Bicyclo heptene derivatives

Askani, R Ober einige Bicyclo[4.2.0]octen- und Bicyclo[3.2.0]hepten-Derivate. Chem. Ber. 98, 2322 (1965). 

Many examples of polycyclic alkene osmylations have been reported in the literature in connection with the syntheses of specific target molecules such as alkaloids, prostanoids, or steroids. However, carefully determined diastereomer ratios are usually not available. Due to the varied nature of these substrates, it is not possible to formulate definite rules for diastereo-face differentiation except in specific cases. Thus, for example, the exclusive exo reactivity of bridged systems such as bicyclo[2.2.1]heptene derivatives (norbornene-type) is well known as Alder s rule of exo addition63. 

Cyclopentadiene is a very reactive diene and exists as its dimer that needs to be cracked (retro-Diels-Alder reaction) to prepare the diene. Cycloaddition with dienophiles forms bridged compounds of the bicyclo[2.2.1]heptane series. The reaction of cyclopentadiene with mono-and cw-disubstituted alkenes could give rise to two stereochemically distinct products, the endo- and ejco-bicyclo[2.2.1]heptene derivatives. It is found in practice, however, that the endo isomer predominates. 

A ready synthetic method for 2-alkyltropones uses the cycloaddition of a chloroketene to cyclopentadiene to give a bicyclo[3.2.0]heptene derivative which on treatment with sodium acetate provides the 2-alkyltropone [136] ... 

In addition it was also reported that compounds like bicyclo[2,2,l]-heptene derivatives react up to 30 times as fast as allyl ethers. Also, it was reported early that internal olefins exhibit lower reactivity than do the terminal ones. Cyclic olefins are claimed to be less reactive than terminal ones, however, Jacobine ei al, reported that resins functionalized with norbomenes react rapidly and exothermally in the thiol-ene reaction with multifunctional thiols due to ring strain ... 

The bicyclo[2.2.1]heptene derivative 2 , prepared via a Diels-Alder reaction by Samuelsson and Corey, is a selective inhibitor of the biosynthesis of PGEi (but not PGPia) from 8,U,lU-eicosatrienoic acid. This derivative bears obvious resemblance to the endoperoxide 30, a proposed Intermediate in prostaglandin Ei and F a biosynthesis ". ... 

Chao C-M, Beltrami D, Toullec PY, Michelet V (2009) Asymmetric Au(I)-catalyzed synthesis of bicyclo[4.1.0]heptene derivatives via a cycloisomerization process of... 

The above assumes that C protonation is not excluded for steric reasons. Thus N protonation takes place with derivatives of dehydroquinuclidine and the alkaloids neostrychnine and trimethylconkurchine (( ). N protonation was also believed to occur in the case of 2-N-hexamethyleneimino-bicyclo[l,2,2]-2-heptene, which was believed to give the nortricyclene derivative (6) on protonation with perchloric acid. Later work, however, showed the salt to be the results of C protonation (15) and to have structure 7. 

The enol ether double bond contained within the ds-fused dioxa-bicyclo[3.2.0]heptene photoadducts can also be oxidized, in a completely diastereoselective fashion, with mCPBA. Treatment of intermediate XXII, derived in one step from a Patemo-Buchi reaction between 3,4-dimethylfuran and benzaldehyde, with mCPBA results in the formation of intermediate XXIII. Once again, consecutive photocycloaddition and oxidation reactions furnish a highly oxygenated system that possesses five contiguous stereocenters, one of which is quaternary. Intermediate XXIII is particularly interesting because its constitution and its relative stereochemical relationships bear close homology to a portion of a natural product known as asteltoxin. 

Because aldrin contains the bicyclo-(2.2.1)-heptene ring structure, it reacts typically with phenyl azide to form a phenyldihydrotriazole derivative. This reaction is of importance in that it provides the basis for an analytical method for determining aldrin (discussed more fully in 2). 

Bicyclo[2.2.1]hepten-7-one is a useful intermediate in the synthesis of a variety of norbornane derivatives. The present procedure involves a four-step synthesis from hexachlorocyclo-pentadiene with a 39% overall yield. The next best method3 involves a four-step synthesis from norbornadiene with a 15% overall yield. 

