Catalytic enantioselective Michael addition

Methods for the catalytic enantioselective Michael addition have been developed using three different approaches ... 

Table 7.6 Catalytic enantioselective Michael addition using L-tartrate-derived PTCs.

In another study Feringa et al. [20] reported a catalytic enantioselective three-component tandem conjugate addition-aldol reaction of dialkyl zincs. Here, zinc enolates were generated in situ via catalytic enantioselective Michael addition of dialkylzinc compounds to cydohexenone in the presence of a chiral Cu catalyst. Their diastereoselective reaction with an aldehyde then gave trans-2,3-disubstituted cyclohexanones in up to 92% yields and up to >99% ees (Scheme 9.11). 

Table 4.6 Catalytic enantioselective Michael addition of 28 to a,/ -unsaturated carbonyl compounds under phase-transfer conditions. (For experimental details see Chapter 14.9.11).

N. Krause, A. Hoffmann-Roder, Recent Advances in Catalytic Enantioselective Michael Additions, Synthesis 2001, 171-196. 

Krause, N., Hoffmann-Roder, A. Recent advances in catalytic enantioselective Michael additions. Synt/res/s 2001,171-196. 

A catalytic enantioselective Michael addition of diisopropyl malonate to a,p-unsaturated ketones and aldehydes has been achieved using 5 mol% of the... 

Chen developed a catalytic enantioselective Michael addition of trimethylsilylcyanide to chalcones by using chiral 3,3 -(l-adamanthyl)2-BINOL-derived sodium phosphate, which was prepared in situ from 57 and NaOH, in the presence of 2-fert-butylphenol (Scheme 2.36). The reactions proceeded at 78 °C within 3 h, and the corresponding p-cyano ketones were obtained in high yields with moderate enantioselectivities (up to 72% ee). 

Scheme 10 Catalytic enantioselective Michael addition-allylic alkylation cascade...

In 2006, catalytic enantioselective Michael addition of ketene silyl acetals to cyclic and acyclic a, P-enones was devised using the chiral BLA (3a) (Scheme 1.6) [8]. Various Michael donors and ketene silyl acetals can be employed for this process. Here again, the use of triphenylphosphine oxide is crucial to trap any catalytically active silyl cation species. In addition, the combined use of triphenylphosphine oxide and a stoichiometric amount of 2,6-diisopropylphenol (which acts as a scavenger of silyl cation species) is sometimes required to get both high enantioselectivity and the chemical yield. This enantioselective methodology was applied to the asymmetric synthesis of a key intermediate of caryophyllene. 

Enantioselective Michael addition catalyzed by chiral aluminum Lewis acid is one of the most important methods to obtain enantiomerically pure compounds. As an early work in this fleld, in 1986, Shibasaki and coworkers reported catalytic enantioselective Michael addition of malonates to cyclic enones catalyzed by Li-Al bimetallic catalyst (72) (ALB) derived by premixing LiAlH4 and 2 equivalent of (R)-BINOL in THF (Scheme 6.86) [106, 107]. The structure of (R)-ALB was confirmed by X-ray crystallographic analysis of ALB-cyclohexenone complex. One notable advantage of ALB catalyst is that it works nicely in the tandem Michael-aldol sequence. 

Enantioselective Michael addition of malonates to a,p-unsaturated carbonyls with Al(salen) complex was firstly reported by Jha and Joshi in 2001. They reported the formation of Al-Na bimetallic Al(salen) complex (73b) from (R,R)-salen and NaAlH2(OCH2CH20Me), and catalytic activity for catalytic enantioselective Michael addition of malonic diesters to cyclic a,P-enones (Scheme 6.93) [111]. In the reaction of cyclopentenone with various malonates, this catalyst resulted in good chemical yield and moderate enantioselectivity. 

Bandini and Umani-Ronchi reported catalytic enantioselective Michael addition of indoles to a,P-unsaturated ketones (Scheme 6.95) [113]. In this reaction, the combined use of Al[(R,R)-salen]Cl complex (67a) and 2,6-lutidine is necessary to obtain Michael adducts in high enantiomeric excess. Among various amines, 2,6-lutidine... 

CATALYTIC ENANTIOSELECTIVE MICHAEL ADDITION OF 1,3-DICARBONYL COMPOUNDS TO CYCLIC ENONE FOR THE SYNTHESIS OF THE STRYCHNOS ALKALOIDS AND MAGNOLIONE ANALOGS... 

The highly enantioselective calcium phosphate (392) catalysed chlorination of 3-substituted oxindoles (387) with A -chlorosuccinimide (NCS, 388) in the catalytic enantioselective Michael addition of (387) to methyl vinyl ketone (389) to afford the product (390) and (391) in quantitative yields, with high enantioselectivities, has been described by Antilla et al. (Scheme 102). ... 

---