Alkenes fused bicyclic

Grubbs and coworkers [238] used the ROM/RCM to prepare novel oxa- and aza-heterocyclic compounds, using their catalyst 6/3-15 (Scheme 6/3.9 see also Table 6/3.1). As an example, 6/3-35 gave 6/3-36, by which the more reactive terminal alkene moiety reacts first and the resulting alkylidene opens the five-membered ring. In a similar reaction, namely a domino enyne process, fused bicyclic ring systems were formed. In this case the catalyst also reacts preferentially with the terminal alkene moiety. 

The intramolecular cycloaddition of a silyl nitronate bearing a dipolarophilic appendage provides easy access to fused, bicyclic isoxazolidines (22). This process, in general, is very facile, and has allowed the use of unfunctionalized alkenes as dipolarophiles (Table 2.39) (106,124). Thus, a silyl nitronate bearing an allyl group will undergo the [3 + 2] cycloaddition at room temperature over 15 h to provide the corresponding isoxazoline upon acidic workup in moderate yield. 

A number of intramolecular cycloadditions of alkene-tethered nitrile oxides, where the double bond forms part of a ring, have been used for the synthesis of fused carbocyclic structures (18,74,266-271). The cycloadditions afford the cis-fused bicyclic products, and this stereochemical outcome does not depend on the substituents on the alkene or on the carbon chain. When cyclic olefins were used, the configuration of the products found could be rationalized in terms of the transition states described in Scheme 6.49 (18,74,266-271). In the transition state leading to the cis-fused heterocycle, the dipole is more easily aligned with the dipolarophile if the nitrile oxide adds to the face of the cycloolefin in which the tethering chain resides. In the trans transition state, considerable nonbonded interactions and strain would have to be overcome in order to achieve good parallel alignment of the dipole and dipolarophile (74,266). 

Pearson et al. (64) developed an approach to the fused bicyclic 3-pyrrolines 328 based on an intramolecular azide-alkene cycloaddition (Scheme 9.64). Azides (327) were heated at various temperamres between 70 and 110°C to afford the... 

Azaallyl anion cycloadditions. Imines bearing one or more aryl groups are converted by LDA into 2-azaallyl anions. These anions undergo cycloaddition not only with activated alkenes,2 but can also undergo intramolecular cycloaddition with a double bond to form as-fused bicyclic pyrrolidines.3... 

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. 

The 1,1-cycloaddition process also occurs in nonphotolytic reactions involving azomethine ylides. Thermolysis of oxazolinone (147) led to a 3,5-fused bicyclic dihydropyrrole in 80% yield.72 The alkene stereochemistry was maintained in the product, although subsequent photolysis scrambled the methyl and trideuteromethyl groups. Nondeuterated oxazolinone gave the cyclization product which was converted to a dihydropyridine on warming with acid.74... 

A number of tosylhydrazones containing an alkene have been shown to undergo intramolecular cycloaddition in the presence of acid.103 96 Boron trifluoride etherate appears to be the acid of choice.103 Bridged, rather than fused, bicyclic pyrazolines are formed under these conditions. The mechanism almost certainly involves cationic intermediates. Thus, tosylhydrazone (192a) cyclized in 87% yield to the... 

The intermolecular photocycloaddition of alkenes to cyclic enones was found to afford cis- and trans-fused bicyclic systems. This stereoselectivity and the diastereofacial selectivity of chiral alkenes and/or enones is discussed below. 

Selective conversion of acyclic dienynes to fused bicyclic rings containing five-, six- and seven-membered rings is efficiently catalysed by Ru complex 22. The reaction of dienyne 160 having two terminal alkene chains gave the two products 162 and 164... 

An azetidinone carrying vicinal alkene and alkyne groups, one of which may be an N-substituent, on the four-membered ring may be cyclized in the presence of a trisubstituted tin hydride at elevated temperature (Scheme 9) <1999JOC5377, 2003JOC3106>. In this way, the 1,4-disubstituted /3-lactams 303 were converted into the fused bicyclics 304 in moderate yield. 

This is the key to cis-fused bicyclic rings—everything happens on the outside (on the cover of the book). Nucleophiles add to carbonyl groups from the outside, enolates react with alkyl halides or Michael acceptors on the outside, and alkenes react with peroxyacids on the outside, Notice that this means the same side as the substituents at the ring junction. The rings are folded away from these substituents that are on the outside. 

Epoxidation is stereospecific and cis—both new C-0 bonds have to be on the same face of the old alkene. But Chapter 20 introduced you to several electrophilic additions to alkenes that were stereospecific and fra/rs, many of them proceeding through a bromonium ion. If stereospecific tram addition occurs on a c/s-fused bicyclic alkene, the electrophile will first add to the outside of the fold, and the nucleophile will then be forced to add from the inside. A telling example occurs when the 4/5 fused unsaturaled ketone below is treated with N -bromoacetamide in water. 

Reactions involving Monocyclic and Fused Bicyclic Alkenes Chemo- and Regio-selectivity... 

In the case of the cyclic substrate 51, the intervention of a C-H insertion pathway reveals itself in terms of the diastereoselectivity, not regioselectivity. Thus, exposure of enyne 51 to the standard Ru catalyst at ambient temperature produced the transfused bicyclo[5.4.0]undecene 52 (Equation 1.60, path a) [55]. If a metallacycle mechanism was operative, coordination of the metal with both the alkene and alkyne must occur to form the cis-fused product. On the other hand, coordination of the Ru with the Lewis basic bridgehead substituent directs it to abstract an allylic C-H on the same face as the substituent, which then leads to the trans-fused product as observed. On the other hand, cycloisomerization using a Pd(0) precatalyst does indeed lead to the Z-fused bicycle (Equation 1.60, path b). 

For A-acyliminium ions that (can) adopt the s-cis conformation, the mechanistic picture is quite different. Now the /V-acyliminium intermediate reacts as a 4ir-electron component in a Diels-Alder cycloaddition with inverse electron demand (equation 28). " This process also shows high regio- and stereo-selectivity in most cases. A nice illustration of high stereospecificity is found in recent work on the intramolecular Diels-Alder reaction of A-acyliminium species (equations 29 and 30). The bis-amides (50) and (51) serve as precursors to the reactive intermediates, which cycloadd to the alkenes with high selectivity to give r/a s-fused bicyclic 5,6-dihydro-1,3-oxazines. 

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