~ ~~~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.

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The Diels-Alder reaction of cis-5,6-diacetoxy-l,3-cyclohexadiene (l), which has a rneso configuration, with the chiral nitroso dienophile 2 occurs with induction of four asymmetric centers in very high optical yield (ee = 94%) and leads to the dihydro oxazine 3 (89%). The influence of the reaction temperature on the asymmetric induction was investigated and the absolute configuration of the product determined. Reductive cleavage of the N -0 bond of 3 presents a simple route to enantiomerically pure derivatives of (1R)-conduramine A1 (82%).Aminocyclitols are essential structure elements of many biologically active compounds. They have been found in aminoglycoside-aminocyclitol (AGAC) antibiotics'), in Amaryllidaceae alkaloids ' ' , and as ligands of cytostatic platinum complexes3'. In connection with our work on the mutasynthesis of new AGAC4' we are interested in the enantioand stereoselective synthesis of aminocyclitols. The key step in our synthetic pathway is the hetero Diels-Alder reaction of activated nitroso compounds with substituted cyclohexadienes ' I. Diacetoxydiene 1 was obtained by acetylation of cis-5,6-dihydroxy-l,3-cyclohexadiene with acetic anhydride and pyridine in nearly quantitative yield. This dihydroxy diene was prepared by Nakajima from tetrachlorodihydroxycyclohexane6); it is also available by microbial dioxygenase oxidation of benzene'). A biotechnological process using mutants of Pseudomonas putida was recently developed and allows the synthesis of the dihydroxydiene in multikilogram amounts *). HN: HCI)(' ova NO CHCLJEtOH &OAc a :The Diels-Alder reaction of 1 with the protected l-chloro-1-nitrosomannose') 2 yields the dihydro oxazine 3. The stereochemistry of 3 was determined from the 'H-NMR spectrum. The chemical shifts of the acetyl proton signals at 6 = 2.01 and 2.03 prove the endo position of the acetoxy groups. Signals of acetyl groups in exo positions, which are not shielded by the anisotropic effect of the double bond, would be expected at 6 = 2.15"). The chemical shifts of the 7-H (6 = 5.38) and 8-H (6 = 5.50) signals are characteristic for exo protons and confirm this assignment.For the investigation of the stereo-and enantioselectivity, we carried out a number of Diels-Alder reactions at different temperatures and isolated product 3 without recrystallization. After disappearance of the blue color of the nitroso compound, the reaction mixtures were extracted with water, and the product mixtures were lyophilized. The 'H-NMR spectra of the crude products showed that the reaction is stereoselective even at room temperature. The attack of the dienophile 2 obviously takes place only anti to the acetoxy substituents, from the sterically less shielded face of diene 1. The enantioselectivities of the Diels-Alder reactions were determined by establishing the enantiomeric purity of the dihydro oxazines using derivatization of the crude products with (S)-3,3,3-trifluoro-2-methoxy-2-phenylpropionyl chloride, separation of the diastereomeric amides by HPLC, and integration of the individual ...

Diastereoselective Diels-Alder Reactions with a-Chloronitroso SaccharidesThe a-chloronitroso reagent 2 obtained from ribose via the lactone oxime 3 reacts with the dienes 6 -10 at low temperature to give the chiral dihydrooxazines 11 -16 in 63 -96% yield and >96% enantiomeric excess. The reagents 1 and 2 which are approximately mirror images in the vicinity of the chloronitroso function lead to opposite enantiomers of 11 -16. The absolute configuration of the products was determined by chemical degradation and comparison with authentic amino and hydroxy acids.Im Rahmen unserer Arbeiten uber Synthesen von optisch aktiven Aminocyclitolen wenden wir diastereoselektiv verlaufende [4 + 21-Cycloadditionen wobei als Heterodienophile enantiomerenreine a-Chlornitrosoverbindun-Schema genr4' eingesetzt werden. Als besonders giinstiges Reagenz, sowohl was Zuganglichkeit, Lagerbarkeit und Reaktivitat betrifft, als auch bezuglich der erzielbaren chemischen und optischen Ausbeuten, hat sich die aus Mannose zugangliche gezeigtL7"], daD die [4 + 21-Cycloadditionen von 1 mit den 1,3-Dienen 6-9 in guten Ausbeuten und rnit ee-Werten 2 9 6 % die Dihydrooxazine 11-14 ergeben (vgl. Tab. 1). Die absoluten Kodigurationen der aus 1 erhaltenen DielsAlder-Adukte waren, mit einer Ausnahme, nicht bekannt.Wir berichten hier iiber die Synthese der aus Ribose zuganglichen a-Chlornitrosoverbindung 2, ihre Diels-AlderSchema 1Reaktionen mit den Dienen 6-10 und uber die absolute Konfiguration der aus 1 oder 2 erhaltenen Produkte.

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