Bridgehead cycloadditions

Since diazaquinones are among the most powerful dienophiles, they undergo [4+2] cycloaddition (Diels-Alder) reactions with a great variety of dienes to give various heterocyclic systems accessible with difficulty by other methods. Diazaquinone reacts with butadiene and substituted butadienes, carbocyclic and heterocyclic dienes, 1-vinylcycloalkenes, polyaromatic compounds and vinylaromatic compounds to afford bicyclic and polycyclic bridgehead diaza systems, including diazasteroids (Scheme 56). 

Another interesting example is provided by the phenylethynylcarbene complex 173 and its reactions with five-, six-, and seven-membered cyclic enamines 174 to form bridgehead-substituted five-, six-, and seven-membered cycloalkane-annelated ethoxycyclopentadienes with high regioselectivity under mild reaction conditions (Scheme 38) [119,120]. In these transformations the phenylethynylcarbene complex 173 acts as a C3 building block in a formal [3+2] cycloaddition. Like in the Michael additions (reaction route F in Scheme 4), the cyclic electron-rich enamines 174 as nucleophiles attack the... 

The extensive study of Craig and coworkers [116] on the intramolecular Diels-Alder reactions of E- and Z-sulphonyl-substituted deca-, undeca- and dodecatrienes 120 (Figure 2.13) has opened a short route to trans- and cis-bridgehead hydrindanes and decalines and has given new insights into the role of dienophile substitution and geometry in determining the stereochemical outcome of these intramolecular cycloadditions. 

Similarly a marked increase of regioselectivity has been shown in the catalyzed Diels-Alder reactions of the chiral bicyclic lactame 24 (Scheme 3.9) with a variety of dienes [27] (isoprene, mircene, (E,E)-L4-dimethylbutadiene, 2,3-di-methylbutadiene, 2-siloxybutadiene). The catalyzed reactions were more regio-selective and totally enJo-antz-diastereoselective anti with respect to the bridgehead methyl group). The results of the cycloadditions with isoprene and mircene are reported in Scheme 3.9. The cycloadducts have then been used to provide interesting fused carbocycles [28] with high enantiomeric purity as shown in Scheme 3.10. 

P=C moiety in heterophospholes undergoes cycloaddition reactions with a variety of dienes and dipoles to afford a range of new heterocycles having bridgehead phosphorus atom [2, 4, 97, 98]. Previously, the reactivity of diazaphospholes towards cycloaddition reactions has been investigated to a limited extent [98],... 

In this chapter, synthesis, structure, and reactions of various classes of diazaphospholes have been reviewed. Recently used synthetic methods and variations for obtaining diversely substituted diazaphospholes have been discussed. On account of the cycloadditions on P=C bond of [1,4,2]- and [l,2,3]diazaphospholes, a number of organophos-phorus compounds incorporating a bridgehead phosphorus atom have become accessible. Recently reported complexation reactions of diazaphospholes, illustrate their capability to form transition metal complexes via different coordination modes. 

Lactam sulfonium salts bearing a dihydrothiopyran skeleton with a sulfonio bridgehead have been synthesized. Tricyclic benzothiazinium salts 87 were prepared by [4+2+]-polar cycloaddition of a thionium intermediate 99, generated from the corresponding a-chloro sulfide 98, in the presence of silver perchlorate in moderate to good yields (see Equation (28) and Table 17) <1997J(P1)309>. Cycloaddition with isoprene 41b gave adducts 87b and 87c as a... 

The impulse to the study of these cycloadditions came from the discovery that 5-spirocyclopropane isoxazolidines (or isoxazolines) undergo a thermal rearrangement resulting in the production of selectively substituted tetrahydro-(or dihydro) pyrid-4-ones (Scheme 42) [64], In particular, cyclic nitrones gave ultimately N-bridgehead bicyclic ketones, molecular skeleton of many alkaloid families [65]. 

Palladocyclopentadiene reagent promotes [2 + 2]-cycloaddition of suitably positioned enynes to form cyclobutenes which undergo symmetry allowed ring opening to form 1,3-dienes with a bridgehead double bond (equation 149)264. 

Similarly, in a 1,3-dipolar cycloaddition of DMAD to the conformationally locked cyclic a-alkoxycarbonylnitrone (727), bicyclic ring systems, containing a nitrogen atom at the bridgehead position have been synthesized. A mechanistic interpretation of the origin of the fused pyrroles (729) includes the intermediate formation of the aziridine ring in (728) (Scheme 2.303) (820). 

In another example (Scheme 8), the intramolecular cycloaddition of an azido functionality onto an enone group afforded bicyclic derivatives with bridgehead iV atoms. The cyclopentenone derivative 28 afforded the indolizidinone 30 through the proposed compound 29 which might react through a diradical intermediate or through a betaine intermediate <2002TL5385>. 

Tricyclic P-lactams not having a bridgehead nitrogen atom have been obtained by intramolecular Friedel-Crafls reactions <99T5567> and from the intramolecular Diels-Alder reactions of 1,3-dienes generated from a mesylate 79 <99TL1015>. Other tricyclic P-lactams e.g., 80 have been obtained by intramolecular nitrone-alkene cycloaddition <99TL5391>. 

Strained n/d/ -Bredt alkenes as well as -cycloalkenes will undergo [2 + 2] cycloadditions with alkenes. The bridgehead bicyclo[3.3.1]nonenones 16, produced as a transient species by the dehydrobromination of the corresponding bridgehead bromoketone, undergo cycloaddition with 1,1-dimethoxyethenc (15) to give the tricyclic ketones 17 in quantitative yields.7... 

On a similar note, a series of bridgehead alkenes and -cycloalkenes have been reported to undergo cycloadditions with l,l-dichloro-2,2-difluoroethene (12) to give the corresponding dichlorodifluorocyelobutanes.s... 

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