Aldehydes generation

The simplest and most direct manner to generate acyl anion equivalents is through reaction of an NHC with an aldehyde, generating an enamine species 8, commonly referred to as a Breslow intermediate . Subsequent reaction with an electrophile, classically using aldehydes or enones, generates the benzoin and Stetter products 10 and 11 respectively (Scheme 12.1). 

The enantioselective synthesis in Scheme 13.22 is based on stereoselective reduction of an a, (3-unsaturated aldehyde generated from (—)-(.V)-limonene (Step A). The reduction was done by Baker s yeast and was completely enantioselective. The diastereoselectivity was not complete, generating an 80 20 mixture, but the diastere-omeric alcohols were purified at this stage. After oxidation to the aldehyde, the remainder of the side chain was introduced by a Grignard addition. The ester function... 

Addition of A-mesityl benzimidazolyl carbene 720 to an a,/3-unsaturated aldehyde generates a homoenolate intermediate that undergoes an addition/acylation sequence with azomethine imine 719 to afford (3R, 5S, 6S )-177-pyrazolo[l,2- ]pyridazine-l,8(5//)-diones 721 with excellent diastereoselectivity. Compound 721 (Ar = R = Ph) treated with sodium hydoxide in methanol or benzylamine provided nearly quantitatively, ring-opened products 722a and 722b, respectively (Scheme 116) <2007JA5334>. 

Knoevenagel condensation of 1 2.1 stoichiometric ratio of the pyran and aldehyde generates a pure bis-condensation product. Due to the extended ir-conjugated system, these bis-condensed red emitters are about 40-50 nm red-shifted compared with their respective mono-substituted DCM analogues. 

There are virtually no drugs that are aldehydes but there are dietary aldehydes, and aldehydes are common metabolites of drugs including the aldehydes generated as intermediates in monoamine oxidase (MAO)-catalyzed deamination reactions, P450-catalyzed... 

The reaction < —40 °C of svw-vinyl substituted acyclic (/p-allyljlVKCOjjCp complexes 57 (M = Mo, W Cp = Cp, Cp ) with CF3CO2H or a mixture of BF3 and an aldehyde generates the s-trans (diene)M(CO)2Cp/ cations 58a or 58b respectively, which may be isolated by precipitation from ether (Scheme 15)30,88. At higher temperature... 

Breslow and co-workers elucidated the currently accepted mechanism of the benzoin reaction in 1958 using thiamin 8. The mechanism is closely related to Lapworth s mechanism for cyanide anion catalyzed benzoin reaction (Scheme 2) [28, 29], The carbene, formed in situ by deprotonation of the corresponding thiazolium salt, undergoes nucleophilic addition to the aldehyde. A subsequent proton transfer generates a nucleophilic acyl anion equivalent known as the Breslow intermediate IX. Subsequent attack of the acyl anion equivalent into another molecule of aldehyde generates a new carbon - carbon bond XI. A proton transfer forms tetrahedral intermediate XII, allowing for collapse to produce the a-hydroxy ketone accompanied by liberation of the active catalyst. As with the cyanide catalyzed benzoin reaction, the thiazolylidene catalyzed benzoin reaction is reversible [30]. 

Preliminary mechanistic studies show no polymerization of the unsaturated aldehydes under Cinchona alkaloid catalysis, thereby indicating that the chiral tertiary amine catalyst does not act as a nucleophilic promoter, similar to Baylis-Hilhnan type reactions (Scheme 1). Rather, the quinuclidine nitrogen acts in a Brpnsted basic deprotonation-activation of various cychc and acyclic 1,3-dicarbonyl donors. The conjugate addition of the 1,3-dicarbonyl donors to a,(3-unsaturated aldehydes generated substrates with aU-carbon quaternary centers in excellent yields and stereoselectivities (Scheme 2) Utility of these aU-carbon quaternary adducts was demonstrated in the seven-step synthesis of (H-)-tanikolide 14, an antifungal metabolite. 

PPhsP = CHR, with the aza-analogue PPhaP = NR (Scheme 5). The condensation of the aldehyde, generated in situ , with PPhsP = NR gives the imine, which was hydrogenated to the amine. 

A related process, from this conceptual point of view (Eq. 16), the use of the aldehyde generated in situ for further reactions, has allowed the a-alkylation of ketones with primary alcohols [62], Several ketones have been condensed with 1-butanol or benzyl alcohol affording the corresponding a-alkylated ketones in good yields (up to 96%) in the presence of [ lr(/z-Cl)(cod) 2] andKOH. 

Auto-tandem hydroformylation-cyclization, catalyzed by [RhCl(cod)]2, enables expansion of the organic skeleton of unsaturated silyl enol ethers (Scheme 10). Linear aldehydes generated in the hydroformylation step subsequently undergo Rh-catalyzed, intramolecular Mukaiyama aldol addition. Bicyclic ketones are also accessible from cyclic silyl enol ethers. 

