Bicyclo heptanes isomerization

Effects of similar magnitudes have been observed in stereoisomeric cyclohexanes with oxygen functions, e.g., in l-fm-butyl-4-methoxycyclohexane. In the isomeric bicyclo[2.2.1]heptan-2-ols the 170-chemical shift difference is even larger63. 

For substituted tricyclo[4.1.0.02,7]heptanes, similar addition of benzenethiol in diethyl ether gave an isomeric mixture of bicyclo[3.1.1]heptanes.35 As shown in the mechanistic scheme, the 1,3-disubstituted patterns of the bicyclo[3.1, l]heptanes are governed by the regiospecific attack of the thiol radical on the sterieally less hindered bridgehead carbon. The results of these radical additions arc summarized for bicyclo[n.l.l]alkanes (Table 8)35 and bicyclo[1.1.0]butanes (Table 9). 

Acetylcyclohexanes isomerize to bicyclo[3.1.l]heptan-6-ols3 while 1 -acetyl-2-methylcyclohex-anes afford bicyclo[4.2.0]octan-7-ols4 as illustrated in the two examples below. 

Recently, Rooney and co-workers (23,58,59) have questioned the view that triadsorption by loss of 3 hydrogen atoms from the alkane is the minimum requirement for bond-shift reactions. They studied the isomerization of a series of caged hydrocarbons in excess hydrogen on palladium and platinum catalysts. The compounds were chosen in order to render difficult or totally exclude a mechanism involving aory-triadsorbed species. Thus, l,7,7-trimethyl[2,2,l]-heptane interconverts with its endo- and exo-2,3,3-trimethyl isomers, bicyclo-[3,2,2] octane changes to bicyclo[3,3,l] nonane, and protoadamantane to... 

In the absence of nucleophiles, the anti- and syn-5-methyl-bicyclo[2.1.0]heptanes 26 and 28 rearrange to the isomeric methylcyclopentenes 27 and 29 as major products under photo-ET conditions, although some crossover is detected for 28 (see Scheme 8) [74]. Matrix ESR studies show that bridging-bond stretched intermediate cations are formed, and that substituent shift from the middle carbon to form the... 

Bicyclo[4,l,0]heptanes.—The hydrogenation, hydroboration, thermolysis, amination, oxidation, and photochemical isomerization of various carane derivatives has been reviewed by Cocker. Another case of the repetition of earlier work has appeared, this time concerning the catalytic reduction of car-3-ene (307). Further work on the acid- and base-catalysed ring-opening of carene epoxides is reported (Scheme 17). ... 

An enantiomerically pure aldehyde, (lR,2R,3R)-2,7,7-trimethylbicyclo[3.1.1]hep-tane-2-aldehyde, is produced from a-pinene by rhodium-catalyzed hydroformylation [79, 80]. Initially, reaction with ferrocene under acidic conditions leads to a 1 1 mixture of diastereoisomeric cations, but on standing for a few hours at room temperature, isomerization by rotation around the ferrocene — cationic carbon bond to the thermodynamically more stable cation (with configuration (R) at the cationic center) occurs (Fig. 4-11). An enantiomerically pure amine is available by trapping of this cation by azide and reduction [75]. Analogously, the isomeric aldehyde with the bicyclo [2.2.1] heptane structure is formed by hydroformylation of a-pinene with cobalt catalysts [79, 80] and was used as the starting material for an isomeric series of chiral amines [75]. 

As expected, delocalizing substituents such as carbomethoxyl and cyano should decrease the barrier to inversion and perhaps may even convert the rapidly inverting g radical to a linear n radical. The net result should be a loss of configuration. Ando and coworkers have shown this to be the case in the tri-n-butyltin hydride reduction of the isomeric exo- (38) and n io-7-chloro-7-carbomethoxybicyclo[4.1.0]heptane (39). Both isomers gave the same (7 93) ratio of exo- (40) and emio-methyl bicyclo[4.1.0]heptane-7-carboxylate (41). 

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). 

Of the photochemical conversions of 3,6-bridged cyclohexa-1,4-dienes to 3,6-bridged syn-tricyclo[3.1.0.0 ]hexanes, the light-induced isomerization of norbornadienes to quadricyclanes (see Houben-Weyl, Vol.4/5a, pp 232-237) has been most intensively studied. The parent hydrocarbon, quadricyclane (1, tetracyclo[3.2.0.0 . 0 ]heptane) has become available on a preparative scale by acetophenone sensitized isomerization of norbornadiene (bicyclo [2.2.1]hepta-2,5-diene). ... 

