This communication presents studies that nitroso Diels-Alder adduct has been furnished in uniformly high yield and high enantioselectivity using nitrosopyridine as a substrate and copper as a catalyst. The obtained Diels-Alder adduct was easily transformed to corresponding chiral amino alcohols without loss of enantioselectivity.

This communication presents studies that illustrated nitroso Diels-Alder adduct has been obtained in uniformly high enantioselectivity via a tandem nitroso aldol/Michael reaction using an amine catalyst. The regiochemical outcome of this construction is documented to be the opposite to that of the normal nitroso aldol reaction, which has been determined by X-ray analysis. The reaction of the enone with silver-BINAP catalyst has also been investigated in conjunction with the control of regiochemistry in a stepwise process.

During the past decade, the nitroso Diels–Alder (NDA) reaction has become more practical tool for organic synthesis, and a numbers of important compounds have been synthesized using this method. Until recently, no reports on a catalytic asymmetric version of this reaction had been reported; the major issues were the high reactivity of nitroso compounds and their chemical properties. This microreview outlines recent advances in the area of asymmetric NDA reaction following the review by Streith and Defoin in 1994. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

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).

This article presents complete diastereo- and highly enantioselective synthesis of nitroso Diels-Alder-type bicycloketones using dienamine. With the hydrogen bonding of two hydroxyls in the bulky binaphthol 1c, high enantioselectivities and complete diastereoselectivity are realized in 2-oxa-3-aza-bicycloketone synthesis. On the other hand, alpha,beta-unsaturated ketone can be employed as diene precursor, utilizing readily available tetrazole catalyst 3b, to provide the 3-oxa-2-aza-bicycloketones in moderate yields with complete enantioselectivities. Investigation into the reaction utilizing 2-morpholino-4,4-diphenylcyclohexadiene 2d clearly indicated that cyclization with the bulky binaphthol 1c is involved in the sequential process, the N-nitroso aldol reaction, followed by Michael addition. In addition, optically pure 1-amino-3,4-diol is synthesized from 2-oxa-3-aza-bicycloketones. Use of p-phenoxynitrosobenzene allows access to protected amino diol via cleavage of the N-Ph bond.