Cinnamaldehyde, 1,2-additions reactions

Physical and Chemical Properties. The (F)- and (Z)-isomers of cinnamaldehyde are both known. (F)-Cinnamaldehyde [14371-10-9] is generally produced commercially and its properties are given in Table 2. Cinnamaldehyde undergoes reactions that are typical of an a,P-unsaturated aromatic aldehyde. Slow oxidation to cinnamic acid is observed upon exposure to air. This process can be accelerated in the presence of transition-metal catalysts such as cobalt acetate (28). Under more vigorous conditions with either nitric or chromic acid, cleavage at the double bond occurs to afford benzoic acid. Epoxidation of cinnamaldehyde via a conjugate addition mechanism is observed upon treatment with a salt of /-butyl hydroperoxide (29). 

Yamamoto has recently described a novel catalytic, asymmetric aldol addition reaction of enol stannanes 19 and 21 with aldehydes (Eqs. 8B2.6 and 8B2.7) [14]. The stannyl ketones are prepared solvent-free by treatment of the corresponding enol acetates with tributyltin methoxide. Although, in general, these enolates are known to exist as mixtures of C- and 0-bound tautomers, it is reported that the mixture may be utilized in the catalytic process. The complexes Yamamoto utilized in this unprecedented process are noteworthy in their novelty as catalysts for catalytic C-C bond-forming reactions. The active complex is generated upon treatment of Ag(OTf) with (R)-BINAP in THF. Under optimal conditions, 10 mol % catalyst 20 effects the addition of enol stannanes with benzaldehyde, hydrocinnamaldehyde, or cinnamaldehyde to give the adducts of acetone, rerf-butyl methyl ketone (pinacolone), and acetophenone in good yields and 41-95% ee (Table 8B2.3). 

C) furnishes the acetoxy alcohol (24) in 86% isolated yield, with acetophenone recovered in 93% GLC yield (see equation 9). With an unsaturated aldehyde, such as cinnamaldehyde, a 1,2-addition reaction is observed in the presence of BF3-OEt2, but only the 1,4-addition product is obtained if the reaction is performed with TMS-Cl as an addtive (see Scheme 9). ... 

The catalytic, enantioselective aldol addition reaction generates products that can serve as versatile precursors to useful building blocks for asymmetric synthesis (Eq. 26). For example, treatment of cinnamaldehyde adduct 177 with LiAl(HNBn)4178 afforded the crystalline amide 179 (73%). Heating in -BuOH converted 177 to ester 180 (81%). Heating in alkaline methanol yielded (79%) the crystalline lactone 181. The synthetic utility of adducts 179 and 180 is enhanced by the stereoselective reaction methods that have been developed for their reduction to the corresponding syn and anti 3,5-diols [103,104]. 

As shown in the case of cinnamaldehyde, addition to the carbonyl functionality occurs in preference to attack at the electron-poor double bond. The extent to which stereogenic aldehydes can control the stereochemical course of these cycloadditions is discussed in Section 1.6.1.2.3.2. The success of the tin-based cocatalyst to induce reaction is explained in terms of the formation of an intermediate stannyl ether which exhibits greater reactivity towards 7t-allyl palladium cations than free alkoxide ions. The addition to ketones is less general and one of the more successful examples is given. 

Manufacture. Cinnamaldehyde is routinely produced by the base-cataly2ed aldol addition of ben2aldehyde /7(9(9-with acetaldehyde [75-07-0], a procedure which was first estabUshed in the nineteenth century (31). Formation of the (H)-isomer is favored by the transition-state geometry associated with the elimination of water from the intermediate. The commercial process is carried out in the presence of a dilute sodium hydroxide solution (ca 0.5—2.0%) with at least two equivalents of ben2aldehyde and slow addition of the acetaldehyde over the reaction period (32). 

A 500-ml, three-necked, round-bottom flask is equipped with a condenser, a dropping funnel, and a thermometer in the reaction mixture. In the flask is placed a mixture of 85% hydrazine (115 ml, 118 g) and 225 ml of 95% ethanol with a few boiling chips. The solution is brought to reflux (mantle) and cinnamaldehyde (100 g, 0.76 mole) is added dropwise over about 30 minutes followed by an additional 30 minutes of refluxing. A still head is attached to the flask and volatiles (ethanol, water, hydrazine hydrate) are slowly distilled at atmospheric pressure until the pot temperature reaches 200° (about 3 hours). Hereafter, phenylcyclopropane is collected over the range 170-180°. When the pot temperature exceeds 250°, the recovery is complete. The crude product (55-65 g) is washed twice with 50-ml portions of water and dried (anhydrous potassium carbonate). Distillation under vacuum through a short column affords the product, bp 60°/13 mm, 79-80°/37 mm, n f 1.5309, about 40 g (45%). 

The lithio-derivative derived from cyclohexyl phenyl sulfone underwent 1,2-addition to cyclohexenylideneacetaldehyde or cinnamaldehyde to give the corresponding / -hydroxysulfones387. Reactions of 2,2-dimethyl-4-lithio-1,3-oxathiane 3,3-dioxide 308... 

Other excellent results have been reported by Kang et al. for the addition of ZnEt2 to aldehydes by using chiral cyclic amino thiol ligands depicted in Scheme 3.7. A total enantioselectivity was obtained when (lR,25)-l-phenyl-2-piperidinopropane-1-thiol was used as the ligand in the reactions of substituted benzaldehydes. However, -hexanal and traw -cinnamaldehyde could only be... 

