Keto nitriles ketones

The Michael reaction occurs with a variety of a,/3-unsaturated carbonyl compounds, not just conjugated ketones. Unsaturated aldehydes, esters, thio-esters, nitriles, amides, and nitro compounds can all act as the electrophilic acceptor component in Michael reactions (Table 23.1). Similarly, a variety of different donors can be used, including /3-diketones, /3-keto esters, malonic esters, /3-keto nitriles, and nitro compounds. 

Acid derivatives that can be converted to amides include thiol acids (RCOSH), thiol esters (RCOSR), ° acyloxyboranes [RCOB(OR )2]. silicic esters [(RCOO)4Si], 1,1,1-trihalo ketones (RCOCXa), a-keto nitriles, acyl azides, and non-enolizable ketones (see the Haller-Bauer reaction 12-31). A polymer-bound acyl derivative was converted to an amide using tributylvinyl tin, trifluoroacetic acid, AsPh3, and a palladium catalyst. The source of amine in this reaction was the polymer itself, which was an amide resin. 

In the case of unsymmetrical ketones, the attack usually comes from the less highly substituted side, so that CH3 is more reactive than RCH2, and the R2CH group rarely attacks. As in the case of 10-118, this reaction has been used to effect cycliza-tion, especially to prepare five- and six-membered rings. Nitriles are frequently used instead of ketones, the products being 3-keto nitriles. 

Keto nitriles, by cnnjugate addition of aldehydes, 59,5 6 KETONES, acetylemic, 55, 52... 

Keto nitriles, such as 138, function admirably as substrates in reductive cycliza-tions [56, 57], Two product types are obtained, one the simple ketone 140, the other 139, incorporating the a-hydroxy ketone (ketol) functionality that is present in many natural products (note Eq. 42). Both controlled potential and constant current conditions have been utilized. Of the electrodes examined (Ag, Cd, Pb, Zn, C-fiber, and Sn), tin generally proved most effective. Using tin, the controlled potential reduction of 138 in i-PrOH at —2.8 V vs SCE (divided cell, ceramic diaphragm) afforded a 76% yield of ketol 139 accompanied by 2% of ketone 140. As illustrated in Table 7, the preference for ketol formation drops when the transformation is carried out at constant current or without using a diaphragm. 

XLIV) centers about elaboration of hydroxymethylene ketone (574) into the tricyclic diketone (578). Alkylation of keto nitrile 575 proceeds exclusively cis to the angular methyl groups as does the subsequent reductive methylation. These authors were not able to achieve aldol cycUzation of keto aldehyde 576 and consequently proceeded to enol lactone 577 The addition of a methyl group to 578 could be achieved regioselectively. Subsequently dehydration gave 579 and its endocyclic isomer which were separated chromatographically. 

Acid derivatives that can be converted to amides include thiol acids RCOSH, thiol esters RCOSR,911 acyloxyboranes RCOB(OR )2,912 silicic esters (RCOO)4Si, 1,1,1-trihalo ketones RCOCX3,913 a-keto nitriles, acyl azides, and nonenolizable ketones (see the Haller-Bauer reaction 2-33). 

This method has been applied to a,(i-unsaturated ketones, esters, and nitriles to give the corresponding 1,4-diketones, y-keto esters, and y-keto nitriles, respectively (see also 6-54). 

Fluorinated esters may also act as electrophiles in reactions with nonfluori-nated ketones [28] (equation 23) or malononitrile [29] (equation 24). Unfortunately, the yields of p-diketones may be modest, but those of p-keto nitriles are excellent (Table 9)... 

Acylation of RMnI (10, 290).1 Acylating agents such as acyl halides and anhydrides react with RMnI to form ketones in high yield. This reaction can be used to provide acetoxy ketones, keto esters, keto nitriles, and diketones in generally high yield. 

The Knoevenagel reaction of aromatic and heteroaromatic aldehydes with cyanothioacetamides affords a-cyanothioacrylamides (126), which easily undergo thermal dimerization to 3,4-dihydro-2//-thio-pyrans (127). a-Keto-substituted acrylonitriles are synthesized by condensation of p-keto nitriles with aldehydes or ketones. - Benzoylacetonitrile self-condenses to afford (128), which can be transformed... 

When the nucleophile is an enolate, the addition reaction has a special name—it is called a Michael reaction. The enolates that work best in Michael reactions are those that are flanked by two electron-withdrawing groups enolates of j8-diketones, jS-diesters, 8-keto esters, and 8-keto nitriles. Because these enolates are relatively weak bases, addition occurs at the jS-carbon of a,)8-unsaturated aldehydes and ketones. The enolates also add to the S-carbon of a,)8-unsaturated esters and amides because of the low reactivity of the carbonyl group. Notice that Michael reactions form... 

---