Catalytic Asymmetric Nitroso‐Diels–Alder Reaction with Acyclic Dienes

Abstract

Keywords amino alcohols; asymmetric catalysis; cycloaddition; dienes; nitroso compoundsThe nitroso-Diels-Alder reaction has long been a valuable synthetic operation for multistep syntheses given that the resulting adducts serve as 1-amino-4-hydroxy-2-ene derivatives after a single step. Subsequent to earlier studies by Kresze and co-workers[1] on the use of simple nitroso derivatives, many research groups have made significant contributions to the steady improvement of this methodology.[2] Recently, we enhanced this transformation to catalytic and enantioselective methods through the use of nitrosopyridine as a dienophile in the presence of a chiral copper catalyst.[3] Unfortunately, the new asymmetric reaction did not proceed as smoothly for acyclic dienes as it did for cyclic systems, which therefore limits its range of application. Herein, we report catalytic regio-, diastereo-, and enantioselective nitroso-Diels -Alder reactions of acyclic 2-silyloxy-1,3-dienes that have a broad substrate scope. The pathway for the present catalytic enantioselective transformation is outlined in Scheme 1.The nitroso-Diels-Alder reaction of pentadiene and 6-methyl-2-nitrosopyridine in the presence of [Cu(MeCN) 4 -(segphos)]PF 6 gave a mixture of 1-and 4-amino derivatives in a 3:1 ratio with up to 10% ee. The reactivity of the diene was increased, and (2Z,4E)-3-trimethylsilyloxy-2,4-hexadiene[4] (1a) was examined in the presence of a catalytic amount of [Cu(MeCN) 4 (segphos)]PF 6 . Although this experiment gave complete regioselectivity[5] (4-silyloxy/5-silyloxy ≥ 99:1), the enantioselectivity (16% ee for the 4-silyloxy derivative) remained low. Surprisingly, the low enantioselectivity was improved significantly by simply increasing the size of the silyl group (1aγ1bγ1c): Up to 98% ee in the presence of Cu I -segphos [6] and > 99% ee with [Cu(MeCN) 4 -(difluorophos)]PF 6 [7] were attained in the reaction of the triisopropylsilyl derivative 1c (Table 1).

Asymmetric Hetero Diels-Alder Reaction of Nitroso Compounds Utilizing Tartaric Acid Ester as a Chiral Auxiliary

“…The resulting mixture was kept for 24 h at 0 °C and then treated with a saturated aq NH 4 Cl solution. After warming to rt, the solvent was removed in vacuo and the residue was partitioned between EtOAc and water.…”

“…The resulting mixture was kept for 20 h at 0 °C and then treated with a saturated aq NH 4 Cl solution, and the solvent was evaporated. The organic substances were extracted with EtOAc, followed by washing with H 2 O, brine, and dried over Na 2 SO 4 .…”

“…2.3 Very recently catalytic hetero Diels-Alder reactions of nitroso compounds catalyzed by chiral metal complexes were reported. [4][5][6][7][8] our laboratory and it has been successfully applied to the asymmetric 1,3-dipolar cycloaddition reaction. 9 The promising results obtained from the 1,3-dipolar cycloaddition tempted us to apply this strategy for the enantioselective hetero Diels-Alder reaction of nitroso compound by the use of tartaric acid ester as a chiral auxiliary.…”

5.10 Hetero-Diels–Alder Reactions

“…103 In this reaction, the use of (S)-DIFLUORPHOS (200) as the ligand gives better results than (S)-SEGPHOS (197). The OTIPS dienes 201 show higher reactivity and enantioselectivity than the corresponding trimethylsilyloxy (OTMS) or tert-butyldimethylsilyloxy (OTBDMS) dienes.…”

Recent progress in a chiral multinucleating system utilizing tartaric acid esters

“…Recently catalytic hetero Diels-Alder reactions of nitroso compounds catalyzed by chiral metal complexes were reported. 21 When dienol 14 is successively treated with diisopropylzinc, (R,R)-DIPT, and propylzinc bromide, a zinc-bridging intermediate shown in 16 would be presumably formed. To the intermediate is added a nitroso compound 15, it can be activated and well oriented to allow the subsequent hetero Diels-Alder reaction in an enantioselective manner and the corresponding optically active dihydro-1,2-oxazine derivatives 17 is expected to be produced (Eq.…”