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...

6‐Siloxy‐substituted 1,2‐oxazines 1 are transformed into 4‐hydroxy ketoximes 2 by reduction with NaBH4 in ethanol. Reductive Beckmann rearrangement converts the oxime 2a into the 1,4‐amino alcohol 7. Diisobutylaluminum hydride (DIBAH) induces a novel reductive ring contraction of 1 to provide either N‐hydroxypyrrolidine derivatives 8 or nitrones 9. Other 1,2‐oxazines lacking the 6‐siloxy substituent are also studied under these reaction conditions. Catalytic hydrogenolysis either gives the acyclic amine 16 or it stops at the stage of the proline derivative 21. Mechanistic features of these synthetically valuable transformations are discussed.

A variety of 5,6-dihydro-4H-1,2-oxazines 3 and 4 is prepared in good yields from silyl enol ethers 1 and nitroso alkenes 2a or 2b, respectively. A systematic variation of substituents reveals preparative scope and limitations of this hetero DielsAlder reaction with inverse electron demand. The cycloaddition is rather sensitive with regard to steric effects -in particular, large groups at C-1 of the silyl enol ethers 1 completely prevent the reaction. On the other hand, excellent diastereoselectivities are observed employing appropriately substituted olefins. The presented method for the synthesis of 1,2-oxazines also displays high regio-and periselectivity as is demonstrated by transformations l r -+ 3 r and 13-14.The chemistry of six-membered heterocycles exhibiting general structure A (1,2-oxazines) and incorporating an N -0 moiety is much less developed than that of the lower homologues (isoxazole derivatives). This is surprising since class A compounds might have interesting biological activities2' or other valuable properties. They can also display considerable synthetic potential as has been shown for 3,6-dihydro-2H-1,2-oxazines B by Kresze's group3). Synthesis and preparative use of 5,6-dihydro-4H-l,2-oxazinium salts C were advanced by Eschenmoser and coworkers4). A B C D E FIn this account and following papers we will deal with the chemistry of 5,6-dihydro-4H-1,2-oxazines D -from now abbreviated as 1,2-oxazines. Although single ld-oxazines can be prepared by cyclization of y-halogenated oximes, a retrosynthetic analysis shows that a [4 + 21 cycloaddition of olefins E and nitroso alkenes F should be a suitable and highly flexible route to heterocycles D. Indeed this approach was first realized by Bravo et al.') and was further developed by Viehe6) and mainly Gilchrist'! Their results') clearly demonstrate that this reaction can be classified as a Diels-Alder reaction with inverse electron demand9'.However, the potential of 1,2-oxazines D for (stereoselective) synthetic applications was not investigated in much detail''). We were intrigued by the attractive goal to prepare cyclic or acyclic 1,4-difunctionalized compounds G and H from D -as has been advanced with great success in the isoxazole field generating 1,3-difunctional systems 'I). Therefore we undertook a systematic study to explore scope and limitations of the [4 + 23 cycloaddition of nitroso alkenes F and the transformations of the resulting 1,2-oxazines D.

The 6-(trimethylsilyl)methyl-substituted 1,Zoxazine 1 can smoothly be deprotonated with n-butyllithium at C-4 to give a lithiated species which reacts with a variety of electrophiles to provide the new 1,2-oxazines 5 -16 in good yields. Besides the preparative aspect of these transformations, the high stereoselectivity of many reactions is also interesting from a mechanistic point of view. By deprotonation of the 4-deuterated compound 5a it has been proven that n-butyllithium removes exclusively the proton (or deuteron) cis to the 6-CH2SiMe3 group. Also, in most cases the reaction of lithiated 1 with electrophiles occurs with overall retention of configuration to afford preferentially cis-1,2-oxazines (series a). A mechanistic proposal for this highly stereoselective deprotonation process, which seems to be governed by the 1,2-oxazine oxygen, is discussed including a comparison with a recently reported ab initio calculation dealing with oxime ethers. Similar deprotonation/substitution reactions are described for l,2-oxazines 14, 2, 3, and 4. Possibly due to a differing carbanion structure a deviating behavior is observed in some cases. Several acidinduced and reductive ring-opening reactions of 1,6a, Ea, and 14a demonstrate the potential of 4-substituted 1,Zoxazines for the stereoselective synthesis of polyfunctionalized compounds.5,6-Dihydro-4H-l ,Zoxazines A (herein abbreviated as 1,2-oxazines) are heterocycles with a promising potential for the synthesis of polyfunctional compounds2). They can easily be prepared by the hetero-Diels-Alder reaction of electronrich olefins with nitroso alkenes as developed by Gilchrist and coworkers3). By use of silylated dienophiles we were able to extend the scope of this [4 + 21 cycloaddition considerably'). In this contribution we will include our results on the substitution of 1,2-oxazines A proceeding via the carbanion B to give heterocycles C which incorporate an electrophile El at C-4 and are not easily available otherwise.The analogous sequence is well-known for oxime ethers D5) or the related isoxazolines Eq. However, for the sixmembered heterocyclic system A we are only aware of Shatzmiller's reports dealing with compound F and the regioselectivity of its deprotonation'). We have examined the feasibility of the sequence A-+B-+C using the monocyclic 1,2-oxazines 1 and 2, and after having discovered the surprisingly high stereoselectivity we have extended our investigation to the bicyclic compounds 3 and 4. R = H4 R -SiMq

A variety of 6‐siloxy‐substituted 5,6‐dihydro‐4H‐1,2‐oxazines (abbreviation: 1,2‐oxazines) 1, 3 could be transformed into di‐ and trisubstituted pyrroles 2, 4 by means of molybdenum hexacarbonyl. The mechanism of this deoxygenating ring contraction is discussed. With two bicyclic 1,2‐oxazines an acid‐catalyzed fragmentation affording α‐methylenecycloalkanones 7 has been observed, while other 1,2‐oxazines rearrange in methanolic acid to give nitrones 9, 10. The desilylation of 6‐siloxy‐substituted 1,2‐oxazines 1, 3 employing NEt3 · 3 HF is a very general and smooth process providing 6‐hydroxy‐1,2‐oxazines 11, 12 or their corresponding acyclic tautomers 13, 14 in high yields. For two examples of 11 deoximations by use of formalin could be achieved with moderate efficiency giving 1,4‐dicarbonyl compounds 15.