Propellanes rearrangement

Two illustrations that show the power of this reaction for the preparation of strained cycloalkenes are the contractions of 102 to the propellane 103 , an application that has been reviewed , and of 104 to the bicyclo[2.1.1]hexene 105 . The utility of the Ramberg-Backlund rearrangement in the preparation of various natural products such as steroids , terpenoids and pheromones has been demonstrated. In addition to the synthetic applications mentioned in the previous subsection, several selected examples taken from the recent literature are given in equations 66-69. These examples further demonstrate the potential of this method for alkene synthesis in general. 

In the abovementioned cases preparation of the propellanes was direct. A very nice instance exists, however, of rearrangement of a dispiran, 26, to Dewar benzenes 27 which happen to be [n.2.2]propelladienes. Silver ion (silver perchlorate at —20 °C) promotes the isomerization, as shown 10). 

Further, a very recent paper has reported a cascade rearrangement, under acidic conditions of the simpler educt, a dispiro[3.0.3.3]undecane derivative 93 to the dehydrated isomeric propellane 94 40). It is somewhat reminiscent of the analogous case of 26 where silver ion is the catalyst10). Treatment of the dispiro-alcohol 78 when heated for 2 hrs at 70 °C with p-toluenesulfonic acid in benzene gives in quantitative yield the [3.3.3]propellene 94. The following cascade is proposed to explain the rearrangement. 

Once we leave the realm of small-ring propellanes5 and post-1975 reports41,42 , it appears that it should be possible to convert suitably disposed sets of dispiran moieties into their respective propellane counterparts 39,40) because of the relative stabilities of the two families. By the same token, there are plenty of examples of acid-catalyzed rearrangement of propellanes, through which systems of yet greater stability may be obtained 5 41,42). 

When the ketone (280) was heated at reflux with pTsOH in benzene, the product (281) was isolated 95). The mechanism of this intriguing rearrangement may involve 1,3-hydride shift or epoxide formation 9S), This reaction appears to be an efficient method for the synthetis of [3.3.3]propellane. 

Amidst the complex mixture of products formed upon trifluoromethanesulfonic acid-catalyze skeletal rearrangement of tricyclo[6.2.I.0 Jundecane (478) has been found [3.3.3]propellane (479) and the methylated perhydrotriquinacene 4M and 481... 

The Wolff rearrangement has been very successfully used in the synthesis of propellanes.40 The highly strained 3-diazo[3,2.2]propellan-2-one was photolyzed in dichloromethane at — 70 °C in the presence of dimethylamine to give A W-dimethyl tricyclo[2.2.2.0 u4]octane-2-carboxamide (5), a very highly strained interesting compound with inverted geometry at the bridgehead carbons,42 in 40% yield.41... 

In the case of tricyclo[4.4.2.01-6]dodecan-2-one, acid-catalyzed rearrangement gave tricy-clo[4.3.3.01,6]dodecan-7-one (8), the propellane-like skeleton of which is otherwise difficult to construct synthetically. The reaction mechanism requires two consecutive Wagner-Meerwein... 

Coxon, Steel, and co-workers studied the transformations of a series of phenylalk-anols in fluorosulfuric acid at low temperature to find a variety of reaction modes. Cyclization of 2-phenylethanols, in most of the cases, is accompanied by rearrangement to afford various polycyclic products.319 The formation of propellane 86 was rationalized by the plausible mechanism shown in Eq. (5.123). 

There are numerous other examples of stereochemical correspondence in propeller molecules. The propellane 19> 1e has only one energetically reasonable isomerization mechanism available a twisting motion about the C3 axis which corresponds to the three-ring flip as well as to the trigonal twist rearrangement (Fig. 5). Similarly, only one isomerization mechanism (stereochemically correspondent in the permutational sense to the zero-ring flip) is energetically reasonable for tri-o-thymotide (Id). 8,20)... 

Trialkylboranes add to propellane to give a zwitterion that can rearrange to give 60 or react with another molecule of la to give 61. Both organoboron compounds were oxidized with hydrogen peroxide and isolated as the corresponding alcohols in 65% and 21% yield, respectively (equation 23). 

In the first approach shown in Scheme 9, ketoester 77 was alkylated successively with 4-bromobutene and 1,3-dibromopropene. After decarboxylation, 78 was converted into iV-aziridinylimine 79 in good yield. The pivotal radical cyclization reaction proceeded smoothly to produce a mixture of isomeric propellane compounds 80, which was purified after the epoxidation step. For the synthesis of modhephene, the mixture of epoxides was rearranged into the corresponding allylic alcohols 81 and then the allylic alcohols were oxidized, giving a separable mixture of unsaturated ketones 82a and 82b. The major product 82a possessed the correct stereochemistry of the methyl group of modhephene. Since 82a had already been converted into modhephene, a formal total synthesis of dZ-modhephene has thus been completed. The isomeric ratio of 80 reflects the stereoselectivity during the radical cyclization reaction. The selectivity was very close to the ratio reported by Sha in his radical cyclization reaction. ... 

Despite these modifications, Ireland s original method of both vinyl phosphate formation and reduction remains the most popular. In studies on the cationic rearrangements of [4.3.2]propellanes, Smith et converted a tricyclic ketone, via the diethyl vinylphosphate derivative, into the corresponding alkene (Scheme 26). In a similar manner, Kamata et al prepared A - and A -steroids (Scheme 27) with excellent control of regiochemistry. As shown in this example, esters are susceptible to cleavage under the standard reduction conditions (Li, NHa, Bu OH, -35 C), while acetals survive. 

It turns out that the [4.4.1]propellatetraene structure may be stabilized by proper (di) substitution at C (11). Thus the 11-methyl-11-cyano-, the 11,11-dicyano- (albeit unstable, rearranging to the dicyano-substituted benzocycloheptadiene), and the 11-benzyl-11-cyano-derivatives exist in the propellane form ... 

In the second instance, a meta-bridged-dichlorobenzene derivative (61) was prepared by rearrangement of the [5.3.1]propellane 60. ... 

The ultimate in small-ring propellanes (C2 exists but I don t consider it to be [O.O.OJpropellane), [I.l.ljpropellane (96), was finally synthesized from 2,3-dibromo-bicyclo[l.l.l]pentane (95) with t-BuLi . It undergoes thermal rearrangement to 97 with a half-life of 5 min at 114°C. Thus, Wiberg s prediction that this compound ought to be relatively stable as compared to other small-ring propellanes is amply borne out. In acetic acid it affords l-acetoxy-3-methylenecyclobutane (98). 

The Wagner-Meerwein rearrangement was one of the key steps in the total synthesis of (+)-quadrone by A.B. Smith and co-workers. The propellane substrate was treated with 40% sulfuric acid, which resulted in the [1,2]-alkyl shift of the initially formed cyclobutylcarbinyl system. 

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