Formyl anions

The anion of A-nitromethyIphthalimide 17 also acts as a formyl anion equivalent with Michael acceptors to afford 1,4-dicarbonyl compounds 18 in good to excellent yields, although difficulty was experienced in isolating the products under the conditions required for removal of the phthalimide group (77CJC2919). 

A somewhat similar method to that mentioned above involves alkylation of 4,4-dimethyl-1,3-oxathiolane 5,5-dioxide 32 at the 2 position followed by FVP at 400°C, which results in fragmentation with loss of SO2 and isobutene to give the aldehydes 33. Other electrophiles that may be used include aldehydes, ketones, and McsSiCl, making this a convenient formyl anion equivalent (79TL3375). 

More recent work has shown that the 2-unsubstituted compound 40 (R = H, R = Pr ) is an effective formyl anion equivalent which reacts at C2 and undergoes both 1,4-addition to a,(3-unsaturated carbonyl compounds and 1,2-addition to aldehydes (93TL3907 96T4719). 

A variety of 1,3-oxazolidines have been used as chiral formyl anion equivalents for addition to aldehydes. Thus, for example, reaction of N-protected norephedrine with Bu3Sn-CH(OEt)2 gives 48, and transmetallation with BuLi followed by addition of benzaldehyde affords the expected adduct 49. The selectivity at the newly formed alcohol center is poor, but the situation can be salvaged by oxidation and re-reduction, which affords the product 50 with >95% d.e. It is then a simple matter to hydrolyze off the oxazolidine, although the resulting hydroxyaldehydes... 

The foregoing examples do not represent useful chiral formyl anion equivalents in a direct sense since the stereoselectivity of the initial addition to aldehydes is poor, although as has been explained, the situation is salvaged by oxidation and re-reduction. On the other hand, by lithiation at the 2 position of the achiral oxazo-lidine 53 in the presence of (-)-sparteine followed by addition of benzaldehyde, useful levels of d.e. and e.e. are achieved directly (98TA3125). For example, by adding MgBr2 before the benzaldehyde, the major product obtained is 54 in 80% d.e. and 86% e.e. 

The chiral bicyclic imidazolidine 74 is deprotonated at the 2 position by s-BuLi and the resulting anion adds to alkyl halides, acid chlorides, chlorofor-mates, phenyl isocyanate, and aldehydes. The use of this compound as a chiral formyl anion equivalent seems to be limited, however, since the diastereoselectiv-ity in the addition to aldehydes is poor and hydrolysis of the products 75 to give aldehydes also produces cyclohexane-1,2-diamine, necessitating isolation of the aldehyde as its 2,4-dinitrophenylhydrazone (96SL1109 98T14255). 

The triazole 76, which is more accurately portrayed as the nucleophilic carbene structure 76a, acts as a formyl anion equivalent by reaction with alkyl halides and subsequent reductive cleavage to give aldehydes as shown (75TL1889). The benzoin reaction may be considered as resulting in the net addition of a benzoyl anion to a benzaldehyde, and the chiral triazolium salt 77 has been reported to be an efficient asymmetric catalyst for this, giving the products (/ )-ArCH(OH)COAr, in up to 86% e.e. (96HCA1217). In the closely related intramolecular Stetter reaction e.e.s of up to 74% were obtained (96HCA1899). 

Pyridinium p-toluenesulfonylmethylide 91 has been used as a formyl anion equivalent for conjugate addition to N-substituted maleimides to give the enol ethers 92, which were readily deprotected to give the aldehydes 93 (80TL705). 

The (V-methyldihydrodithiazine 125 has also been used as an effective formyl anion equivalent for reaction with alkyl halides, aldehydes, and ketones (77JOC393). In this case there is exclusive alkylation between the two sulfur atoms, and hydrolysis to give the aldehyde products is considerably easier than for dithianes. However, attempts to achieve a second alkylation at C2 were unsuccessful, thus ruling out the use of this system as an acyl anion equivalent for synthesis of ketones. Despite this limitation, the compound has found some use in synthesis (82TL4995). 

In contrast to this, the monosulfoxide 132, readily prepared from 129 by oxidation, acts as a highly diastereoselective formyl anion equivalent and adds to... 

Professor D Auria (Basilicata University) summarizes the photochemical isomerization of pentaatomic heterocycles, providing a unified description in terms of the five conceivable mechanisms. R. Alan Aitken and Andrew W. Thomas of the University of St. Andrews, Scotland, summarize the substantial recent progress in heterocyclic acyl and formyl anion equivalents. 

