Heptane, tricyclic

The vicinal diol of the monoterpene series, (15,2S,3/ ,5S)-(+)-2,6,6-trimethylbicyclo [3.1.1]heptane-2,3-diol (1), was converted upon reaction with methyl dichloro-phosphite into a tricyclic phosphite 2 showing a 95 5 ratio of epimers differing at the phosphorus stereocentre (Scheme 1). Its complexes with Rh(I) and Pd(II) were found to have the structures (u-Cl)2[Rh(CO)L, and ris-CL,PdL2 respectively [16]. 

The three-component coupling systems explored extensively by Zhu has been used to synthesize tricyclic azaindole derivatives 153 from 150, heptanal 151, and an aryl- or alkylamine 152 (Equation 35) <20050L239>. 

Unfortunately, the situation is even more complicated In bi- and tricyclic compounds the a-SCS may experience further alterations apparently produced by intramolecular strain. The usually large a-SCS(CH3) in 1-methyl-bicyclo[2.2.1]heptane (9) (93) has already been mentioned. The a-effects of other substituents (OH, OCH3, Cl, I, and COOH) in the same molecular system do not correlate with those in bridgehead-substituted bicyclo[2.2.2]octanes or adamantanes again this was attributed to internal strain (125). The a-SCS(F)... 

These transformations were applied to develop a new promising method for synthesis of various bridged polycyclic systems66, viz. ketones 160 and 161. Tropone reacts with butenyl magnesium bromide (—78 °C, 75%) to form a mixture of 2-(3-butenyl)dihydrotropones 158 and 159, the pyrolysis of which (200-210 °C, neat or in heptane solution) leads to 60% total yield of the isomeric homoprotoadamantenones 160 and 161 and the tricyclic ketone 162 in a ratio of 58 18 24, respectively (equation 49)66. 

NMR measurements in the presence of lanthanide shift reagents are very popular when assigning bicyclo[2.2.1]heptanes, e.g., for 2-norbornanols and their methylated derivatives 591 597. The same is true for related tricyclic compounds such as derivatives of dicyclopen-tadienes598-600 1 and benzo-7-phosphanorbornenes601 2. 

If one of the C —C double bonds of the 1,6-diene is incorporated in or attached to a ring (e.g., cycloalkene, methylenecycloalkane) tricyclic compounds containing a bicyclo[3.2.0]heptane subunit are obtained as products. Thus, photobicyclization of monocyclic diallyl ethers or homoallyl vinyl ethers afford oxatricycloalkanes.6 Similarly, allylic alcohols containing an additional cycloalkenyl ring are converted to oxatricycloalkanes by irradiation in the presence of copper(I) trifluoromethanesulfonate as catalyst.9... 

Investigations into the solvolysis of a //-7-norbornenyl derivatives, and on the nature of the cationic intermediates involved,7 led to the conclusion that the bicyclo[2.2.1]hept-2-ene system is more stable than the tricyclo[4.1.0.03,7]heptane system.13,14 In terms of reactivity, the tricyclic derivatives surpass the bicyclic analogs by a large factor.15-17 For example, in 80% aqueous acetone containing dilute perchloric acid, 2-methoxytricyclo[4.1.0.03,7]heptane (3) is transformed quickly and quantitatively to u r/-bicyclo[2.2.1]hept-2-en-7-ol (4).18... 

We have found a rare reaction where two topochemical processes occur competitively in a single crystal, that is, a competitive photocyclo-dimerization and -polymerization in the crystal of 1,4-dicinnamoylbenzene 3 (15). On photoirradiation with a mercury lamp (100W) at 20°C for 9 h, the crystals of 3 (2.00g), dispersed in heptane (400 ml), are transformed into amorphous substances consisting of a tricyclic dimer, 21,22,23,24-tetraphenyl-1,4,11,14-tetraoxo-2 (3), 12 (13) -diethano(4,4Jparacyclophane, 4 (isolated yield 57%) (16), a mixture of oligomers (ca. 30%) and unreacted 3 (7%). 

By use of a similar method other more stable 1-substituted phosphiranes are prepared, 1-phenylphosphirane (123) being the most stable. When the cyclooctatetraene dianion is treated with dichlorophenylphosphine the bicyclic 1-phenylphosphirane derivative (124) is formed. At 70 °C in CHC13 it rearranges into the bicyclic phosphabicyclo[4.2.1]heptane derivative (125). Oxidation and photochemical reaction give the tricyclic phospholene 1-oxide derivative (126 equation (76)) (66JA3832). 

