Enones Grignard additions

When the 4-position is substituted, Grignard addition occurs at the 2-position, to eventually give a 2,4,6-trisubstituted pyridine via the 6-lithiated species (Scheme 145) (88TL1751). Alternatively, if the 4-substituent is a chloro (88TL1751) or methoxy group (89TL5053), the initial product can be hydrolyzed to an enone rather than being aromatized to a pyridine. 

The as-decalin is formed because the enone, though flattened, is already folded to some extent. A conformational drawing of either molecule shows that the top surface is better able to bind to the flat surface of the. catalyst. Each of these products shows interesting stereoselective reactions. The ketal can be converted into an alkene by Grignard addition and El elimination and then epoxidized. Everything happens from the outside as expected with the result that the methyl group is forced inside at the epoxidation stage. 

Note that in the above procedure the enone is added to an excess of the Grignard reagent. If conditions are employed which permit the simultaneous presence of the enolate resulting from 1,4-addition and the enone. Michael addition of the former to the latter leads to 1,3,5-triphenyl-2-(diphenylmethyl)pentane-l, 5-dione (5). 

Grignard Addition to Enones. The sultam generated from camphorsulfonic acid can also be used as a chiral auxiliary in the conjugate addition of Grignard reagents to enones. Simple alkylmagnesium chlorides add in a 1,4-fashion to afford imides (eq 19). ... 

The damascones are a group of materials related to the ionones, but in which the enone unit is transposed. They are components of rose oils and have very intense fruity-floral odours. The damascenones, which contain a second double bond in the ring, are also very much sought after. One synthesis of a-damascone from methyl a-cyclogeranate is shown in Scheme 4.40. A double Grignard addition gives the tertiary alcohol. Heating of this in the presence of base, to prevent elimination... 

The disconnection for these three-component syntheses is to remove the trans substituents from the a and P positions. Thus the ketone 65 disconnects to the enone 66, a vinyl-Cu derivative and an electrophilic bromoester. In the event, a Cu2I2 catalysed Grignard addition followed by alkylation of the magnesium enolate gives pure trans-65 in 91% yield.27... 

Conjugate addition of vinyllithium or a vinyl Grignard reagent to enones and subsequent oxidation afford the 1.4-diketone 16[25]. 4-Oxopentanals are synthesized from allylic alcohols by [3,3]sigmatropic rearrangement of their vinyl ethers and subsequent oxidation of the terminal double bond. Dihydrojasmone (18) was synthesized from allyl 2-octenyl ether (17) based on Claisen rearrangement and oxidation[25] (page 26). 

Use of the imonium group for protection of enones was explored. Stability to peracids, lead tetraacetate, bromine, and acetic anhydride was claimed (727). The usual resistance of enamines (but not their salts) to additions of Grignard reagents was used for selective addition to a 3,17-diketosteroid by formation of the usual 3-monoenamine 728). 

The reversal of the stereoselectivity is attributed to the ability of chlorotrimethylsilane to trap the initially formed cuprate-enone complex, thereby suppressing equilibration of the diastereomeric complexes. The copper-catalyzed 1,4-addition of Grignard reagents to 5-substituted 2-cyclo-hexenone also proceeded with very high trans diastereoselectivity22. 

Example Sometimes copper solves other regioselecL-ivity problems. Addition of aryl Grignard (28) to enone (29) gives the anomalous product (30) in which the electrophile (29) has been attacked at the right atom but the nucleophile (23, arrows) has attacked with the wrong atom. 

Example The lactone (8>, needed for a natural product synthesis, might be made from (6) via epoxide (7) and so a synthesis for (6) was required. Wittlg disconnection reveals a 1,5-dicarbonyl compound (9), best made by Michael addition of a substituted malonate (11) to enone (10). The enone was made by the simple but reliable Grignard route rather than risking a Mannich reaction of unknown regloselectivity. 

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