Reactions enals

Thermal cycli2alion of dienones enals, ynones, diones keloesters, etc, to monocyclic spirocycfc bicyclic derivatives, (ene reaction of unsalurated enol)... 

From a mechanistic standpoint, ammonia serves two functions 1) it behaves as a base to catalyze an aldol reaction between 2 equivalents of 31 to generate the corresponding enal 33, and 2) it is the source of nitrogen for the resultant pyridyl ring. This occurs through formation of enamine 34 with a third equivalent of 31. The Michael addition of 34 to 33 followed by cyclization gives rise to 32. 

Only two operations remain. Reaction of the enolic form of aldehyde 162 with Eschenmoser s reagent (H2C=NMe2+I-)62 in the presence of triethylamine provides the desired enal after a simple / -elimination. Finally, cleavage of the remaining tcrt-butyldi-methylsilyl ether with HF pyridine completes the total synthesis of (+)-brevetoxin B (1). 

Olefin cross metathesis starts to compete with traditional C=C bondforming reactions such as the Wittig reaction and its modifications, as illustrated by the increasing use of electron-deficient conjugated alkenes for the ( )-selective construction of enals and enoates. 

An endo-selective ionic Diels-Alder reaction of a,/f-enone and a,/f-enal acetals catalyzed by electrogenerated acid [99]... 

Lopez J. C., Lukacs G. Pyranose-Derived Dienes and Conjugated Enals. Preparation and Diels-Alder Cycloaddition Reactions ACS Symp. Ser. 1992 494 33-49 Keywords carbohydrate, befera-Diels-Alder reactions, stereoselectivity... 

An oxygen analogue, 2,4,6-trimethylpyrilium (51) perchlorate, is also found to undergo a photoinduced hydration reaction, to give experimental data that this is the only, or even the preferred reaction route. 

Fig. 13 Diels-Alder reactions with enals catalyzed by 24...

Fig. 15 [3 + 2] cycloaddition reactions of diarylnitrones with enals catalyzed by 29a... 

Viton F, Bemardinelli G, Kiindig EP (2002) Iron and ruthenium Lewis acid catalyzed asymmetric 1,3-dipolar cycloaddition reactions between nitrones and enals. J Am Chem Soc 124 4968-4969... 

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]. 

Bode and co-workers have used NHCs to form y-butyrolactams 34 from enals 27 and saccharin-derived cyclic sulfonylimines 32. A range of [3-alkyl and [3-aryl substituted enals, and a variety of substituted imines, are tolerated in this reaction,... 

Scheme 12.8 Redox reaction of enals to give saturated esters...

This homoenolate methodology has been extended to the use of nitrones 170 as electrophiles [72]. Scheldt and co-workers have shown that enantiomerically enriched y-amino esters 172 can be prepared with excellent levels of stereocontrol from an enal 27 and a nitrone 170 using the NHC derived from triazolium salt 164 (Scheme 12.37). The oxazinone product 171, formally a result of a [3-1-3] cycloaddition, is cleaved to afford the y-amino ester product 172. The reaction shows broad substrate scope, as a range of substituted aryl nitrones containing electron donating and withdrawing substituents are tolerated, while the enal component is tolerant of both alkyl and aryl substituents. 

A formal [3h-2] cycloaddition reaction with homoenolates has also been realised with nitrogen-based electrophiles such as A-acyl-A -aryldiazenes 180. Pyrazolidi-nones 178 can be prepared from enals 27 and acyldiazenes 180, as demonstrated by Scheldt and Chan [75]. An example of the asymmetric variant demonstrates excellent levels of enantioselectivity in this reaction (90% ee) (Scheme 12.39). 

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. 

This reaction is equally amenable to enals with both aliphatic and aromatic P-substituents, althongh the formation of substitnted cyclohexanes (from analogous enals) proceeds with rednced enantioselectivity (Scheme 12.51) [92], You and co-workers have shown that the same reaction is also promoted by triazolinm salts derived from camphor in excellent enantioselectivity (95-99% ee) [93]). 

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]. 

---