An alternative access was achieved by alkylation of the a-diphenylphosphino acetaldehyde SAMP hydrazone 95, yielding the hydrazone products 96 in good yields (60-63%) and good diastereomeric excesses (die = 68-71%) as EjZ mixtures, from which the major diastereomer was separated and purified by preparative HPLC. Ozonolysis and in-situ reduction with the borane-dimethyl sulfide complex of the aldehydes generated gave the air-stable borane-protected 2-diphenylphosphino alcohols 97 in good yields (67-83%). Reaction with DABCO afforded the unprotected 2-phosphino alcohols 98 in very good yields (85-91%) and excellent enantiomeric excesses (ee > 96%) (Scheme 1.1.27). 

Dithiobiurets react with a-halo ketones79-82 or aldehydes (generated in situ)63 to yield 2-thiureidothiazoles (40), which can be converted in two steps to 2-guanidinothiazoles.81 However, Beyer and Hantschel81 found that 2-guanidinothiazoles could be more conveniently prepared via the reaction of 1-amidino-2-thiourea with a-halo ketones or aldehydes. 

Both stoichiometric and catalytic reactions of allylic compounds via 7r-allyl complexes are known. Reactions of nucleophilic 71-allyl complexes with electrophiles involve oxidation of metals and hence constitutes stoichiometric reactions. 7i-Allyl complexes of Ni, Fe, Mo, Co and others are nucleophilic and undergo the stoichiometric reaction with electrophiles. However, electrophilic 71-allyl complexes react with nucleophiles, accompanying reduction of metals. For example, 71-allylnickel chloride (2) reacts with electrophiles such as aldehydes, generating Ni(II), and hence the reaction is stoichiometric. In contrast, electrophilic 7i-allylpalladium chloride (3) reacts with nucleophiles such as malonate and Pd(0) is generated. Thus repeated oxidative addition of allylic compounds to Pd(0) constitutes a catalytic reaction. 

The aluminium alkoxide acts as a Lewis acid to coordinate with one molecule of the aldehyde, and to facilitate the addition of a second equivalent of aldehyde, generating a hemiacetal intermediate ... 

As opposed to ketones, the same low-temperature action of sulfur and ammonia on aldehydes received very little attention presumably because the results of the initial exploration discouraged utilization in synthetic chemistry. Again in reference to unpublished work, the product mixture was claimed to contain 3-thiazoline, formed in 10% yield (3). The low-temperature synthesis of aldehyde-generated thiazolines (2, Rj = R2 = H), as depicted in Figure 1, possibly may have some geochemical interest when viewed in the Tight of reports that such thiazolines are dehydrogenated to thiazoles by sulfur at 130 6C ( -10). 

The C-7 side chain is introduced by addition of a Grignard reagent to the aldehyde generated from the primary hydroxyl function by oxidation, and subsequent Dess-Martin oxidation. The total synthesis is completed by conversion of the silyl-substituted furan into the maleic anhydride. The masked anhydride is liberated by successive photooxidation and further oxidation of the intermediate lactol with PCC [6a]. 

In 1872 von Baeyer reported that the reaction between pyrroles and aldehydes generated cyclic compounds, now known as calixpyrroles by analogy to the calixarenes, and also that the reaction of resorcinol and range of aldehydes formed cyclote-tramers, now known as resorcinarenes, shown in Fig. 1.11. Calixpyrroles have been of considerable interest of late as they are able to bind anions, with a particular preference for fluoride [43],... 

The aldehyde generated by this first disconnection is also a, p-unsaturated, so we can do another a,p disconnection, back to a ketone whose synthesis we have already discussed (p. 787). 

Enantioselective organocatalytic (with tetrahydro-4//-imidazol-4-one-based catalysts of type 102nHX) 2-alkylation of pyrroles by, -unsaturated aldehydes generates 3-(pyrrol-2-yl) aldehydes 103 (Scheme 46) <2001JA4370, 2002JA1172, 200SJA1S0S1 and references therein>. 

A convenient synthesis [Eq. (13)] of 2-ary lidenehydrazono-4-thia-zolidinone (43) from ethyl thiocyanoacetate (44), arylideneazines (45), and hydrazine hydrate (46) has been reported.79 Presumably, the reaction proceeds via the intermediary hydrazone, which condenses with 44 to give 43. Subsequently, condensation of 43 with the aromatic aldehyde, generated in situ from disproportionation of the azine with hydrazine, affords the 5-arylidene derivative. The reaction of 44 with ammonium acetate and an aromatic aldehyde gives 5-arylidene-2-imino-4-thiazolidinones.80... 

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