After deprotection imine formation readily occurs with an excess of benzaldehyde. The product was then subjected to a Staudinger reaction with phenoxyacetylchlor-ide to yield the polymer supported / -lactam (26) which could be released to give the yS-lactam (27) with TEA in methanol. 

The use of chiral azomethine imines in asymmetric 1,3-dipolar cycloadditions with alkenes is limited. In the first example of this reaction, chiral azomethine imines were applied for the stereoselective synthesis of C-nucleosides (100-102). Recent work by Hus son and co-workers (103) showed the application of the chiral template 66 for the formation of a new enantiopure azomethine imine (Scheme 12.23). This template is very similar to the azomethine ylide precursor 52 described in Scheme 12.19. In the presence of benzaldehyde at elevated temperature, the azomethine imine 67 is formed. 1,3-Dipole 67 was subjected to reactions with a series of electron-deficient alkenes and alkynes and the reactions proceeded in several cases with very high selectivities. Most interestingly, it was also demonstrated that the azomethine imine underwent reaction with the electronically neutral 1-octene as shown in Scheme 12.23. Although a long reaction time was required, compound 68 was obtained as the only detectable regio- and diastereomer in 50% yield. This pioneering work demonstrates that there are several opportunities for the development of new highly selective reactions of azomethine imines (103). 

The BFD mutant library generated by epPCR was expressed in microtiter plates and 8000 clones were subjected to the carboligation assay with benzaldehyde 4 and dimethoxyacetaldehyde 8 as the substrates. The reaction was incubated for 24 h at 30 °C as suggested from experiments using the positive control strain... 

Reactions of 4,7-phenanthroline-5,6-dione have been the subject of considerable study. It is reduced to 5,6-dihydroxy-4,7-phenanthroline by Raney nickel hydrogenation226,249 or by aromatic thiols in benzene,262 and oxidized by permanganate to 3,3 -bipyridyl-2,2 -dicarboxylic acid.263 It forms bishemiketals with alcohols226 and diepoxides with diazomethane.226 The diepoxides by reaction with hydrochloric acid form diols of type 57, R = Cl, which on oxidation with lead tetraacetate give 3,3 -bipyridyl diketones of type 58, R = Cl. Methyl ketones of type 58, R = H, are also obtained by lead(IV) acetate oxidation of the diol 57, R = H, obtained by lithium aluminum hydride reduction of 57, R = Cl. With phenyldiazomethane and diphenyldiazomethane the dione forms 1,3-dioxole derivatives,264,265 which readily hydrolyze back to the dione with concomitant formation of benzaldehyde and benzophenone, respectively. 

The research on asymmetric organozinc additions to carbonyl compounds started in 1984 when Oguni and Omi obtained 49% e.e. in the reaction of diethylzinc with benzaldehyde catalyzed by (X)-leucinol. Since then, a huge number of chiral (see Chiral) catalysts, mostly derived from amino alcohols, have been developed and the subject has been extensively reviewed. 63.264 jjjg highly enantioselective (see Electrophile) ligand (—)-3-exo-dimethylaminoisobomeol [(-)-DAIB] developed by Noyori and coworkers in 1986 is still used even if its application is mostly limited to aromatic and heteroaromatic aldehydes (equation 62). As shown by previous studies, chiral (see Chiral) ligands have a dual... 

Problem 26.3 (a) Malonic ester reacts with benzaldehyde in the presence of piperidine (a secondary amine. Sec. 31.12) to yield a product of formula C14H16O4. What is this compound, and how is it formed (This is an example of the Knoevenagel reaction. Check your answer in Problem 21.22 (f), p. 714.) (b) What compound would be obtained if the product of (a) w ere subjected to the sequence of hydrolysis, acidification, and heating (c) What is another way to synthesize the product of (b) ... 

Bach d has reviewed photochemical (2 + 2)-cycloaddition reactions including oxetane-forming processes and the stereochemical aspects of the reactions are highlighted. Earlier studies by the same author reported the results of irradiation of the alkene (88) in benzene with benzaldehyde to give the oxetane (89). These 3-oxetanols have been subjected to further study and have been... 

The phosphonium salt was subjected to a Wittig reaction with a dimethylformamide solution of 212 mg (2 mmol) of benzaldehyde and sodium methoxide as a base. The solution was heated at about 80 °C and stirred for 8 h. After cooling, water was added and the mixture extracted with toluene. The combined extracts were washed with water, dried over MgS04 and the solvent evaporated. After column chromatography of the residue on aluminium oxide with CCI4 as the eluant the cw-isomer of 2-styrylbenzo[c]phenanthrene was isolated, whereas the traiw-isomer was obtained after elution with a mixture of hexane and toluene (1 5). The overall yield was 65% (mp cis. 142 - 144 °C, mp trans-. 224 - 226 °C). 

The degree of stereoselectivity of aldol reactions of simple cyclohexanone enolates has been a subject of some confusion. For cyclohexanone itself, it has been reported that reaction of the lithium enolate with benzaldehyde gives Ae two isomeric aldols (Scheme 1) in ratios of 52 48 in THF at -78 C and 50 50 in dimethoxyethane at -20 C. On the other hand, Seebach reports ratios of 79 21 at -78 C and 85 15 at -150 C. ° Hirama and coworkers reinvestigated the reaction of the lithium enolate of cyclohexanone with benzaldehyde (Scheme 1) and found anti.syn ratios of about 82 18 at -78 C. The ratio is... 

