Oxo-Michael addition

Roush WR, Hall SE (1981) Studies on the total synthesis of chlorothricol-ide stereochemical aspects of the intramolecular Diels-Alder reactions of methyl undeca-2,8,10-trienoates. J Am Chem Soc 103 5200-5211 Rudler H, Denise B, Xu Y, Parlier A, Vaissermann J (2005) Bis(trimethylsilyl)-ketene acetals as C,0-dinucleophiles one-pot formation of polycyclic y-and 8-lactones from pyridines and pyrazines. Eur J Org Chem 3724-2744 Sekino E, Kumamoto T, Tanaka T, Ikeda T, Ishikawa T (2004) Concise synthesis of anti-HIV-1 Active (+)-inophyllum B and (+)-calanolide A by application of (-)-quinine-catalyzed intramolecular oxo-michael addition. J Org Chem 69 2760-2767... 

Using ( )-Quinine Catalyzed Intramolecular oxo-Michael Addition ... 

Ishikawa et al. reported that ( )-quinine-catalyzed asymmetric intramolecular oxo-Michael addition (IMA) of 7-hydroxy-8-tigloylcoumarin gave cis-2,3-dimethyl-4-chromanone systems with high enantioselectivity and moderate diaster-eoselectivity, especially when chlorobenzene was used as a solvent. " Therefore, total synthesis of (+)-calanolide A (1) was achieved by application of the (—)-quinine-catalyzed asymmetric IMA. However, the synthetic route starting from 1,3,5- trimethoxybenzene was too long (13 steps with 3.5% overall yield) to practice. Finally, the authors improved and shortened the original synthetic route by application of Mgl2-assisted demethylation. 

Sekino, E. Kumamoto, T. Tanaka, T. Ikeda, T. Ishikawa, T. Concise synthesis of anti-HIV-1 active (-l-)-inophyllum B and (-l-)-calanolide A by application of (—)-quinine-catalyzed intramolecular oxo-Michael addition. J. Org. Chem., 2004, 69 2760-2769. 

Tanaka, T. Kumanoto, T. Ishikawa, T. Solvent effects on stereoselectivity in 2,3-dimethyM- chromanone cyclization by quinine-catalyzed asymmetric intromolecular oxo-Michael addition. Tetrahedron-Asymmetry, 2000, 11 4633 637. 

Quite recently, the use of natural cinchona alkaloids as catalysts for the intramolecular oxo-Michael addition of o-tigloylphenol (3), furnishing chiral ris-2,3-dimethyl-4-chromanone 4, which is a valuable intermediate for the synthesis of the anti-HIV-1 active coumarins, (+ )-calanolide A (5a), and (+ )-inophyllum B (5b), was reexamined by Ishikawa and coworkers (Scheme 9.2) [2], The parent cinchona alkaloids,... 

A broad range of enantiomericaUy pure 4,5-dihydrobenzo[r [l,3]diox-epines 177 have been prepared via a four-component Mannich reaction and subsequent intramolecular oxo-Michael reaction (14CC2196). The reactions proceeded with both high enantio- and diasteroselectivity, utilizing a dual catalytic system of Rh2(OAc)4 and a chiral phosphoric acid 178. The rhodium catalyst forms the protic oxonium ylide 174 from a diazo compound 171 and this subsequently adds to imine 175, formed in situ. The resulting enantiomericaUy enriched intermediate 176 then undergoes an intramolecular and diastereoselective oxo-Michael addition to form the final product 177. 

Scheme 15.25 S cnthesis of some anti-HIV-1 active drugs by quinine-catalysed intramolecular oxo-Michael addition.

Scheme 114 Quinine-catalyzed oxo-Michael addition in the total syntheses of (-i-)-calanolide A (535) and (-l-)-inophyllum B (536)...

Sekino E, Kumamoto T, Tanaka T, Ikeda T, Ishikawa T (2004) Concise Synthesis of Anti-HIV-1 Active (+)-Inophyllum B and (-t)-Calanolide A by Application of (-)-Quinine-Catalyzed Intramolecular Oxo-Michael Addition. J Org Chem 69 2760... 

Under presented conditions (triazolium bromide XI and DBU in CHjCy, the reaction proceeds by a cascade reaction (i) first, amidation (aza-benzoin condensation between enal and nitrosoarene, as outlined in Scheme 5.33) produces A-hydroxyacrylamide 51, and (ii) second, in the presence of base such as DBU or triazole carbene [41], oxo-Michael addition of 51 to enones would afford products 52 (Scheme 5.35). 

SCHEME 5.35 Base promoted oxo-Michael addition of 51 to enones. 

Aroylvinylarylaldehydes (108, Ar = furyl, thiophenyl or pyridyl) react with nitrosoarenes to give heterocyclic ring-fused 1,2-oxazinones (109), using NHC catalysis. Intermediate formation of A-hydroxylamides followed by intramolecular oxo-Michael addition is discussed. 

Alkaloid 1 also catalyzed the asymmetric intramolecular oxo-Michael addition of o-tigloylphenol in chlorobenzene, leading to ctx-2,3-dimethyl-4-chromanone (Scheme 6.3) [18], a valuable intermediate in the total synthesis of (+)-calanoUde A and (+)-inophyllum B. 

The first organocatalytic oxo-Michael addition to enals was reported by Jot-gensen in 2007 [65], Jorgensen used as a suitable nucleophile benzaldehyde oxime, which reacts with enals with catalysis by 28. The resulting product, reduced directly to the alcohol due its UabiUty, was obtained in excellent yields and enan-tioselectivities (Scheme 33.20). The oxime moiety can easily be cleaved to afford the 1,3-diols without loss of enantiomeric purity. However, aromatic enals turned out to be unreactive in this transformation. 

---