To the Co complex (1.28 g, 2.32 mmol) in heptane (23 mL, purged with carbon monoxide for 3 h before use) was added tri-n-butylphosphine oxide (506 mg, 2.32 mmol). The solution was sealed in a screw-cap resealable tub under an atmosphere of CO and heated to 85°C (over glyme heated at reflux) for 71 h. After cooling, the solution was applied directly to a bed of Fluorisil and eluted with ethyl acetate-petroleum ether 95 5 to 50 50) giving the tricyclic enone 304 mg, 45%) as a colorless oil [a]D 22 +116° (c 2.47, CHC13). 

Dihydrothiophene-1,1 -dioxide (2-sulfolene) (131) underwent a photochemical [2+2] cycloaddition with maleic anhydride to yield cycloadduct 132 which contained a m-fused cyclobutane (Scheme 36).83 Simple reactions of the anhydride function provided access to a wide range of novel bi- and tricyclic sulfones 133-135 containing the novel 2-thiabicyclo[3.2.0]heptane-2,2-dioxide ring system. 

Compound 1 did not react with unstimned internal olefins such as tetramethylethylene, /ra s-3-hexene, tram-stilbene, cyclooctene, cyclohexene, or cyclopentene. But imposing strain to the olefinic moiety resulted in a clean silylene transfer to the double bond Norbomene formed with 1 the tricyclic silacyclopropane 6. Whereas 2 did not add to the double bond of 7, methylene cyclopropane 8 could be transformed into spiro[2.2]pentane 9 by reaction with 1. Addition of 2 to bicyclopropylidene allowed the convenient synthesis of dispiro[2.0.2.1]heptane 10 in a quantitative manner. 

Cyclizations involving sulfenyl chlorides must be designed carefully, since these reagents can also react with alcohols, amines and other nucleophiles. Benzenesulfenyl chloride has been used to cyclize a 1,4-diene. For example, diene (4) cyclizes in good yield to tricyclic heptane product (5). This material was then further elaterated to a cyclosativene precursor (6 equation 4). ... 

The reduction of a series of bicyclic and tricyclic ketoximes using both Na-ethanol and LAH has been carried out and the product mixtures analyzed in detail. In this investigation it was found that reduction of the oximes derived from two tricyclo[2.2.1.0 ]heptan-3-ones (87) and (88) with either LAH-THF or Na-ethanol gave mixtures of exo (89) and (90) and endo (91) and (92) amines. Neither method of reduction was particularly stereoselective and the yields were somewhat better with LAH (87 76% versus 67% and 88 67% versus 44%). In contrast, reduction of the oximes of three bicyclo[2.2. l]heptan-2-ones (93)-(95) with LAH-THF gave significant quantities of azabicyclo[3.2.1]octanes (96)-(98) in addition... 

Similar procedures are also successful in the construction of cyclobutane rings in other stereochemical environments, including the formation of bicyclo[3.1.1]heptane (67)and bridged tricyclic systems such as (68), (69) ° and (70). ° A variety of annelated cyclobutanes have been prepared by the photochemical procedure as above, yields are sometimes poor or only moderate. Examples include bicy-clo[2.1.0]pentanes (71), °° bicyclo[2.2.0]hexanes (72)"° and cyclobuteno aromatics (e.g, 73), " o-nor-steroids e.g. 74)," A-bisnorsteroids" and triterpenes" as well as the highly strained tricyclo[4.2.0.0 ]octane system (75)," and the [4.4.4.5]fenestrane (76)." ... 

Under similar conditions, the 2-methylenebicyclo[2.2.1]heptane, or norcamphene (7) was conYerted to the isomer 6, through the intermediate formation of 5, whose maximum concentration in the mixtures is about 10%. This slow reaction is complicated by extensive hydrogen transfer and polymerization reactions (20), leading to saturated bicyclic hydrocarbons 2-methylbicyclo[2.2.1]heptane (12), bicyclo[3.2.1]- and [3.3.0]octanes (15 and 17). Isomerization of norcamphene (7) to hydrocarbons of the bicyclo[2.2.1]heptane series is also noticed at 250° in the vapor phase, but this is the main reaction at 140° in the liquid phase with the same catalyst. The main products are then 2-methyl-bicyclo[2.2.1]-2-heptene (8), l-methylbicydo[2.2.1]-2-heptene (10), and l-methyltricyclo[2.2.1.0]heptane 11 (13). The tricyclic isomer has been observed in the liquid-phase silica-alumina-catalyzed conversion of norbornene (21). 

