Carbonyl compounds alkylidenation

We have just seen in a preceding scheme (see Section 4.2.1.5) an example of alkylation of a silylated enolate with phenylthiomethyl chloride. The Lewis acid-promoted phenylthioalkylation of O-silylated enolates of ketones, aldehydes, esters and lactones has been used by Paterson and Fleming as a convenient synthetic route to a-alkylated or alkylidenated carbonyl compounds [323-325] according to the accompanying scheme. 

Subsequent to Hantzsch s communication for the construction of pyridine derivatives, a number of other groups have reported their efforts towards the synthesis of the pyridine heterocyclic framework. Initially, the protocol was modified by Beyer and later by Knoevenagel to allow preparation of unsymmetrical 1,4-dihydropyridines by condensation of an alkylidene or arylidene P-dicarbonyl compound with a P-amino-a,P-unsaturated carbonyl compound. Following these initial reports, additional modifications were communicated and since these other methods fall under the condensation approach, they will be presented as variations, although each of them has attained the status of named reaction . 

BalLini and coworkers have developed a new strategy for alkenyladon of carbonyl compounds based on the Michael adthdon followed by eliminadon of HNO fsee Secdon 7 3 A variety of 2-alkylidene 1,4-tholes have been conveniently prepared, in two steps, by the Michael adthdon of a nltroalkane to the appropriate enedione derivadves under basic conthdons, followed by chemoselecdve reducdon v/ith LLAlHl CEq 4 123 ... 

The simultaneous protection of two hydroxyl groups by condensation of sugars with carbonyl compounds to give 1,3-dioxolanes or 1,3-dioxanes is also applicable to D-glucuronic acid. Principally, for the preparation of O-alkylidene-a-D-glucofuranuronic acid derivatives, two methods are available 1, direct condensation of 2 or 4 with... 

The isomerization of a-alkylidene cyclic carbonyl compounds to a,/3-unsaturated cyclic carbonyl compounds was achieved by using catalytic amounts of RhCl(PPh3)3 and Et3SiH (Scheme 48).87... 

As noted above, titanocene-alkylidenes can be prepared using various methods and starting materials. Like the methylidene complex, higher alkylidene complexes are useful for the transformation of carbonyl compounds to highly substituted olefins. Ketones and aldehydes are converted into substituted allenes by treatment with titanocene-alkenylidenes prepared by olefin metathesis between titanocene-methylidene and substituted allenes (see Scheme 14.7) [17]. Titanocene-alkenylidene complexes can also be prepared from... 

Titanium-based reagents generated by the reduction of gem-dihalides with low-valent metal species are widely used for the alkylidenation of carbonyl compounds (Scheme 14.28). As in the case of methylidenation, the system gem-dibromide/TiCl4/Zn/TMEDA... 

Other Carbonyl Compounds. The reaction of alkylidenetriphenylphosphoranes with lactones (Scheme 8) affords betaines (32), which can be thermally decomposed to eliminate triphenylphosphine, giving lactones in which the alkylidene grouping of the starting ylide is incorporated into the ring.34... 

The above-described desulphonylation, combined with the previously described selective reduction of a, -unsaturated carbonyl compounds, can be applied to a-alkylidene... 

Alkylidenation of aldehydes and cyclopropanation of o jS-unsatu-rated carbonyl compounds with dibromomalonic esters... 

Simple addition to carbonyl compounds occnrs nnder mild acidic conditions. Examples given illns-trate reaction with acetone, an aldol-like reaction, and conjngate addition to methyl vinyl ketone, a Michael-like reaction. The first-formed alcohol products in aldol-like reactions usually dehydrate to give a 3-alkylidene-3//-indolium cation. 

The ring opening of tetrahydro-l,3-oxazines to aldehydes has recently found wide application through the work of Meyers.2-3 2-Alkylidene-tetrahydro-l,3-oxazines, prepared from the readily available 5,6-dihydro-4//-1,3-oxazines, possess strong nucleophilic properties and can react with alkyl halides and carbonyl compounds. The derivatives so obtained can be reduced to tetrahydro-l,3-oxazines, and through ring opening the latter can furnish acyclic, alicyclic, and a,jS-unsaturated aldehydes and their C-l deuterated derivatives.221-223 228... 

Alkylidene carbonyl iridium complexes, reactions, 7, 275 Alkylidene compounds, NLO properties, 12, 121 Alkylidene-containing complexes, in molybdenum complexes, Schrock-type complexes, 5, 524 a-Alkylidene cyclic carbonyl compounds, isomerization,... 

In the synthesis of specially substituted methylene diphosphines, made from secondary phosphines and carbonyl derivatives (7), a carbenium ion adjacent to trivalent phosphorus as the transition state has been discussed. The transfer of this reaction principle to primary phosphines and suitable carbonyl compound revealed a further pathway to derivatives of dicoordinated phosphorus (8). Aromatic phosphines react with carboxylic acid amide acetals under elimination of alcohol giving dialkylamino-alkylidene phosphines (Scheme 5). A modification of the synthesis... 

In this section, consideration will be given to the actual processes of acetal- or ketal-formation and not to the more indirect methods by which acetals and ketals of the polyhydric alcohols may be synthesized from compounds (e.g. derivatives of the monosaccharides) containing preformed alkylidene or arylidene groupings. The condensation of a carbonyl compound with a glycol is facilitated by acidic catalysts, and, since the reaction is reversible, by dehydration. The catalysts most frequently employed are concentrated sulfuric, hydrochloric and hydro-bromic acids, gaseous hydrogen chloride, zinc chloride and cupric sulfate others are phosphorus pentoxide, sulfosalicylic acid, and anhydrous sodium sulfate. The formation of benzylidene compounds is promoted less efficiently by phosphorus pentoxide than by either concentrated sulfuric acid or concentrated hydrochloric acid 1" the reaction is assisted by chloro- and nitro-substituents on the aromatic nucleus, but hindered by methyl- and methoxy-groups.18... 

A major problem in the reaction of a,/3-unsaturated carbonyl compounds and alkenes proves to be the competition between hetero Diels-Alder and ene reactions. Intramolecular cycloadditions of 1,6- and 1,7-dienes with ester and cyano groups at the double bond yield the ene product nearly exclusively, but with alkylidene- and benzylidene-ketoesters and 1,3-diketones the Diels-Alder reaction is preferred under thermal conditions, however under Lewis acid catalysis also ene reactions occur [12]. 

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