Thus, treatment of (la,5a,7a)-bicyclo[3.2.0]heptane-l,7-diol with tosyl chloride in pyridine and rearrangement of the resulting monotosylate with one equivalent of potassium /erf-butoxide in tetrahydrofuran for ten minutes gave the tran.s-bicyclo[4.1.0]heptan-2-one trans-5) in 83% yield. When the reaction was allowed to proceed for 19 hours with two equivalents of potassium terf-butoxide, cw-bicyclo[4.1.0]heptan-2-one (cis-S) was isolated in 73% yield most likely this arises from initial formation and subsequent isomerization to the cis-ketone. When the rearrangement was run in deuterated teri-butyl alcohol the product contained less than 33 mol% of deuterium (17% -d, 14% 2-d and 2% 3-d) indicating that the rearrangement proceeds primarily without any kind of enolization. ... 

Efficient C-C bond formation took place when an isomeric mixture of 7-iodobicyclo[4.1.0]heptane was reacted with the stabilized carbanion of acetophenone.The reaction was photostimulated and occurred with a high degree of exo selectivity. Under the optimum conditions (bicyclo[4.1.0]hept-7-yl)acetophenone (14) was obtained in 87 % yield with an exojendo ratio of 16 1. The stabilized carbanions of 2-acetonaphthone and nitromethane reacted similarly, but the yields were below 45%. ... 

The reaction of bicyclo[4.1.0]heptane with diborane and subsequent treatment with hydrogen peroxide produced predominantly cyclohexylmethanol (5b) in high yield.Under modified experimental conditions small amounts of isomeric methylcyclohexanol (6b) and cycloheptanol (7b) were isolated. In contrast to the hydroboration of alkenes, the cyclopropane cleavage reaction is inhibited by ethereal solvents such as diethyl ether, tetrahydrofuran or 2-methoxy-ethyl ether. Bicyclo[3.1.0]hexane reacted with diborane in a similar fashion to give mainly cyclopentylmethanol (5a).The reaction of l-methylbicyclo[4.1.0]heptane gave a mixture of cis- and tram-(2-methylcyclohexyl)methanol (5c) in an initial ratio of 60 40. Spiro[2.5]octane reacted with diborane to yield only products derived from scission at the spiro carbon. The main product was 2-cyclohexylethanol (8). ... 

A mixture of o-menthanes resulted from reduction of o-cymene with Ca(NH3)6,297 and a neat route to the o-menthane skeleton involved photochemical addition of allene to 3-methylcyclohex-2-en-l-one and opening of the cyclobutyl ring with BF3.298 O-Menthadi- and tri-enes resulted from pyrolysis of verbenene.299 Acid-and base-promoted isomerizations of o-menthadienes300 and dehydration of cis- and trans- o-menthan-8-ols with a variety of reagents have been recorded.301 Optically active 2-methyl-4-isopropenylcyclohexanone (which is a useful precursor for ra-menthane derivatives) has been prepared by pyrolysis of chiral 2,2,5-trimethyl-bicyclo[3.1.1 ]heptan-2-one.302... 

Several natural products contain the norcarane (bicyclo[4.1.0]heptane) structure. The isomeric carenes arc comparatively inexpensive compounds occurring in almost enantiomerically pure form, but only as the (-r)-isomers [configuration (15)]. It is possible to convert ( + )-3-carene to ( + )-2-carene by base-induced isomerization31-38, without loss of optical purity. 

Precedence for this pathway comes from Wiberg s study of the thermal isomerization of tricyclo[4.1.0.0 ]heptane which gives bicyclo[3.2.0]hept-6-ene, which most reasonably is formed from cw,fran5-l,3-cycloheptadiene (Scheme 5.1) ... 

Paquette and Zon have reported detailed examination of the Ag" -catalysed isomerization of tricyclo[4,1,0,0 ]heptanes (350) to bicyclo[3,2,0]hept-6-enes (351). The reaction is highly stereo- and regio-selective with substituted derivatives, and evidently proceeds by an initial competitive attack of Ag" " on the b-c and c-d bonds of (350), followed by a 1,2-carbon shift. 

The carbenes derived from bicyclo[3,l,l]heptan-6-one and bicyclo[3,2,0]heptan-6-one by pyrolysis of their tosylhydrazone sodium salts, both rearrange to 6-methylene-bicyclo[3,l,0]heptane. A cyclobutylidene-methylenecyclopropane rearrangement of either carbene could give 1 -norcarene which could isomerize to the observed product. 

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