Esters, sulfonate from aldehydes

This topological rule readily explained the reaction product 211 (>90% stereoselectivity) of open-chain nitroolefins 209 with open-chain enamines 210. Seebach and Golinski have further pointed out that several condensation reactions can also be rationalized by using this approach (a) cyclopropane formation from olefin and carbene, (b) Wittig reaction with aldehydes yielding cis olefins, (c) trans-dialkyl oxirane from alkylidene triphenylarsane and aldehydes, (d) ketenes and cyclopentadiene 2+2-addition, le) (E)-silyl-nitronate and aldehydes, (f) syn and anti-Li and B-enolates of ketones, esters, amides and aldehydes, (g) Z-allylboranes and aldehydes, (h) E-alkyl-borane or E-allylchromium derivatives and aldehydes, (i) enamine from cyclohexanone and cinnamic aldehyde, (j) E-enamines and E-nitroolefins and finally, (k) enamines from cycloalkanones and styryl sulfone. 

Mulzer (Scheme 8 upper left) obtained the a,/(-unsaturated ester 33 with Z configuration from aldehyde 26a via a Still-Gennari olefination with phosphonate ester 34. Reduction of the ester with DIBAH and application of L-imidazole-PPhj gives allylic iodide 35. This acts as electrophile on the -anion of sulfone 36. After reductive removal of the phenylsulfone, group 28b is obtained [23]. 

From a historical perspective, the a-(dialkylamino)nitrile anions were the first acyl anion equivalents to undergo systematic investigation. More recent studies indicate that anions of a-(dialkylamino)nitriles derived from aliphatic, aromatic or heteroaromatic aldehydes intercept an array of electrophiles including alkyl halides, alkyl sulfonates, epoxides, aldehydes, ketones, acyl chlorides, chloroformates, unsaturated ketones, unsaturated esters and unsaturated nitriles. Aminonitriles are readily prepared and their anions are formed with a variety of bases such as sodium methoxide, KOH in alcohol, NaH, LDA, PhLi, sodium amide, 70% NaOH and potassium amide. Regeneration of the carbonyl group can be achieved... 

Enol phosphates of a-ketosulfones provide the key intermediate to alternate schemes leading to acetylenes. Acylation of phenyl sulfones with esters affords the ketone derivatives directly. Alternately, the ketones can be obtained by Moffat oxidation of the condensation products from aldehydes with sulfone anions. Conversion to the enol derivatives followed by treatment with Na/NH or Na(Hg) gives the acetylenes. 

Initial progress was swift and the two subunits required for the CIO-C16 dithiane fragment, sulfone 12 and aldehyde 10, were easily prepared. Ester 13 was first converted to the mono-protected diol 18 by silylation followed by ester reduction (Scheme 4). The phenyl sulfone auxiliary was next installed in two steps by a Mitsunobu-like thioether formation with diphenyl disulfide and tributylphosphine followed by oxidation with Oxone . The resulting sulfone 19 was desilylated and the liberated hydroxyl group converted to an aldehyde with Swem s procedure. Subunit 12 was completed by formation of the dithiane from aldehyde 20 under standard conditions. 

Insertions into Aldehyde C-H Bonds. The a-diazo ketones (and esters) derived from diazomethane and an acid chloride (or chloroformate) will also insert into the C-H bond of aldehydes to give 1,3-dicarbonyl derivatives. The reaction is catalyzed by SnCL, but some simple Lewis acids, such as BF3 etherate, also work. The reaction works well for ahphatic aldehydes, but gives variable results with aromatic aldehydes, at times giving none of the desired diketone (eq 32). StericaUy hindered aldehydes will also participate in this reaction, as illustratedin eq 33 with the reaction of ethyl a-diazoacetate and pivaldehyde. In a related reaction, a-diazo phosphonates and sulfonates will react with aldehydes in the presence of SnCL to give the corresponding -keto phosphonates and sulfonates. This reaction is a practical alternative to the Arbuzov reaction for the synthesis of these species. 

It was indicated from studies that at the active site of natural enzyme dependent on Vitamin Be, aldehyde group and -amino group of lysine residue could form SchilF base. Under various noncovalent interactions coenzyme is embedded in the enzyme protein. There are three bonds to be dissociated effectively by electron dipping effect of conjugate 4-pyridinyl around or-carbon in the part of amino acid of intermediates at the transition state [22]. On the basis of above, a new transaminase model structure was further developed. Taking AB type sulfonic acid ester generated from m-benzenedisulfochloride and fi-CD as intermediate. 

Other carbanionic groups, such as acetylide ions, and ions derived from a-methylpyridines have also been used as nucleophiles. A particularly useful nucleophile is the methylsulfinyl carbanion (CH3SOCHJ), the conjugate base of DMSO, since the P-keto sulfoxide produced can easily be reduced to a methyl ketone (p. 549). The methylsulfonyl carbanion (CH3SO2CH2 ), the conjugate base of dimethyl sulfone, behaves similarly, and the product can be similarly reduced. Certain carboxylic esters, acyl halides, and DMF acylate 1,3-dithianes (see 10-10. )2008 Qxj(jatjye hydrolysis with NBS or NCS, a-keto aldehydes or a-... 

