Enones formylation

In a more elaborate and specific synthesis, the terpenoid indole skeleton found in haplaindole G, which is isolated from a blue-green alga, was constructed by addition of a nucleophilic formyl equivalent to enone 6.5A. Cyelization and aromatization to the indole 6.6B followed Hg -catalysed unmasking of the aldehyde group[6]. 

Another common trapping method is an intramolecular aldol reaction of the initially formed anion, as shown in equation (91) and Schemes 53 and 54.% In the first case, an aldol-like trapping of the iminium salt produced (411 equation 91 ).96b The initial heteronucleophile in the other two cases is ultimately lost from the product by oxidation and elimination, so that the overall process is C—C bond formation at the a-center of an enone. Thus, treatment of the formyl enone (412 Scheme 53) with an aluminum thiolate afforded in 60% yield the trapped product (413) which could be oxidized and eliminated to give (414).96c Addition of the corresponding aluminate species to the ketoacrylate (415 Scheme 54) produced only one diastereomer of the aldol product (416) which was converted into the alkene (417) in excellent yield.96 1... 

Alternatively, the expedient cyanide (or fluoride) ion desilylation of acylsilanes (235), in the presence of a,3-enones or a, 3-unsaturated esters, affords -y-dicarbonyl adducts 182 even bis(trimethylsilyl)ketone (236), a formyl anion equivalent, adds to 2-cyclohexen-l-one to afford 3-formylcyclohexanone in moderate yields.182 ... 

Formylation oft, fl-enones In the presence of HMPT, 2 reacts with cyclic a, fi-enones mainly by 1,4-addition. The adduct can be converted to a hydroxy dimethyl acetal. 

By using the substrates involving both formyl and enone moieties, a tandem reaction of reductive amination Michael addition gives isoindoline derivatives (Equation (26)). 

Benzodithioles 285 (R1 = H) and 7,8-dimethyl-l,5-dihydro-2,4-benzodithiepins286 (R = H) have been used as precursors of formyl and acyl anion derivatives. The lithiation of compounds 285 takes place at —30 °C with n-BuLi and these anions are stable for long periods of time at this temperature454. They react with alkyl iodides, carbonyl compounds and epoxides, the addition to cyclohex-2-enone taking place at the carbonyl group. The deprotection has also been carried out with mercury(II) oxide and BF3 OEt2-... 

Unfortunately, several important classes of a-diazo ketones cannot be prepared in good yield via these standard methods. a -Diazo derivatives of a.p-unsaturated ketones, for example, have previously proved to be particularly difficult to prepare.1113 12 The acylation of diazomethane with a.p-unsaturated acid chlorides and anhydrides is generally not a successful reaction because of the facility of dipolar cycloaddition to conjugated double bonds, which leads in this case to the formation of mixtures of isomeric pyrazolines. Also problematic are diazo transfer reactions involving base-sensitive substrates such as certain a,p-enones and heteroaryl ketones. Finally, the relatively harsh conditions and lack of regioselectivity associated with the thermodynamically controlled Claisen formylation step in the "deformylative" diazo transfer procedure limit the utility of this method when applied to the synthesis of diazo derivatives of many enones and unsymmetrical saturated ketones. 

Benzofuroxan, morpholine and cinnamaldehyde give the mono Af-oxide 5 in 54% yield. Here, the formyl group is removed by the base a similar reaction occurs with benzylideneacetone and with cyclohex-2-enone. The oxidation level of the product is influenced by the base used in the reaction. 

Dondoni et al. have reported the syntheses of KDN (5) and 4-epi-KDN (29) from protected o-mannose (30a, b) (Scheme 3) [86]. The ylid 31, with the thiazole substituent as a masked formyl group, was added to the protected sugars to give the (E)-a,j0-enones 32a, b in good yield. Conjugate addition of benzyl oxide anion to the enones gave mixtures of syn and anti diastereomers... 

A different approach to these enones had earlier been developed by Trost and Jungheim who employed 1-formyl-1-phenylthiocyclopropane as electrophile in aldol reactions with ketone enolates (equation 111). The aldehyde required for this route can be prepared... 

The anion of an aldehyde dithioacetal 5-oxide is well known to add to a,3-unsaturated carbonyl compounds. " Conjugate addition of formaldehyde di-p-tolyl dithioacetal 5-oxide (114) to open-chain and cyclic enones is achieved by using HMPA as a polar cosolvent in THF (-78 C)." The lithio derivative of (5)-(114) was found to add to 2-cyclopentenone with asymmetric induction. Transformation of the dithioacetal part into a formyl group gives 3-formylcyclopentanone in 39% enantiomeric excess (equation 28)." Interestingly, highly asymmetric induction is observed in the conjugate addition of the... 

Reduction of an enone, in preference to a formyl group, with Bu2SnIH was re-... 

Deformylation. The reagent should give good service in synthesis by providing a means for the efficient removal of a protective formyl group. Shimizu, Mitsuhashi, and Caspi" developed an efficient sequence for conversion of (1) into the formyl enone (3) and then needed completing step of deformylation to (5). They found... 

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