2.4- Enynones 1,6-addition

Figure 3.45. Scope of Rh/(ff)-segphos-catalyzed asymmetric 1,6-addition of ArTi (Oi-Pr)4Li to conjugated enynones in the presence of Me3SiCl.

The synthesis of pent-4-en-l-yn-3-ones from alkynes involves their deprotonation and condensation with ot,(3-unsaturated aldehydes and subsequent oxidation of the allylic alcohol. A double thia-Michael addition occurs when the enynone is treated with sulfide which leads to 2,3-dihydrothiopyran-4-ones bearing different substituents at the 2- and 6-positions (Scheme 217) <2006TL5095>. 

Dihydrothiopyran-4-ones have been efficiently obtained from terminal alkynes through conjugate addition to a,/3-unsaturated aldehydes followed by oxidation to the enynone and cyclization <2007MC13>. The [2+2] photocycloaddition of ethylidenemalononitrile to the 2,2-dimethyldihydrothiopyranone is both regio- and stereo- specific <2007S1426>. 

Addition to an enynone (1). Cuprates, particularly higher-order ones, undergo 1,6-addition to 1 to provide the less stable (Z)-dienone 2 as the major product. The (Z)-stereoselectivity increases with the bulk of the transferred R group. The addition may involve an allenyl enol. Addition of QHjSLi to 1, however, provides (E)-dienones, possibly via an intermediate 1,2-adduct. 

Addition of organocuprates to cross-conjugated enynones leads to the dienones. Dimethyl sulfide stabilizes the cuprate adduct intermediates when it is employed as a reaction medium. ... 

B-Alkenyl- and B-l-alkynyl-9-borabicyclo[3,3,l]nonanes undergo smooth 1,4-addition to acyclic -unsaturated ketones. Cycloalk-2-enones do not yield any conjugate addition product. Furthermore the alkynylboranes react with acyclic /8-methoxy-a/8-unsaturated ketones to give conjugated enynones. ... 

The interesting dithia-analogue (317) of TXA has been prepared. This noteworthy synthesis commences with the readily available ketoester (313) and involves the conjugate addition of H S and Me02C(CH2)2S to the enynone (314) in the key steps. The monocyclic acetal (315) so formed was converted into the mesylate (316) which, on treatment with base and deprotection of the functional groups, gave the target molecule (317) (Scheme 44). 

A highly stereo- and regio-selective 1,4-addition of Grignard reagents to cyclic enynones with excellent ee values (up to 97%) for an all-carbon quaternary stereocentre has been developed. The use of Cu(OTf)2 and A-heterocyclic carbene ligand 0 (14) as the catalyst combination led to the unique formation of the 1,4-adduct. 

Scheme 49 Copper-NHC-catalysed ECA of Grignard reagents to cyclic enynones that bear additional unsaturations by Alexalds [84]...

The enynone product from the above reaction can further react with an organo-zinc or borane reagent in the presence of Ni(COD)2 and occasionally a phosphine ligand to produce diastereoselectively the corresponding bicyclononene derivatives in good yield. When EtjSiH is employed, a similar product with an addition of a hydridic moiety is observed [168]. 

Nucleophilic addition to enynones and 1,2-nucleophylic addition to y-ketoalkynes generate in situ the suitable functionalities for subsequent intramolecular hydroaUcoxylations under Pt(II) catalysis. 

Scheme 85 Pt02 catalyzed tandem nucleophiles addition/intramolecular hydroalkoxylation of enynones with nucleophiles...

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