Halogenation dienophiles

One of the early approaches to cyclic halogenated terpenes used the Diels-Alder reactions of (3-halogenated dienophiles, which enabled predetermined installation of the halogen functionality into the target architecture. This concept was first realized by Williard and de Laszlo who reported on a route to c/i/-plocamine 65 (Scheme 43.8). It has been demonstrated that the olefinic geometry of P-chloro dienophiles considerably affects the efficiency of the Diels-Alder reaction. Fortunately, (Z)-3-chloro-2-meth-ylpropenal 68 proved to be more reactive than the corresponding ( )-isomer toward various dienes to provide... 

For the ordinary Diels-Alder reaction the dienophile preferentially is of the electron-poor type electron-withdrawing substituents have a rate enhancing effect. Ethylene and simple alkenes are less reactive. Substituent Z in 2 can be e.g. CHO, COR, COOH, COOR, CN, Ar, NO2, halogen, C=C. Good dienophiles are for example maleic anhydride, acrolein, acrylonitrile, dehydrobenzene, tetracya-noethylene (TCNE), acetylene dicarboxylic esters. The diene preferentially is of the electron-rich type thus it should not bear an electron-withdrawing substituent. 

Z are CHO, COR,843 COOH, COOR, COCI, COAr, CN,844 NO,845 Ar, CH2OH, CH2C1, CH2NH2, CH2CN, CH2COOH, halogen, or C=C, In the last case, the dienophile is itself... 

The chemical reactivity of (1) and (2) is a dichotomy. Benzenoid character is indicated in normal electrophilic substitution (nitration, sulfonation and catalyzed halogenation, Section 4.26.4.1) and in the lack of dienophile reactivity in the Diels-Alder reaction. On the other hand, typical dienoid character is exhibited in the facile ozonolysis of the benzene ring of (1) and in the easy, non-catalyzed tetra-addition of halogen (see Section 4.26.4.1). 

Other current investigations concerning cycloadditions of nitrosoalkenes are directed towards employment of more complex dienophiles, e. g. NjM-bis-tri-methylsilyl enamines [380, 381] or 2,5-dihydrooxepines [382]. Furthermore, interest focuses on exploring the scope of subsequent reactions of the cycloadducts, such as stereoselective halogenation [383], ds-dihydroxylation [384] and numerous reductive [385] as well as acid or transition metal induced [386] transformations of 5,6-dihydro-4H-l,2-oxazines. 

Vinylbenzofurans, 3-vinylfuropyridines, and 3-vinylindoles can be prepared from readily accessible acetylenic precursors by halogen-lithium exchange, which triggers an addition on the triple bond followed by ethoxide elimination. Isomerization of an intermediate exocyclic allene provides a 1,3-diene system that can react in a [4-1-2] cycloaddition with electron-poor dienophiles (Equation 117) <20020L2791>. 

Following the key finding of Helmchen [23], the bis-(S)-ethyl lactate ester of fumaric acid was prepared from fumaryl chloride, as illustrated in Scheme 2. Cycloaddition of this dienophile with cyclopentadiene to give (3) required some experimental modification in order to eliminate halogenated solvents. A survey of solvents and reaction conditions revealed that triethylamine as solvent allows both a reasonable reaction rate and high diastereomeric excess (d.e. = 93%) when the reaction is conveniently conducted at room temperature. 

Metacyclophane (4a) also undergoes facile Diels-Alder reaction with weak dienophiles which did not react with la [66, 70]. Thus reaction of 4a with TCNE, DMAD, and MA furnished the [4 + 2] adducts 97a-c (Structures 18), respectively. Similarly, halogen substituted derivatives 4b-d (s. Scheme 9) gave the respective adducts 97d-j (Structures 18), though these were less reactive than the parent hydrocarbon 4a. This is ascribed to the electron-withdrawing effect of halogen substituents which lowers the HOMO level. 

These halogen derivatives have high functionality and are as equally reactive as levoglucosenone. They have been used as convenient Diels-Alder dienophiles in the Isobe synthesis of tetrodotoxin (53). 

---