We have shown that the direct arylation of acrolein toward the synthesis of cinnamaldehyde derivatives was an efficient procedure. Using the palladacycle 1 as catalyst, substituted aldehydes 3 were prepared with up to 87% isolated yield from condensed aiyl bromides (Scheme 21.1, Route 1) that was extended successfully to heteroaiyl bromides, like bromoquinolines (6). Alternatively, the acrolein diethyl acetal was used as olefin and a selective formation of the saturated ester 4 was attained under the same reaction conditions (Scheme 21.1, Route 2). The expected aldehydes 3 were, however, obtained from most of the aiyl halides used under modified conditions. It was shown that the addition of n-Bu4NOAc in the medium... 

Et2Zn also participates in the reductive coupling as a formal hydride source. Results for the Ni-catalyzed, Et2Zn-promoted homoallylation of carbonyl compounds with isoprene are summarized in Table 7 [30]. Et2Zn is so reactive that for the reaction with reactive aromatic aldehydes it causes direct ethylation of aldehydes, and the yields of homoallylation are diminished (runs 1 and 2). Unsaturated aldehydes seem to be subject to the Michael addition of Et2Zn. Accordingly, for the reaction with cinnamaldehyde, none of the expected homoallylation product is produced instead, the 1,4-addition product of Et2Zn, 3-phenylpentanal is produced exclusively (run 3). 

A 1-1. three-necked round-bottomed flask, fitted with a dropping funnel and a mechanical stirrer, is cooled in an ice-salt mixture. To the flask are added 55.5 g. (50 ml., 0.42 mole) of freshly distilled cinnamaldehyde (Note 1) and 225 ml. of acetic anhydride. When the temperature of the solution has reached 0-5° a solution of 18 ml. of concentrated nitric acid (sp. gr. 1.42) in 50 ml. of glacial acetic acid is added slowly through the dropping funnel while the mixture is stirred. The time of addition is 3-4 hours, during which the temperature is kept below 5°. After the addition is complete, the mixture is allowed to warm slowly to room temperature. The. reaction flask is then dismantled and stoppered, and the reaction mixture is allowed to stand 2 days. 

The stereoselective addition of the titanium enolate of A-acetyl-4-phenyl-l,3-thiazolidine-2-thione 153 to the cyclic A-acyl iminium ion 154 is utilized in the synthesis of (-)-stemoamide, a tricyclic alkaloid <06JOC3287>. The iminium ion addition product 155 undergoes magnesium bromide-catalyzed awtz-aldol reaction with cinnamaldehyde 156 to give adduct 157, which possesses the required stereochemistry of all chiral centers for the synthesis of (-)-stemoamide. 

Superior yields of ethers from aldehydes are obtained by the use of several other electrophilic species. The addition of 5 mol% of trityl perchlorate to a mixture of triethylsilane and 3-phenylpropanal in dichloromethane at 0° produces an 83% yield of bis-(3-phenylpropyl) ether within 10 minutes (Eq. 176),329 Reductive polycondensation of isophthalaldehyde occurs with two equivalents of triethylsilane in the presence of 10 mol% of trityl perchlorate to give 40-72% yields of polyether with average molecular weights ranging from 6,500 to 11,400 daltons (Eq. 177).337 Addition of one equivalent of an alkoxytrimethylsilane to the reaction mixture produces unsymmetrical ethers in good to excellent yields. Thus, a mixture of (ii)-cinnamaldehyde, 3-phenylpropoxytrimethylsilane, and triethylsilane in dichloromethane reacts under the influence of a catalytic amount of trityl perchlorate to give the unsymmetrical ether in 88% yield (Eq. 178).329... 

Selection of the reaction conditions brings about a complete reversal between 1,2- and 1,4-addition in the reaction of cinnamaldehyde (Scheme 83).386... 

The synthesis of y-lactams has been achieved under similar reaction conditions (Table 18) [124]. Initially, Bode and co-workers screened a variety of acyl imines in order to find suitable electrophiles. Control experiments provided evidence for carbene addition to the acyl imine, yielding a stable complex with complete inhibition of the desired reactivity. Reversibility of this addition was key to the success of the reaction. A -4-Methoxybenzenesulfonyl imines 212 proved to be the most efficient partners for lactamization with cinnamaldehydes 228 to provide y-lactams 229 in moderate yields and good diastereoselectivities. Notably, no benzoin or S tetter products or their corresponding derivatives were observed during this reaction. 

Ogilvie monitored the Diels-Alder reaction between cinnamaldehyde and cyclopentadiene by H NMR using his hydrazide catalyst 18 and was able to conclude that under the reaction conditions adopted (18-TfOH 100 mol% CDjNOj/D O (19 1) 0.1 M) cycloaddition was the rate limiting step of the catalytic cycle, iminium ion formation and hydrolysis being rapid [48]. In addition, it was also shown that under these reaction conditions the key cycloaddition step was reversible. Although this unexpected reversibility was slow, the possibility of exploiting this in a dynamic resolution procedure appears tempting. 

In the Mukaiyama aldol additions of trimethyl-(l-phenyl-propenyloxy)-silane to give benzaldehyde and cinnamaldehyde catalyzed by 7 mol% supported scandium catalyst, a 1 1 mixture of diastereomers was obtained. Again, the dendritic catalyst could be recycled easily without any loss in performance. The scandium cross-linked dendritic material appeared to be an efficient catalyst for the Diels-Alder reaction between methyl vinyl ketone and cyclopentadiene. The Diels-Alder adduct was formed in dichloromethane at 0°C in 79% yield with an endo/exo ratio of 85 15. The material was also used as a Friedel-Crafts acylation catalyst (contain-ing7mol% scandium) for the formation of / -methoxyacetophenone (in a 73% yield) from anisole, acetic acid anhydride, and lithium perchlorate at 50°C in nitromethane. 

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