Unusual amino acids include a class of unnatural a-amino acids such as phenylalanine, tyrosine, alanine, tryptophan, and glycine analogs, and f)-amino acid analogs containing 1,2,3,4-tetrahydroisoquinoline, tetraline, l,2,3,4-tetrahydro-2-carboline, cyclopentane, cyclohexane, cyclohexene, bicyclo[2.2.1]heptane or heptene skeletons. Different selectors were exploited for the separation of unusual amino acids, most of the production being made by Peter and coworkers teicoplanin [41, 56, 84, 90, 93, 124, 141-144], ristocetin A [33, 94, 145, 146], and TAG [56, 147]. Enantiomeric and diastereomeric separations of cyclic -substituted a-amino acids were reported by other authors on a teicoplanin CSP [88, 89], Ester and amide derivatives of tryptophan and phenylalanine were recently analyzed on a Me-TAG CSP [58],... 

An example of the vinylogous reactivity is the reaction of 52 with cyclopentadiene (Tab. 14.9) [77]. Rhodium(II) acetate-catalyzed decomposition of 52 in dichloro-methane, yields a 2 1 mixture of the bicyclic system 53 derived from the [3-1-4] cycloaddition, and the bicyclo[2.2.1]heptene 54 resulting from electrophihc attack at the vinylic position followed by ring closure. When Rh2(TFA)4 is used as the catalyst, bicy-clo[2.2.1]heptene 54 becomes the dominant product, while the reactivity of the vinyl terminus is suppressed using a hydrocarbon solvent as observed in the Rh2(OOct)4-cat-alyzed reaction in pentane, which affords a 50 1 ratio of products favoring the [3-1-4] cycloadduct 53. 

Several photochemically induced vinylcyclopropane to cyclopentene rearrangements of nor-carene derivatives to form bicyclo[3.2.0]heptenes can be understood as ring contractions of cyclohexenes to cyclobutanes. Upon direct irradiation of norcar-2-ene (bicyclo[4.1.0]hept-2-ene) at 214 nm (pentane solution), however, complex product mixtures were obtained containing only small amounts of bicyclo[3.2.0]hept-2-ene, while toluene sensitized photolysis in 50 millimolar solution in degassed pentane at 254 nm gave mainly the cyclobutane derivative 13 in addition to EjZ-isomeric hepla-l,3,6-trienes.72... 

Our further analysis of the enthalpy of formation of 2-methylbicyclo[2.2.1]heptene only worsens the disparity. That is, we find methylation of one doubly bonded carbon in gaseous cyclopropene, cyclopentene and cyclohexene is accompanied by a decrease in enthalpy of formation of 34, 38 and 38 kJmol-1, i.e. 36 2 kJmol-1. The recommended enthalpy of formation of bicyclo[2.2.1]heptene (see Reference 60) is 90 kJmol-1 and so we would predict an enthalpy of formation of its gaseous 2-methyl derivative of 90 — 36 54 kJmol-1. Using our standard enthalpy of vapourization estimation protocol we would predict a phase-change enthalpy of 40 kJmol-1 for this species, and so derive an enthalpy of formation of liquid 2-methylbicyclo[2.2.1]heptene of ca 54-40 15 kJmol-1. That is, if anything, the exocyclic species is too stable if we compare this derived value with 4.5 1.8 kJmol-1 derived from the available combustion calorimetric data. 

Disubstituted bicyclo 2.2.1 heptanes.2i Bicyclo[2.2.1]heptene is converted into 2,3-disubstituted derivatives when treated with an aryl or vinyl bromide and an alkyne in the presence of potassium acetate (1 equiv.) and a catalytic amount of Pd[P(C6H5)3LP Example ... 

Addition takes place at the nitrogen atom, because of steric factors, in derivatives of dehydroquinuclidine and some polycyclic alkaloids such as trimethylconkurchine, neostrychnine, etc.37 A curious formation of a nortricyclene derivative from 2-A-hexamethyIeneimino-bicyclo[l,2,2]-2-heptene (39) on treatment with perchloric acid199 has been claimed. 

Ring contraction of appropriately substituted 1,6-di- or tetrahalocycloheptatrienes or -cyclo-heptanones provides access to the bicyclo[4.1.0]heptene system. Thus l-bromo-6-chlorocyclo-hepta-l,3,5-triene reacted with butyllithium directly to alford benzocyclopropene (la) in 50% yield, presumably via a norcaradiene intermediate. The 2-methyl derivative lb was... 

Almost exclusively reported for 1-alkenylcarbenes and 1-alkynylcarbenes are examples dealing with mechanism-based and simple diastereoselectivity. The diastereofacial selectivity has been occasionally examined with bicyclo[2.2.1]heptene (norbornene) derivatives which provide the expected exo-adducts, while enantioselective [2 + 1] cycloadditions of these carbenes or their equivalents have apparently not yet been studied. 

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