Aldehydes nucleophilic attack

Section 17 2 The carbonyl carbon is sp hybridized and it and the atoms attached to It are coplanar Aldehydes and ketones are polar molecules Nucleophiles attack C=0 at carbon (positively polarized) and electrophiles especially protons attack oxygen (negatively polarized)... 

Another very important reaction initially involving nucleophilic attack on an aldehyde carbonyl is the Wittig reaction. An yUd adds to the carbonyl forming a betaine intermediate which then decomposes to produce an olefin and a tertiary phosphine oxide. 

It is also possible to carry out the aldol condensation under acidic conditions. The reactive nucleophile is then the enol. The mechanism, as established in detail for acetaldehyde, involves nucleophilic attack of the enol on the protonated aldehyde. 

The reactivity of aldehydes and ketones toward cyanide may be influenced by the steric and/or electronic properties of the carbonyl substituents, X. Examine spacefilling models of formaldehyde (X=H), acetone (X=Me), and benzophenone (X=Ph). Which compound offers the least steric hindrance to nucleophilic attack The most ... 

O Nucleophilic attack on the ketone or aldehyde by the lone-pair electrons of an amine leads to a dipolar tetrahedral intermediate. 

Although intermediate 2 is terminated at both ends by electrophilic carbonyl groups, the aldehydic function at C-7 is inherently more reactive, and thus more susceptible to a nucleophilic attack, than the methoxycarbonyl group at C-l. As a result, it should be possible to selectively engage the aldehyde carbonyl of intermedi-... 

Bromomethyl)biphenyl-2-carbaldehyde (45) undergoes ring closure with arylamines to give 6-substituted 5//-dibenz[c.t,]azepinium bromides 46 via initial nucleophilic attack by the amine at the aldehyde function.92... 

Lewis acids, particularly the boron trifluroride diethyl ether complex, are used to promote the reaction between allyl(trialkyl)- and allyl(triaryl)stannanes and aldehydes and ketones52-54. The mechanism of these Lewis acid promoted reactions may involve coordination of the Lewis acid to the carbonyl compound so increasing its reactivity towards nucleophilic attack, or in situ transmetalation of the allyl(trialkyl)stannane by the Lewis acid to generate a more reactive allylmetal reagent. Which pathway operates in any particular case depends on the order of mixing of the reagents, the Lewis acid, temperature, solvent etc.55- 58. 

One limitation of these noncatalyzed allyl(trialkyl)- and allyl(triaryl)stannane-aldehyde reactions is the high temperature required unless the aldehyde is activated towards nucleophilic attack. Allyltin halides are much more reactive because of their enhanced Lewis acid character however 2-butenyltin halides show reduced syn I anti selectivity45, and give other products including linear homoallylic alcohols and tetrahydropyrans47. 

Good Cram selectivity is observed for Lewis acid induced reactions between allylstannanes and aldehydes with alkyl-substituted a-chiral centers66,87. This enhanced Cram selectivity may be due to the effect of the Lewis acid on the trajectory of nucleophilic attack on the aldehyde66. 

There are expressions of uncertainty concerning the mechanism of the first step of the Strecker amino acid synthesis13-17. The reaction can proceed via the formation of an imine and subsequent nucleophilic attack of cyanide (path ). Alternatively, it has been speculated that the reaction of the aldehyde with hydrogen cyanide furnishes a cyanohydrin (path ), which then is subjected to a nucleophilic displacement of the hydroxy group by the amino function. 

It has long been known that a, / -unsaturated sulfones resemble a, /i-unsaturated ketones and aldehydes in undergoing addition reactions with nucleophilic reagents43. These reactions are initiated by nucleophilic attack at the carbon to the sulfone group ... 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

Selenoaldehydes 104, like thioaldehydes, have also been generated in situ from acetals and then directly trapped with dienes, thus offering a useful one-pot procedure for preparing cyclic seleno-compounds [103,104], The construction of a carbon-selenium double bond was achieved by reacting acetal derivatives with dimethylaluminum selenide (Equation 2.30). Cycloadditions of seleno aldehydes occur even at 0 °C. In these reactions, however, the carbon-selenium bond formed by the nucleophilic attack of the electronegative selenium atom in 105 to the aluminum-coordinated acetal carbon, may require a high reaction temperature [103], The cycloaddition with cyclopentadiene preferentially gave the kinetically favorable endo isomer. 

The aldehyde acid reactions have already been described generally in Chapter 2. There it was pointed out that a nucleophilic attack at a carbonyl group is particularly easy when this is attached to an aromatic ring that bears an electron withdrawing group at position 4. The reactivity of the carbonyl group is greatly increased in acid medium ... 

The cyclization involves a nucleophilic attack of the malonic ester car-banion on the carbonyl carbon atom of the aldehyde, and the substituted malonic ester carbanion attacks the electron-deficient carbon atom bearing the iodine atom, or in the reverse order, to give 119. The hydroxyl group generated in the first step of the reaction attacks the carbon atom, giving the pyranose product. 

