Phosphites with enones

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. 

A remarkable number of chiral phosphorus ligands (phosphoramidites, phosphites, and phosphines with modular structures) have been introduced into the copper-catalyzed conjugate addition of R2Zn reagents, and high enantio-selectivities (>90%) are now possible for all three different classes of substrates 2-cyclohexenones and larger ring enones, 2-cyclopentenones, and acyclic enones. 

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. 

The use of copper catalysts based on chiral phosphorus ligands to assist 1,4-additions of dialkylzinc reagents has in recent years produced major breakthroughs, with excellent enantioselectivities. A number of monodentate and bidentate phos-phoramidites, phosphites, phosphonites, and phosphines are now available as chiral ligands for alkyl transfer to a variety of cyclic and acyclic enones. So far. 

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). 

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). 

Diastereoselective complexations affording chiral heterodiene complexes are also known (Scheme 74) 374-376 complexation of the enantiomerically pure iV-benzyl vinylim-ines was shown to proceed under kinetic control equilibration to thermodynamic mixtures possessing poorer diastereomer ratios occurred upon standing. On the other hand, the diastereoselective complexation of an enantiomerically pure enone with a side chain possessing chirality and a chelating phosphite group was shown to proceed under thermodynamic control (Scheme 75). The product (a single diastereomer was formed) could be transformed by nucleophihc addition at the -position. 

Alejcakis et al. synthesized a large variety of TADDOL-based phosphites phos-phoramiditeSj and phosphonites 28 and screened these ligands in the Et Zn addition to 2-cydohes enone (Scheme 7.13) [53 54]. While only modest ees were reported for most of these ligands an excellent yield (95%) and enantioselectivity (96%) was observed with ligand 29. The stereocontrol in these ligands is mainly due to the TADDOL moiety. 

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. ... 

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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