In the presence of piperidine in benzene, benzaldehyde reacts with diethyl (nitromethyl)-phosphonate to afford at 67% yield of diethyl (2-hydroxy-l-nitro-2-phenylethyl)phos-phonate, presumably as a mixture of diastereoisomers. However, a similar reaction with 4-nitrobenzaldehyde leads to phosphorus-carbon bond cleavage and the formation of 1-nitro-2-(4-nitrophenyl)ethane. The converse procedure, i.e. a reaction which involves a nitroalkane and an (oxoalkyl)phosphonic diester, is also subject to certain restrictions. The base-catalysed nucleophilic additions of nitromethane to dialkyl acetylphosphonates (Scheme 7 R = Me) to give dialkyl [(1-hydroxy-l-nitromethyl)alkyl]phosphonates have... 

Acetals of 3-bromo-4-fluoro benzaldehydes have been successfully subjected to the Ullmann reaction with several phenolates and anilines, leaving the fluorine untouched, producing the following intermediates ... 

Nolen et al. also reported the self-condensation reaction of butyraldehyde and the cross-aldol condensation of benzaldehyde with acetone (Figs. 9.58 and 9.59) at 250°C. The butyraldehyde self-condensation produced a number of products, including 2-ethyl-2-hexenal, 2-butyl-2-butenal, and 2-ethyUiexanal. The results from the condensation of butyraldehyde indicate that a 40% yield of 2 -ethyl-2 -hexenal is achieved before the formation of by-products becomes dominant. In addition, investigations of the back reaction show that a substantial quantity of butyraldehyde is formed when 2-ethyl-2-hexenal is subjected to water at 250°C. The condensation reaction of benzaldehyde with acetone produced a 15% yield of trans-4-phenyl-3-buten-2-one in 5 h and very small quantities of trans,trans-dibenzylidene acetone during this same period of time. The authors suggest that the low yield could be a result of equilibrium limitations. 

Asymmetric allylation of aldehydes with allyhc agents catalyzed by Lewis acid is a practical method for synthesizing optically active hranoallylic alcohols [10]. The chloro complex 1 serves as an efficient catalyst for asymmetric allylation of aldehydes with allylstannane [8, 9, 11]. In the presence of 5 mol% of the benzyl-phebox-Rh complex 1-Bn, the coupling reaction of benzaldehyde with allyltributyl-stannane in CH2CI2 at room temperature proceeded smoothly to provide the corresponding homo-aUyl alcohol 7a in 88% yield with 61% ee (Scheme 2). When methaUylstannane was subjected to the reactiOTi, enantioselectivity of the allylated product 8 significantly increased to be over 90% ee. 

Gosh independently reported another anti-selective aldol addition process employing aminoindanol-derived esters 114 (Equation 11) [72]. These were subjected to enolization with excess TiCl, and Hiinig s base to furnish titanium 2-enolates, as determined by NMR spectroscopy. Addition reactions with a variety of aliphatic and unsaturated aldehydes, precomplexed with TiCl4, furnished the anti aldol adducts such as 116 in 44—97% yields and up to 99 1 anti/syn ratios of diastereomers. The stereochemical outcomes of the reactions have been attributed to chelated Zimmerman-Traxler transition state structures, such as 115. It is interesting to note that benzaldehyde, as the only aromatic aldehyde examined, yielded a 1 1.1 mixture of antijsyn products. 

Pyrimidinopyrazines related to folic acid have been investigated in some detail for their antimeta-bolic and antineoplastic activities. A related compound, which lacks one nitrogen atom, has been described as an antiproliferative agent, indicating it too has an effect on cell replication. Aldol condensation of the benzaldehyde 99 with ethyl acetoacetate gives the cinnamate 100. This is then reduced catalytically to the acetoacetate 101. Reaction of that keto ester with 2,4,6- triami-nopyrimidine gives the product 102 which is subsequently chlorinated (103) and subjected to hydrogenolysls. There is thus formed piritrexim (104) [17]. 

The Darzens reaction can also proceed in the presence of a chiral catalyst. When chloroacetophenone and benzaldehyde are subjected to asymmetric Darzens reaction, product 89 with 64% ee is obtained if chiral crown ether 88 is used as a phase transfer catalyst (Scheme 8-30).69... 

Concentrated sulfuric acid (0.316 mol) was added over lh to dimethyl sulfide (0.316 mol), the temperature of the reaction mixture being kept below 30°C. Methanol (0.156 mol) was then added over 30 min with the temperature below 35°C. After the mixture had been stirred for 5h, t-BuOH (0.048 mol) was added to it followed by potassium hydroxide (0.58 mol) in 10 equal aliquots over 2.5 h. Benzaldehyde (0.15 mol) was added after the seventh KOH aliquot0 and an alkaline pH had been achieved. The mixture was stirred at room temperature for 12 h and subjected to conventional pentane/aqueous work-up. Styrene oxide was isolated in a 55% yield. 

The reaction may alternatively be carried out by boiling the benzaldehyde vigorously under reflux for 2 hours with a solution of 20 g of potassium hydroxide in 90 ml of water, and then working up the cooled reaction mixture as described above. Reaction is normally complete under these conditions the extent of the reaction may be determined by subjecting the crude ether extract, before the latter is washed with bisulphite solution, to g.l.c. analysis on a 1.5 m column of Chromosorb W with 10 per cent of Carbowax as the stationary phase, at 156 °C with a nitrogen flow rate of 40ml per minute. The retention times of benzaldehyde and benzyl alcohol are approximately 2.7 and 9.7 minutes respectively. 

Scheme 16 shows parallel syntheses of cyclic and acyclic amide compounds. Fluorous benzaldehydes were first subjected to reductive amination reactions. The resulting amines were then reacted with isocyanates to form substituted hydantoin rings 14 or with benzoyl chlorides to form amides 15. Purified F-sulfonates were used for palladium-catalyzed cross-coupling reactions to form corresponding biaryl 16 [31] and arylsulfide 17 [32] products, respectively. 

---