On the mechanism of diels‐alder reactions of nitroso alkenes: exo/endo selectivity, stereospecificity, E/Z selectivity, and relative reactivity of various olefins

Abstract

The mechanism of the hetero Diels-Alder reaction of nitroso alkenes 2 with silyl enol ethers and other olefins has been investigated. Using the bicyclic nitroso compound 2a a study of the exolendo selectivity has demonstrated that the ex0 approach is preferred with the siloxyethene l a as dienophile. On the other hand, the siloxycyclopentene 1 c gives a mixture of cycloadducts 3c with an excess of endo product (endo: exo 82: 18). The stereospecificity of the nitroso alkene cycloaddition could be demonstrated with the stereochemically homogeneous silyl enol ethers 1 b and 1 d. Experiments with enol ethers 1 f and 1 g also occur stereospecifically. a-Nitrososty-rene 2b reveals surprisingly high kEIz values when EIZ-isomeric olefins are compared in competition experiments. Also, a detailed reactivity scale of 2b including various structurally different silyl enol ethers and other typical dienophiles shows that a complex interplay of electronic and steric effects is operating. The large influence of steric effects is taken as evidence for a highly ordered transition state in the cycloaddition. All mechanistic details for the Diels-Alder reactions of nitroso alkenes 2 with (silyl) enol ethers are in strong accord with a concerted mechanism and exclude the involvement of zwitterions or diradicals as intermediates.In a previous account3' we have reported on the regioselective synthesis of 6-siloxy-substituted 5,6-dihydro-4H-1,2-0xazines (abbreviated as 1,2-oxazines) from silyl enol ethers 1 and nitroso alkenes 2. According to Gilchrist4), reactive intermediates 2 are easily generated in situ by base treatment of the corresponding a-halogen oximes. R G R RSSiO 2Characteristic features of this cycloaddition are high yields and a broad variability with respect to component 1. For this reason it can serve as an ideal model reaction for the study of all relevant mechanistic details of a Diels-Alder reaction with inverse electron demand5). Although several aspects have been investigated by Gilchrist and coworkers6), not all of their results are conclusive (e.g. stereospecificity of the cycloaddition). For the anticipated synthetic use') of 1,2oxazines, however, full understanding of the mechanism is an indispensable prerequisite. In this paper we will deal with the stereospecificity, the exolendo and EIZ selectivity of nitroso alkenes as well as with the relative reactivity of silyl enol ethers 1, or other suitable olefins, towards 2. exolendo Selectivity of 3,CDihydro-1 -nitrosonaphthaleneIn an intramolecular nitroso alkene cycloaddition an endo-selective reaction has been reported (exo: endo = 1 : 3.4)8). To study this stereochemical feature in the geometrically less restricted intermolecular reaction we have employed 3,bdihydro-1 -nitrosonaphthalene (2a). This compound incorporates an E-nitroso alkene moiety and is generated from the bromo oxime 4a, which can easily be prepared from a-tetralone. 3a l a R = H l b CH3 Na2C03 2al \ (exo/endo > 97:3) 4a 3 b (exo/endo -64:36)Cycloaddition of 2a to trimethylsiloxy ethene (1 a) a...

Acid‐Induced and Reductive Transfor­mations of Enantiopure 3,6‐Dihydro‐2H‐1,2‐oxazines – Synthesis of Dideoxyamino Carbohydrate Derivatives

“…These reaction sequences lead to enantiopure pyrrolidines, azetidines, and amino‐substituted polyol derivatives or other interesting polyfunctionalized compounds. The synthetic potential of 2 H ‐1,2‐oxazines C thus nicely complements the chemistry of related 4 H ‐1,2‐oxazines6 and 6 H ‐1,2‐oxazines7 which were earlier investigated by our group. In this report we want to disclose the details of the acid‐induced reactions of 3,6‐dihydro‐2 H ‐1,2‐oxazines C .…”

7-Siloxy-Substituted Hexahydronaphthalene Derivatives: Samarium Diiodide Promoted Synthesis and Typical Reactions

“…Treatment of -bromo oxime 32 with base generated 3,3,3-trifluoro-2-nitrosopropene, 19 which slowly added to the electron-rich double bond of 21. This transformation required a large excess of the nitrosoalkene precursor (10 equiv), since additions to silyl enol ethers with substituents in the -position to the siloxy group are known to be less efficient; 20 the moderate yield of 35% for compound 33 was therefore not unexpected. The copper-catalyzed cyclopropanation of 21 was also not high yielding, but, with this reaction leading to siloxycyclopropane 34 in 31% yield, we could demonstrate that donor-acceptor cyclopropanes 21 of this type are also available from 7-siloxy-1,2,3,4,6,8ahexahydronaphthalene derivatives.…”

Conjugated nitrosoalkenes

“…Reissig et al 128 studied the relative reactivities of various alkenes in more detail. They used mainly trimethylsilyl ethers of enols and chose 1-nitroso-1-phenylethylene 1l as the model nitrosoalkene.…”

“…They used mainly trimethylsilyl ethers of enols and chose 1-nitroso-1-phenylethylene 1l as the model nitrosoalkene. 128 The following relative rate constants (k) were obtained for cycloaddition of various alkenes to 1-nitroso-1phenylethylene: 128 The rate constant (k) values presented above indicate that the EtO group possesses higher activating ability than the Me 3 SiO group. It is also noteworthy that the reactivity of 1,1-disubstituted trimethylsilyl enol ethers is much lower than that of 1,2-disubstituted derivatives.…”

“…120 The diastereoselectivity of cycloaddition of alkenes to 3,4dihydro-1-nitrosonaphthalene 88 has been studied. 128 It was found that trimethylsilyloxyethylene affords almost exclusively the exo-adduct. When there are one or two alkyl substituents at the double bond, the proportion of the endoadduct increases.…”