Bicyclic alkenes

AUylic organoboranes react via cyclic transition states not only with aldehydes and ketones, but also with alkynes, aHenes, and electron-rich or strained alkenes. Bicyclic stmctures, which can be further transformed into boraadamantanes, are obtained from triaHyl- or tricrotylborane and alkynes (323,438,439). 

Bicyclic alkenes. Bicyclic systems like the alkene 5.123 are well known to be attacked from the exo direction, on the less hindered convex face of the bicyclic system. Similarly high levels of stereocontrol are found for... 

Bicyclic alkenes. Bicyclic systems like the alkenes 5.188 and 5.189 are well known to be attacked from the exo direction,600 601 on the less hindered convex face of the bicyclic system. Similarly high levels of stereocontrol are found for nucleophilic attack on bicyclic systems, as in the reduction of the ketone 5.190, in which the preference for exo attack overwhelms the steric hindrance offered by the adjacent methyl group.602 Bicyclic systems, especially like these with a zero bridge, are often used in synthesis to give reliably high levels of stereocontrol, with the penalty that there may be many steps needed to open them up to reveal a target structure. 

In contrast to the anti addition observed with acyclic and monocyclic alkenes, bicyclic alkenes frequently show syn addition. Norbornene gives exclusively exo-syn addition. Even 7,7-dimethylnorbornene gives the exo-syn product, in sharp contrast to the usual ent/o-directing effects of 7-substitution. These results are difficult to reconcile with a bridged mercurinium ion and suggest that intramolecular transfer of the nucleophile from mercury occurs. In norbornene derivatives, the competing anti addition is sterically restricted by the endo bridge. 

A major difficulty with the Diels-Alder reaction is its sensitivity to sterical hindrance. Tri- and tetrasubstituted olefins or dienes with bulky substituents at the terminal carbons react only very slowly. Therefore bicyclic compounds with polar reactions are more suitable for such target molecules, e.g. steroids. There exist, however, several exceptions, e. g. a reaction of a tetrasubstituted alkene with a 1,1-disubstituted diene to produce a cyclohexene intermediate containing three contiguous quaternary carbon atoms (S. Danishefsky, 1979). This reaction was assisted by large polarity differences between the electron rich diene and the electron deficient ene component. 

The silyl enol ethers 209 and 212 are considered to be sources of carbanions. and their transmetallation with Pd(OAc)2 forms the Pd enolate 210. or o.w-tt-allylpalladium, which undergoes the intramolecular alkene insertion and. 1-elimination to give 3-methylcyclopentenone (211) and a bicyclic system 213[199], Five- and six-membered rings can be prepared by this reaction[200]. Use of benzoquinone makes the reaction catalytic. The reaction has been used for syntheses of skeletons of natural products, such as the phyllocladine intermediate 214[201], capnellene[202], the stemodin intermediate 215[203] and hir-sutene [204]. 

Allylic carbonates are most reactive. Their carbonylation proceeds under mild conditions, namely at 50 C under 1-20 atm of CO. Facile exchange of CO2 with CO takes place[239]. The carbonylation of 2,7-octadienyl methyl carbonate (379) in MeOH affords the 3,8-nonadienoate 380 as expected, but carbonylation in AcOH produces the cyclized acid 381 and the bicyclic ketones 382 and 383 by the insertion of the internal alkene into Tr-allylpalladium before CO insertion[240] (see Section 2.11). The alkylidenesuccinate 385 is prepared in good yields by the carbonylation of the allylic carbonate 384 obtained by DABCO-mediated addition of aldehydes to acrylate. The E Z ratios are different depending on the substrates[241]. 

The geometry of bicyclic rings can also cause distortion of the alkene bond from coplanarity. An example is bicyclo[2.2.1]hept-l-ene ... 

The bicyclic product is formed by coupling of the two radical sites, while the alkene results from an intramolecular hydrogen-atom transfer. These reactions can be sensitized by aromatic ketones and quenched by typical triplet quenchers and are therefore believed to proceed via triplet excited states. 

The Boger pyridine synthesis involves the reaction of triazine 1 with activated alkene 2 in a hetero-Diels-Alder fashion. The intermediate bicyclic species 3 is unstable and a facile cycloreversion takes place due to the loss of nitrogen gas to afford the appropriately substituted pyridine derivative 4. 

The reaction with bicyclic alkenes—e.g. norbornadiene 8—preferentially yields the cxo-product 9 ... 

For example, Piers and Marais demonstrated that keto iodo alkene 32 can be converted to bicyclic keto alkene 35 in one pot21 (see Scheme 7). In this interesting methylenecyclopentane annulation method, it is presumed that intermediate 33, produced by sequential oxidative addition and deprotonation reactions, undergoes conver-... 

In an extension of this work, the Shibasaki group developed the novel transformation 48—>51 shown in Scheme 10.25c To rationalize this interesting structural change, it was proposed that oxidative addition of the vinyl triflate moiety in 48 to an asymmetric palladium ) catalyst generated under the indicated conditions affords the 16-electron Pd+ complex 49. Since the weakly bound triflate ligand can easily dissociate from the metal center, a silver salt is not needed. Insertion of the coordinated alkene into the vinyl C-Pd bond then affords a transitory 7t-allylpalladium complex 50 which is captured in a regio- and stereocontrolled fashion by acetate ion to give the optically active bicyclic diene 51 in 80% ee (89% yield). This catalytic asymmetric synthesis by a Heck cyclization/ anion capture process is the first of its kind. 

A method for the stereospecific synthesis of thiolane oxides involves the pyrolysis of derivatives of 5-t-butylsulfinylpentene (310), and is based on the thermal decomposition of dialkyl sulfoxides to alkenes and alkanesulfenic acids299 (equation 113). This reversible reaction proceeds by a concerted syn-intramolecular mechanism246,300 and thus facilitates the desired stereospecific synthesis301. The stereoelectronic requirements preclude the formation of the other possible isomer or the six-membered ring thiane oxide (equation 114). Bicyclic thiolane oxides can be prepared similarly from a cyclic alkene301. 

Non-heteroatom-stabilised Fischer carbene complexes also react with alkenes to give mixtures of olefin metathesis products and cyclopropane derivatives which are frequently the minor reaction products [19]. Furthermore, non-heteroatom-stabilised vinylcarbene complexes, generated in situ by reaction of an alkoxy- or aminocarbene complex with an alkyne, are able to react with different types of alkenes in an intramolecular or intermolecular process to produce bicyclic compounds containing a cyclopropane ring [20]. 

The resulting carbene complex 41b bears a hetero substituent and shows activity in the ring-opening/cross metathesis of strained bicyclic alkenes and... 

The 2-azadiene system of the pyrazinone scaffold undergoes inter- and intramolecular cycloaddition reactions with a variety of (functionalized) alkenes forming bicyclic adducts, leading to the stereoselective generation of a variety of natural product analogues as well as peptidomimetics [58]. These bicyclic compounds could serve as key intermediates in the synthesis... 

Under certain conditions, amides can add directly to alkenes to form N-alkylated amides. 3-Pentenamide was cyclized to 5-methyl-2-pyrrolidinone by treatment with trifluorosulfonic acid. Acylbydrazine derivatives also cyclized in the presence of hypervalent iodine reagents to give lactams. When a carbamate was treated with Bu3SnH, and AIBN, addition to an alkene led to a bicyclic lactam. 

---