Cycloaddition reactions bridged ring compounds

Thermal intramolecular cycloaddition reactions of unsaturated nitrones 1341 derived from a series of N- 2-alkenyl)-2-pyrrolecarbaldehydes 1340 and benzylhydroxylamine lead to competitive formation of two kinds of intramolecular cycloadducts, namely the fused- and the bridged-ring regioisomers 1342 and 1343, respectively (Scheme 255) <2001T8323>. Further elaboration of compounds 1342 and 1343 has given pyrrolizidine and indolizidine derivatives, respectively. A similar regiochemical trend was observed when aldehydes 1340 were reacted with (/ )-a-methylbenzylhydroxylamine in order to synthesize optically active compounds. 

Whilst the majority of the work described in this section involves the synthesis of cyclic phosphorus compounds, most of the chemistry could equally apply to arsenic and antimony and to a lesser extent bismuth. Most of the compounds synthesized have more than one heteroatom in the ring system, and not infrequently there are a number of heteroatoms, several of them often bound to the bridging metalloid atom, M. The methods most sucessfully applied to the synthesis of the parent and monoheterobicyclic compounds have been those involving addition and cycloaddition reactions. 

When phosphaalkynes are exposed to bis- and tris(diazo) compounds, bis- or tris(l,2,4-diazaphosphol-5-yl) compounds are formed that may be further converted into a variety of novel heterocyclic systems. For example, bis- and tris[diazo(tri-methylsilyl)methyl]phosphanes 237 and 240 afforded bis- and tris(diazaphospho-lyl)phosphanes 238 and 241 after cycloaddition with terf-butylphosphaacetylene followed by a subsequent 1,5-silyl shift (Scheme 8.56) (300). Reaction with electrophilic halides at the Wsilyl functions allows the introduction of a heteroatom bridge between the diazaphosphole ring leading to polycyclic ring systems such as 239 and 242. 

Reaction of triazolopyrimidinium ylides (256) with active acetylenes gave the 1 2 adducts 260. The formation of 260 may occur in two ways the shortest pathway consists of the double 1,3-dipolar cycloaddition of the diylide 256A with two molecules of the acetylene at two different sites to form the tetracyclic adduct 257, followed by ring opening under basic conditions to give 260. The second pathway consists of cycloaddition between the ylide carbanion of 256 and the bridged carbon C-4 to form the 1 1 adduct 258, which isomerizes to the more stable compound 259, which may be formed directly by the cycloaddition at the ylide carbanion and C-2. The second cycloaddition afforded the 1 2 adduct 257 [87JCS(P1)2531] (Scheme 49). 

Macro carbocyclic rings can be constructed by cyclization of nitrile oxides derived from oj-nitro-l-al-kenes (Scheme 22). If the intervening bridge is not longer than seven atoms, only fused bicyclic products are obtained. Thus, the nitrile oxide derived from nitro compound (75a) is cyclized in 44% yield to the 5,9-fused bicyclic isoxazoline (76a).38 10-Nitro-l-decene (75b) also cyclized to (76b) in unspecified yield.39 It should be noted that these results go counter to the usual regiochemistry of an intermolecular nitrile oxide cycloaddition where the five-substituted isoxazoline is usually,27 although not always,40 heavily preferred from reaction of a terminal alkene. Thus, geometric constraints have won out over the normal electronic control. 

Unique synthetic opportunities, particularly in alkaloid chemistry, are opened up on applying this protocol to diazo imides bearing a tethered heterocyclic ring. Thus, isomunchnone dipole, which is derived from these compounds, undergoes intramolecular cycloaddition across the heterocyclic CT-bond to produce bridged polyfused systems. Some examples of reactions with 2-furyl- and 1-indolyl-substituted substrates are shown in Schemes... 

Methyl 2-azabicyclo[3.1 -0]hex-3-ene-2-carboxylate (4) also reacts according to a [4+6] cycloaddition mechanism if tropone (26) is used as the electron-deficient triene. The primary product 27 of this [(27t-l-2ff)-l-(27t-f-27r + 27r)] process, containing a doubly bridged 11-membered ring, could not be isolated and immediately underwent an intramolecular Diels-Alder reaction to form the cage compound 28. ... 

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