Lactones from enals

Homoenolate Reactivity The ability to generate homoenolates from enals and its application to the preparation of y-butyrolactones 30, through reaction with an aldehyde or aryl trifluoromethyl ketone, was reported independently by Glorius [8], and Bode and Burstein [9] (Scheme 12.4). A sterically demanding NHC catalyst is required to promote reactivity at the d terminus and to prevent competitive benzoin dimerisation. Nair and co-workers have reported a similar spiro-y-lactone formation reaction using cyclic 1,2-diones, including cyclohexane-1,2-dione and substituted isatin derivatives [10]. 

Scheldt and co-workers have also accessed enolate equivalents from enals to furnish cyclopentanes 236 asymmetrically. Formation of the enolate equivalent from enals 235 with the NHC, followed by an intramolecular Michael reaction and 0-acylation, gives the lactone products 236, which are readily opened by either alcohols or amines to generate functionalised cyclopentane derivatives 237 in excellent ee. 

NHC-promoted enolate formation from an enal, followed by a desymmetrising aldol event to generate P-lactones and loss of CO, has been exploited by Scheidt and co-workers to generate functionalised cyclopentenes 240 in high ee from enal substrates 238 (Scheme 12.52) [94]. Interestingly, the use of alkyl ketones in this reaction manifold allows the isolation of the p-lactone intermediates with acyclic diketones, P-lactones 239 are formed with the R group anti- to the tertiary alkox-ide, while with cyclic diketones the P-lactone products have the R group with a syn relationship to the alkoxide [95]. 

The epoxide 70, derived from D-mannitol, has been converted into the 6-lactone 71 via the key intermediates shown in Scheme 15. This compound is the dihydro-derivative of (H-)-boranolide, the corresponding a,P-unsaturated lactone, and this work constitutes a formal synthesis of the natural product. The enal 72, derived from tri-O-acetyl-D-glucal, has been converted in a multistep process into the unsaturated lactone 73, an analogue of the a,p-unsaturated lactone portion of a number of natural products. ... 

The ability of A -heterocyclic carbenes to activate a,p-unsaturated carbonyl compounds via the formation of the corresponding Breslow intermediate, which plays the role of a homoenolate nucleophile, has also been applied to a cascade process involving a formal intramolecular Michael reaction/oxidation/ lactonization, leading to the formation of complex tricyclic carbon frameworks starting from a bifunctional substrate containing an enone and an a,p-unsa-turated aldehyde side chain linked to each other via a benzene tether (Scheme 7.82). The reaction involved a complex multistep mechanism which started with the activation of the enal by the catalyst, forming the Breslow intermediate, which subsequently underwent intramolecular Michael reaction and next the generated enol-type intermediate reacted intramolecularly with the... 

The Scheidt group reported a highly enantioselective NHC-catalyzed addition of a,p-unsaturated aldehydes to isatins activated by lithium cations (up to 93% yield, >20 1 dr, 97% ee). The addition of lithium chloride as a Lewis acid with p-aryl substituted enals generates lactone products with high enantioselectivity (up to 93% ee) which result from an organized transition... 

In 2006, Nair disclosed the synthesis of ( )-tra s-l,3,4-trisubstituted cyclopentenes resulting from the addition of enals to chalcones catalysed by an achiral carbene." " Mechanistically, the addition of the generated homo-enol to enones to give adduct II, followed by intramolecular acylation to afford cyclopentane-fused p-lactone IV. The final cyclopentene 67 was formed by the in situ decarboxylation of the p-lactones (Scheme 20.32). The enantioselective variant of the process to access ds-cyclopentenes was reported by Bode et al. in 2007. ... 

Raw or gently pasteurised milk (e.g. for 10 seconds at 73 °C) has a fine characteristic odour and sweet taste. Typical components present in low concentrations are dimethylsulfide, biacetyl, 2-methylbutan-l-ol, (Z)-hept-4-enal and ( )-non-2-enal. Milk pasteurised at higher temperatures and Ultra High Temperature (UHT) milk present the so-called cooked flavour, the appearance of which is the first measurable manifestation of the chemical changes that occur in heated milk. The substances responsible for the cooked off-flavour are sulfane and other sulfur compounds. Of particular importance are dimethylsulfide, dimethyldisulfide and dimethyltrisullide that are produced from proteins contained in the membranes of fat particles and from thiamine. Also relevant are alkane-2-ones (methylketones) generated by thermal decarboxylation of P-oxocarboxylic acids (mainly hexane-2-one, heptane-2-one and nonane-2-one), y-lactones and 5-lactones produced by dehydration of y- and 5-hydroxycarboxylic acids (mainly 8-decalactone and y- and 8-dodecalactones). Important carbonyl compounds include biacetyl, hexanal, 3-methylbutanal, (Z)-hept-4-enal and ( )-non-2-enal. In the more intensive thermal treatment of milk (sterilisation), products of the Maillard reaction play a role, such as maltol and isomaltol, 5-hydroxymethylfuran-2-carbaldehyde, 4-hydroxy-2,5-dimethyl-2 f-furan-3-one (furaneol) and 2,5-dimethylpyrazine. 

The aroma of butter made from sweet cream is affected primarily by free fatty acids (especially capric and lauric acids), S- and y-lactones, dimethylsulfide, (Z)-hept-4-enal and the degradation products of tryptophan (indole and skatole). The butter obtained from sour cream contains mainly metabolic products of microorganisms (so-called starter cultures). Especially important compounds are biacetyl, lactic and acetic acids. 

All possible stereoisomers of -4,5-dihydroxydec-2-enal 333 have been prepared from D- and L-arabinose, D-ribose and L-lyxose. Key reactions involve Cl Wittig homologation, reduction and C4,C5 oxidative cleavage. The eneyne 336, an intermediate for a synthesis of la,2S-dihydroxyvitamin D3, has been prepared from D-xylose via lactone 334 and 335. Lithioacetylene used for alkyne introduction and further elaboration provides 336 (Scheme 51). ... 

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