The First Enantioselective Aza-Diels-Alder Reactions of Imino Dienophiles on Use of a Chiral Zirconium Catalyst

Abstract

Chiral dihydropyridone derivatives 3 are obtained in high yields and with good enantioselectivities by the title reaction of aldimines such as 1 with Danishefsky's diene 2. 6,6'-Dibromo-1,1'-binaphthol complexes with Group 4 metals serve as catalysts; zirconium proved to be especially effective.

Diastereoselective Cycloadditions of Chiral Non-racemic Azomethine Imines

“…(c) Cyclic carbazate structure should lead to an almost planar ylid, with the phenyl ring pushed out of this plane by A (1,3) strain, allowing good facial selectivity.…”

“…

3,4]oxadiazinan-2-one (6) is an easily available building block and acts as a chiral non-racemic precursor for azomethine imines. The ylid can be formed regioselectively with various aldehydes and reacts in an efficient manner with a wide range of dipolarophiles.

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“…Phenyl[1,3,4]oxadiazinan-2-one (6) Compound 5 (11.52 g, 43.0 mmol) was stirred 48 h in anhyd MeOH (300 mL) under 10 bars hydrogen atmosphere in presence of a small amount of 20% palladium hydroxide on carbon. The mixture was then filtered, concentrated and recrystallized from THF to give 7.42 g of compound 6 as white crystals(97 %); [a] D 20 -10.5 (MeOH, c = 0.85); mp = 170-172 °C.…”

Asymmetric aza-Diels-Alder reaction of Danishefsky's diene with imines in a chiral reaction medium

“…So far, a few catalyst systems have been quoted in relation to the asymmetric process. Among them are: the zirconium-binaphthol complexes developed by Kobayashi et al ., [ 8 - 11 ] the silver catalysts of phosphine peptide Schiff bases reported by Snapper and Hoveyda,[ 12 ] as well as the copper complexes of BINAP and phosphino-oxazolidines described by Jørgensen,[ 13 , 14 ] and the chiral copper complexes of phosphino sulfenyl ferrocenes reported by Carretero. [ 15 ] The catalyst systems also include the Lewis acid catalysts based on boron-BINOL complexes [ 16 - 18 ] and lastly zinc-BINOL complexes developed by Whiting et al .…”

5.10 Hetero-Diels–Alder Reactions

“…The chiral zirconium(IV) complex 118 ( Figure 9) prepared from Zr(OBu t ) 4 , (R)-6,6 0 -dibromo-1,1 0 -binaphthol, and N-methylimidazole catalyzes the aza-Diels-Alder reaction of aldimine 122 with Danishefsky-type diene 121 to give cycloadducts 123 in high yields with high enantioselectivities (equation 13, Table 19). 71 The use of N-methylimidazole as an additional ligand gives the best results. Although various aromatic aldimines are converted to the corresponding adducts with high enantioselectivities, the reaction of cyclohexyl (Cy)-substituted aldimine (R 2 ¼ c C 6 H 11 , R 3 ¼ H) shows low enantioselectivity.…”