The key intermediate in these transformations was the hydrazide 83 obtained from the ester 82 by simple treatment with hydrazine hydrate. This intermediate was then transformed by aldehydes, sulfonic chlorides, and isothiocyanates to obtain various aryl hydrazones 84, sulfonylhydrazines 85, and thiocarbazides 86. 

Another important reaction in synthetic chemistry leading to C-C bond formation is the Michael addition. The reaction typically involves a conjugate or nucleophilic 1,4-addition of carbanions to a,/l-unsaturated aldehydes, ketones, esters, nitriles, or sulfones 157) (Scheme 21). A base is used to form the carbanion by abstracting a proton from an activated methylene precursor (donor), which attacks the alkene (acceptor). Strong bases are usually used in this reaction, leading to the formation of byproducts arising from side reactions such as condensations, dimerizations, or rearrangements. 

Further investigation with various silyl ketene acetals is summarized in Table 6. Silyl ketene acetals derived from various esters were reacted with /V-benzyloxy-carbonylamino sulfones 1 in the presence of 0.5-1 mol% Bi(0Tf)3-4H20. The corresponding (3-amino esters 24 were obtained in moderate to good yields (Table 6). Silyl enolates derived from esters as well as thioesters reacted smoothly to give the adducts. The /V - be n z v I o x v c ar bo n v I a m i n o sulfone derived from n-butvraldehyde lp led to moderate yields of (3-amino esters when reacted with (thio)acetate-derived silyl ketene acetals (Table 6, entries 1 and 2). A very good yield was obtained when the same sulfone was subjected to a tetrasubstituted silyl ketene acetal (Table 6, entry 3). The latter afforded moderate to good yields of (3-amino esters 24 with phenylacetaldehyde, / -tolu aldehyde, and o-tolualdehyde-derived sulfones (Table 6, entries 4-6). 

DSM jointly with Du Pont de Nemours308 have patented platinum catalysts generated from the water soluble sulfonated ligand 30 (Table 2 m=0, n=0, m=l, n=2 m=l, n=l, Ar=nBu-S03Li) and used in the aqueous phase hydroformylation of internally unsaturated carboxylic acids, esters or nitriles to their corresponding formyl derivatives which are useful intermediates for the preparation of di-carboxylic acids (e.g. adipic acid). For example, TOFs up to 105 h-1 were achieved in the hydroformylation of 3-pentenoic acid catalysed by Pt/30 (m=0, n=0) at 100°C and 80 bar CO/H2 to give aldehydes with a selectivity of 83% (n/i=3.4), valeric acid (4.6%) and adipic acid (8.1%).308 The products were separated from the aqueous catalyst solution by extraction with ether. Five recycles of the aqueous catalyst solution showed that the Pt/30 (m=0, n=0) catalyst retains its activity. 

The acetaldehyde-sulfurous acid compound has the properties of a sulfonic acid with C-S linkage rather than an ester structure as once assumed. It is properly 1-hydroxyethane sulfonic acid (23, 24) and is highly acidic (25). Samples of concentrated heads from commercial aldehyde columns having aldehyde contents of 5-13% gave pH values of 0.7-0.9 and contained high levels of copper (25). 

Carbonyl compounds from sulfones.2 a-Sulfonyl carbanions react with 1 to form a-sulfonyl boronic esters, which are oxidized to aldehydes or ketones by m-chloroperbenzoic acid or sodium m-chloroperbenzoate (C1C6H4C03H -I- NaH in CH2C12, -60°). 

A large part of the usefulness of the Michael reaction in organic synthesis derives from the fact that almost any activated alkene can serve as an acceptor7—a, 3-unsaturated ketones, esters, aldehydes, amides, acids, lactones, nitriles, sulfoxides, sulfones, nitro compounds, phosphonates, phosphoranes, quinones,... 

The at complex from DIB AH and butyllithium is a selective reducing agent.16 It is used tor the 1,2-reduction of acyclic and cyclic enones. Esters and lactones are reduced at room temperature to alcohols, and at -78 C to alcohols and aldehydes. Acid chlorides are rapidly reduced with excess reagent at -78 C to alcohols, but a mixture of alcohols, aldehydes, and acid chlorides results from use of an equimolar amount of reagent at -78 C. Acid anhydrides are reduced at -78 C to alcohols and carboxylic acids. Carboxylic acids and both primary and secondary amides are inert at room temperature, whereas tertiary amides (as in the present case) are reduced between 0 C and room temperature to aldehydes. The at complex rapidly reduces primary alkyl, benzylic, and allylic bromides, while tertiary alkyl and aryl halides are inert. Epoxides are reduced exclusively to the more highly substituted alcohols. Disulfides lead to thiols, but both sulfoxides and sulfones are inert. Moreover, this at complex from DIBAH and butyllithium is able to reduce ketones selectively in the presence of esters. 

Organic chemicals that are susceptible to oxidation and are of concern from the perspective of contamination and environmental degradation include aliphatic and aromatic hydrocarbons, alcohols, aldehydes, and ketones phenols, polyphenols, and hydroquinones sulfides (thiols) and sulfoxides nitriles, amines, and diamines nitrogen and sulfur heterocyclic compounds mono- and di-halogenated aliphatics linear alkybenzene-sulfonate and nonylphenol polyethoxylate surfactants and thiophosphate esters. Table... 

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