The Michael addition of nitromethane to cyclopentenone derivatives is used for synthesis of prostaglandins (Scheme 4.20).158 Here, the anion of nitromethane is used as a formyl anion synthon. 

Deprotection of 2,2-disubstituted-l,3-dithiolanes to give carbonyl compounds can be achieved using Oxone with KBr in aq. MeCN <06TL8559> and a review of silylated heterocycles as formyl anion equivalents includes reference to 64 <06CC4881>. A method for transformation of propargylic dithiolanes 43 into tetrasubstituted furans has been reported <06SL1209> and Michael addition of enolates to the chiral dithiolane dioxide 65 takes place... 

Phenylthio-l-trimethylsilylalkanes are easily prepared by the alkylation of (phenylthioXtrimethylsilyl)mcthane as shown in Scheme 10 [40], The treatment of (phenylthio)(trimethylsilyl)methane with butyllithium/tetramethylethylene-diamine (TMEDA) in hexane followed by the addition of alkyl halides or epoxides produces alkylation products which can be oxidized electrochemically to yield the acetals. Since acetals are readily hydrolyzed to aldehydes, (phenylthioXtrimethylsilyl)methane provides a synthon of the formyl anion. This is an alternative to the oxidative transformation of a-thiosilanes to aldehydes via Sila-Pummerer rearrangement under application of MCPBA as oxidant [40, 41]. 

The base-catalysed addition of thiols to Jt-electron-deficient alkenes is an important aspect of synthetic organic chemistry. Particular use of Triton-B, in place of inorganic bases, has been made in the reaction of both aryl and alkyl thiols with 1-acyloxy-l-cyanoethene, which behaves as a formyl anion equivalent in the reaction [1], Tetra-n-butylammonium and benzyltriethylammonium fluoride also catalyse the Michael-type addition of thiols to a,P-unsaturated carbonyl compounds [2], The reaction is usually conducted under homogeneous conditions in telrahydrofuran, 1,2-dimethoxyethane, acetone, or acetonitrile, to produce the thioethers in almost quantitative yields (Table 4.22). Use has also been made of polymer-supported qua-... 

Although various compounds are known to act as synthetic equivalents to the formyl anion synthon,12 the advantages that appear to be associated with the use of 2-TST warrant comment. First, 2-TST is a readily available, relatively cheap, and storable reagent second, it reacts promptly and stereoselectively with aldehydes under neutral conditions third, it gives high yields of products that are stable to isolation and purification and nevertheless can be readily transformed into aldehydes. 

Dondoni pioneered the use of 2-(trimethylsilyl)thiazole (71) as a formyl anion equivalent for the homologation of aldehydes. Extension of this reaction to ketones would be very useful, but has thus far been restricted to tritluoromethyl cases. However, it has now been widened to include several a, a -alkoxy ketones, as demonstrated in a new route to branched-chain monosaccharides. Aldehydes catalyse the reaction, although the scope is still limited electrophilic aldehydes, such as 2-fluorobenzaldehyde, promote the addition of (71) to electrophilic ketones. 

The utility of -phenyl camphor-derived oxazolidinones as chiral formyl anion syn-thons has been demonstrated by Gawley and coworkers (Scheme 42). Deprotonation yields a dipole-stabihzed organolithium intermediate and the absolute configuration of the lithium-bearing carbon is presumed to be R. Additions to benzaldehyde and cyclohexane carboxaldehyde are 86% and 76% diastereoselective, respectively, but recrystallization affords a single diastereomer in the yields shown. Addition is postulated to proceed via the pre-complex shown in the inset, in which the aldehyde is coordinated to the R epimer... 

The behavior of 2-substituted- or 2-unsubstituted-5(4//)-oxazolones is completely different. Reaction of electrophiles with 2-substimted-5(47/)-oxazolones usually occurs at C-4, whereas reaction of electrophiles with 2-unsubstituted-5(47/)-oxazolones affords the corresponding 5(2//)-oxazolones. The best example of the behavior of 2-unsubstituted-5(47/)-oxazolones involves 4-isopropyl-5(47/)-oxazolone 143, the anion of which can be considered as a formyl anion equiva-lent. ° ° Thus, reaction of 143 with a catalytic amount of triethylamine gives 144 that reacts with a,p-unsaturated carbonyl compounds to afford Michael adducts or with aldehydes to produce the corresponding aldol adducts. Mild acid hydrolysis of 145 yields the corresponding aldehydes (Scheme 7.42). 

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