Molecular orbital calculations have been performed for tricyclo[2.2.1]heptanes 10, and for their interaction with model acids and bases. It has been concluded that the bicyclo[2.2.1]hep-tadiyl diradical is in fact a stretched conformation of its collapsed fr-bonded tricyclic counterpart. ... 

When the reaction was peformed without an acid catalyst four products were formed, the tricyclic diamine 1 (23%), exo-5-morpholinobicyclico[2.2.1]heptan-2-one (1%), 2-mor-pholinobicyclo[2.2.1]hepta-2,5-diene (2%) and an enamine reduction product, enJo-2-mor-pholinobicyclo[2.2.1]hept-5-ene (3%). It has been shown that the yield of the tricyclic diamine increased as the reaction was extended. 

Allylic halogenation of aldehyde enol acetates, e.g. 23, derived from norbornadiene provided an elegant and efficient construction of the tricyclic structure 24 found in many sesquiterpenes such as cyclosativene, cyclocopacamphene, longicyclene, a-santalene and its derivatives. This rearrangement in fact arises from an electrophilic addition to a multiple bond with participation of the homoallylic bond. The tricyclic skeleton was also obtained successfully by treatment of 5-methylenenorborn-2-ene with A-bromosuccinimide in aqueous dimethyl sulfoxide which gave 5-bromo-2-hydroxymethyltricyclo[2.2.1.0 ]heptane (25) in high yield. 

The reduction of tricyclic compounds containing a bicyclo[4.1.0]heptan-3-one structure has been proved to be a rather general access to the spiroannulated cyclohexanone systems. 

A recent example of a ring opening based on the same principle is found in a series of synthetic studies toward taxol, in which model compound 251 has an oxabicyclo[2.2.1]heptane moiety derived from furfuryl alcohol as the precursor for ring-C of the target [200]. The hydroxymethyl group in 251 was converted to the iodide, and treatment with freshly activated zinc resulted in ring opening to the tricyclic system 252, Eq. 154. 

There are also X-ray structure determinations available for cyclic compounds containing an a-diazocarbonyl grouping. In 3-diazocamphor (3-diazo-l,7,7-trimethylbi-cyclo[2.2.1]heptan-2-one, 5.16 Cameron et al., 1972, iR = 0.056, a = 0.7 pm), the CO and NN distances and the CNN angle are in the range of values obtained with open chain a-diazo ketones. The CN distance (129.6 pm) is somewhat shorter. 5-Di-azo-6-methoxy-5,6-dihydrouracil (5.17) and its tricyclic derivative 2 -deoxy-5-diazo-6-hydro-0, 5 -cyclouridine were investigated by Abraham et al. (1971). The various interatomic distances are similar to those summarized above. Bond angles were not reported R = 0.056 and 0.052, respectively, a = <0.7 pm). 

The tricyclic skeleton analogous to that of 48 but with a five- instead of a four-membered ring, tricyclo[4.1.0.01,3]heptane, 52, is apparently much stabler than 48, as shown by the fact that 49 and other derivatives could be handled at room temperature [65], These authors also calculated (at the MP2/6-3IG level) strain energies and geometries of several similar tricyclic systems, including 53, 48, 52, and 54, using a group equivalents method ... 

Let us describe some frequently encountered polycyclic structures. Bicyclo[2.2.1] heptane, also known as norbomane, is the basic structure of a series of natural products. The tricyclic compound adamantane (tricyclo[3.3.1.L ]decane) is in principle the smallest structural fragment of diamond and its structure appears on the list of pharmaceutically important products. Adamantane was synthesized for the first time in 1941 at the University of Zagreb by Vladimir Prelog. 

Taylor and Paquette have used the acetone sensitized photochemical rearrangement of bicyclo[3,2,0]hept-6-ene-2-one to tricyclo[4,l,0,0 ]heptan-3-one in an improved synthesis of the derived tricyclic olefin. ... 

---