Subsequent nucleophilic attack on the aldehyde then forms the P-C bond. Protonolysis with i-PrOH gives the product and regenerates the bis(isopropoxide) form of the catalyst alternatively, reaction with 25 would reform the next intermediate [21]. 

In the proposed mechanism (Scheme 5-33), both the phosphite and the aldehyde are coordinated to the catalyst before nucleophilic attack forms the P-C bond. Slow addition of the aldehyde was found to improve ees it was suggested that this minimizes unselective attack of the activated phosphite on free aldehyde instead of the desired selective attack on complexed aldehyde [26]. In related chemistry with para-anisaldehyde, Shibuya found that ees also depended on the rare earth (La, Eu, Sm) in the heterobimetallic catalyst [24]. 

The relatively basic (hydroxyalkyl)phosphines act toward LMCs as reductants and, compatible with this, also as strong nucleophiles. We have studied such reactions in aqueous and D2O solutions by P-, H-, and C-NMR spectroscopies (including 2D correlation methods), product isolation and, when possible, X-ray analysis of isolated compounds or their derivatives. Thus, aromatic aldehyde moieties present in lignin (e.g., 3) are reduced to the corresponding alcohols (see 4) with co-production of the phosphine oxide in D2O, -CH(D)OD is formed selectively (36). The mechanism proceeds via a phosphonium species formed by initial nucleophilic attack of the P-atom at the carbonyl C-atom, i.e., via ArCH(OH)P%, where Ar is the aromatic residue and R is the hydroxyalkyl substituent (36). When the aldehyde contains a 4-OH substituent, the alcohol product... 

The Mukaiyama aldol reaction refers to Lewis acid-catalyzed aldol addition reactions of silyl enol ethers, silyl ketene acetals, and similar enolate equivalents,48 Silyl enol ethers are not sufficiently nucleophilic to react directly with aldehydes or ketones. However, Lewis acids cause reaction to occur by coordination at the carbonyl oxygen, activating the carbonyl group to nucleophilic attack. 

The previous sections dealt with reactions in which the new carbon-carbon bond is formed by addition of the nucleophile to a carbonyl group. Another important method for alkylation of carbon nucleophiles involves addition to an electrophilic multiple bond. The electrophilic reaction partner is typically an a,(3-unsaturated ketone, aldehyde, or ester, but other electron-withdrawing substituents such as nitro, cyano, or sulfonyl also activate carbon-carbon double and triple bonds to nucleophilic attack. The reaction is called conjugate addition or the Michael reaction. 

On the basis of these experimental results, a possible mechanism has been proposed for the reaction of 1-215 with Sml2 (Scheme 1.52). After formation of the syn-complex A, a rearrangement occurs to give the aldehyde B, which coordinates to the added aldehyde RCHO to afford complex C. Subsequent samarium-catalyzed nucleophilic attack of the secondary alcohol to the carbonyl of RCHO generates a hemiacetal, D. There follows an irreversible intramolecular 1,5-hydride transfer via... 

Tanaka et al.28 have synthesised a series of (S)-chiral Schiff bases as the highly active (yield 69-99%) and enatioselective (ee 50-96%) catalysts in the reaction of addition of dialkylzinc to aldehydes. The stereochemistry of the asymmetric addition was suggested. In a transition state when S-chiral Schiff base was used as chiral source, the alkyl nucleophile attacked Re face of the activated aldehyde and formed the R-configuration alkylated product [13]. 

Several lupin alkaloids have been derived from the unsaturated quinalozidine 433, that was obtained in the treatment of amine 431 with ortho-quinone 432. This quinone behaves as a model of topaquinone, the cofactor of copper-containing amine oxidases. The cyclization step involved a nucleophilic attack of the piperidine nitrogen of 431 onto a side-chain aldehyde function that is unmasked by the oxidative deamination. Quinolizine 433, when treated with dehydropiperidine, gave the oxime ether 434 that, on ozonolysis followed by reduction, afforded sparteine 10, presumably via the bis(iminium) system 435 (Scheme 102) <1996JOC5581>. 

The pyrirnido[ 1,6-/z [3,l [benzoxazin-1 -thionc 230 was formed in a tandem [5+1, 6+0 (/ )] cyclization as depicted in Scheme 38. The first step is the nucleophilic attack of the aniline nitrogen of 228 (X = O) onto the isothiocyanate and then onto the aldehyde carbon to form l-(2-hydroxymethyl)phenyl-6-hydroxy-tetrahydropyrimidine-2-thione, which cyclizes to 230 <2005BMC3185>. 

The a,( -unsaturated aldehyde 452 is generated from the unstable spiro-oxetane 451, and hydrogen abstraction from the aldehydic C-H bond by 3449 gave a triplet radical pair 453 and 454. Intersystem crossing and radical recombination followed by intramolecular nucleophilic attack of the hydroxyl group toward the ketene functionality furnish the diastereomeric products 54 and 55 (Scheme 102) <20000L2583>. 

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