Enones, reactions with phosphites

Reaction with aji-unsaturated ketones and lactonesThe reactivity of a,/ -enones to singlet oxygen depends on the conformation. Systems that exist in s-trans-conformations (e.g., A4-3-ketosteroids) react slowly if at all. However, s-cis-enones react readily. For example, (R)-( + )-pulegone (1) reacts to give the products 2-4. The same products are obtained by oxidation with triphenyl phosphite ozonide (3, 324 325). 

Conjugate additions. p-Silyl ketones are formed from enones by their reaction with disilanes in the presence of Cu(OTf)j and BUjP. The ethyl transfer from EtjZn is accelerated by catalytic amounts of Cu(OTf)2 and/or triethyl phosphite. ... 

Aside from the titanium-mediated process described above, the asymmetric addition of aUcyl groups to aldehydes can also be performed by nickel catalysts. This traces back to seminal work of Fujisawa et al. who had found that the addition of AlMc3 to aldehydes can be catalyzed by Ni(acac)2 and is strongly accelerated by phosphines and phosphites [50]. Racemic additions to aromatic and aliphatic aldehydes thus occurred in good yields with as little as 0.1 mol% of nickel. Interestingly, the reaction with AlEt3 and Al(/Bu)3 predominantly led to the respective addition products with only small amounts of the reduced primary alcohols. This is in contrast to the nickel-catalyzed 1,4-addition of higher aluminum trialkyls to enones, in which the rate of p-hydride elimination surpasses that of 1,4-addition [51]. 

Phosphite compounds, which have been discussed in the context of their application in asymmetric hydrogenation reactions (see Section 6.1.2.6), can also be used to effect the copper salt-mediated asymmetric conjugate addition of diethylzinc to enones.74 As shown in Scheme 8-33, in the presence of diphosphite 92 and copper salt [Cu(OTf)2], the asymmetric conjugate addition proceeds smoothly, giving the corresponding addition product with high conversion and ee. In contrast, the monophosphite 93 gave substantially lower ee. 

Alexakis et al,231 reported copper-catalyzed enantioselective Michael additions in the presence of various 2-arylcyclohexyl-substituted phosphites. Ligand 279 turned out to be particularly efficient for the 1,4-addition of organozinc reagents to cyclopentadec-2-enone. Whereas Et2Zn gave the addition product with 87% ee, the corresponding reaction of dimethylzinc furnished (R)-(—)-muscone with an enantiomeric excess of 79% ee (Scheme 74). 

Ohler, E., and Zbiral, Ii., Reaction of dialkyl phosphites with a-enones. Part 1. Synthesis and allylic reanangement of dimethyl (l-hydroxy-2-alkenyl)- and (l-hydroxy-2-cycloalkenyl)phosphonates, Chem. Ber.. 124, 175, 1991. 

Usually no reaction of alkenyloxiranes bearing a methyl group at the terminus as in 149 takes place instead isomerization to enone occurs. The reaction of the epoxide 149 with the Meldrum s acid derivative 148 proceeded at room temperature in THF using a precatalyst generated by mixing Pd2(dba)3 (1.5 mol%) and cyclic phosphite TMPP (III-2) (20 mol%) to afford 150 in 75 % yield, and macrolactam aglycon of fluviricin B1 was synthesized [53]. 

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