Diastereoselectivity and Reactivity in the Diels‐Alder Reactions of α‐Chloronitroso Ethers

Abstract

~ ~~~The structure of the a-chloronitroso ether I, obtained from the hydroximolactone 2 and tert-butyl hypochlorite (89 %), was established by X-ray crystallographic analysis. The [4 + 2 1 cycloadditions of 1 with the dienes 3 and %I1 led to the N-unsubstituted 3,6-dihydro-2H-1,2-oxazines 6 and 12-16 in high enantiomeric excess ( Table 1). Due to the additional a-alkoxy group, the reactivity of 2 is much superior to the one of known a-chloronitrosoalkanes. The reactive conformation of 1 was deduced from the X-ray analysis as well as the high diastereoselectivity of the cycloadditions. The importance of the a-alkoxy group was evidenced from the similar reactivity of the racemic a-chloronitroso ethers 2 5 2 7 which were prepared from the hydroximo ethers 28-30 and tert-butyl hypochlorite.

Asymmetric synthesis of pentono‐ and 6‐deoxyhexono‐δ‐lactams via hetero‐Diels‐Alder reactions with nitroso dienophile

“…Kresze and coworkers had proven the (3 R,6R)-configuration for the adduct of ethyl sorbate with dienophile 3 [24] [33]; the same configuration was deduced for adduct 4b and 5b by analogy. The (6R)-configuration for the monosubstituted adduct 4a and 5a was corroborated by comparison of the physical data of the final pentono-&lactams with those of the literature [26-291. The optical purity of the adducts 4a, b was determined by HPLC on chiral columns (Chiralpack A D or Chiralcel O D ) with their protected derivatives 5a, b, racemic (-k)-5a, b being used as references.…”

“…For completion of the reaction, it was best to add the catalyst twice [23]. Physical data of the known h-lactams were in good agreement with literature data for D-ribonolactam 13a [26- The regiospecificity of the hetero-Diels-Alder addition was assumed to be the same ;IS for other sorbic-acid derivatives as determined by Krcszr et al [24] [33] or by us 1321 [23] [34], i.e., the 0-atom of the nitroso compound is bound to the a-position of the carboxylic group. Direct determination was possible by 'H,13C-NMR correlation.…”

“…In the pyrrolidinone series, amidrazones, which are obtained from D-ribono-y-lactam, are potent nucleotide hydrolase inhibitors We describe herein a straightforward synthesis of 5-amino-5-deoxypentono-and 5-amino-5,6-dideoxyhexono-6-lactams 13a, 14, 15a, 16, 13b, and 15b in the D-ribose, L-arabinose, D-xylose, L-lyxose, D-allose, and D-glucose series, respectively, starting from the readily available (E)-pentadienoic acid 2a [21] and from the commercial (E,E)-hexadienoic acid (= sorbic acid) 2b. The synthetic methodology has already been presented by us for the preparation of 6-deoxy-amino-sugars and of their I-deoxy derivatives from hexadienal dimethyl acetal or 0-methyloxime [22] [23] and consisted of an asymmetric hetero-Diels-Alder reaction with the chiral chloro-nitroso derivative 3 of D-mannose [24], followed by cis-or truns-dihydroxylation and cleavage of the oxazine ring by hydrogenolysis. This reaction scheme starting from methyl sorbate has been described in the racemic series by Belleau and AM-Young in 1963 to give linear 5-amino-5,6-dideoxyhexonic acids in the allonic and allegedly gulonic, in fact gluconic series 5-Amino-5-deoxypentono-6-lactams in the D-ribose [26-281, D-xylose [27] [29], Dlyxose [27], D-and DL-arabinose [27][30] series were already known compounds.…”

“…was prepared according to [34][49] (OsO, (I g) and 70% t-BuOOH To a stirred soln. of 3 [24] (10 g, 32.5 mmol) in CH,CI, (74 ml) under Ar at -10 ', 2a (3.5 g, 35.7 mmol, 1 .I equiv.) in dry EtOH (19 ml) was added.…”

“…Asymmetric Diels-Alder Reaction and Optical Purity (Scheme I ) . -Asymmetric DielsAlder reaction of chloro-nitroso compound 3 with the dienoic acids 2a, b was carried out according to Kresze's conditions, i. e., in CH,CI,/EtOH solutions at -10" overnight [24]; the adducts 4a, b crystallized as hydrochlorides in ca. 75 YO yield after addition of dry Et,O.…”