1-Bromo 2-,2-diphenylcyclopropane

Table 4 Stereochemistry of Grignard Reagent Formation from Optically Active 1-Methyl-1-bromo-2,2-diphenylcyclopropane...

B. l,l-Diphenyl-2-bromo-Z-acetoxy- -j>ropene. A 250-ml. flask equipped with a condenser is charged with 17.6 g. (0.050 mole) of 1,1-dibromo-2,2-diphenylcyclopropane, 12.5g. (0.075 mole) of silver acetate [Acetic acid, silver(l +) salt] (Note 4), and 50 ml. of glacial acetic acid, then immersed in an oil bath at 100-120° for 24 hours (Note 5). After cooling, the mixture is diluted with 200 ml. of ether and filtered. The ethereal filtrate is washed with two 100-ml. portions of water, two 100-ml. portions of aqueous saturated sodium carbonate, and finally with two 100-ml. portions of water. After drying over anhydrous sodium sulfate, the ether is removed on a rotary evaporator. Distillation of the resulting residue under reduced pressure yields 12.0 g. (72%) of the product, b.p. 142-145° (0.15 mm.), 1.6020-1.6023 (Note 6). 

Cathodic reduction of bicyclic gem-dibromocyclopropane in the presence of chlorotrimethylsilane provides the exo-silylated isomer selectively. With a sacrificial Mg anode the current efficiency can be increased by sonication as the anode acts additionally as a chemical reducing agent [358]. The 2e reduction of (5 )-(+)-l-bromo-l-carboxy-2,2-diphenylcyclopropane showed that the stereoselectivity at a Hg cathode was strongly determined by the supporting electrolyte cation. With NH4+, a preferential retention of configuration was observed, which increased with a more negative reduction potential. By contrast, a R4N+ cation gives rise to a major inversion, which increases with the bulkiness... 

In the reduction of (+) -1-bromo-l -metliyl-2,2-diphenylcyclopropane the intermediate cyclopropyl radicals are partially trapped by mercury to dicyclopropyl-mercury, which is subsequently reduced to the cyclopropanide ion. The configuration at Cl is only partially retained as the intermediate cyclopropyl radical... 

Further attempts to trap the chiral l-methyl-2,2-diphenylcyclopropyl radical, before inversion, by using excellent radical scavengers as solvents were also abortive. Decomposition of the diacyl peroxide (48) in thiophenol and reduction of (-)-(/ )- -bromo-l-methyl-2,2-diphenylcyclopropane (51) with tri-n-butyltin hydride as solvent resulted in essentially racemic hydrocarbon (49) ... 

Recently, Paquette and coworkers reported on the stereochemical consequences of having a trimethylsilyl substituent at the radical site. The Hunsdiecker reaction, as well as the Cristol-Firth modification thereof, on ( —)-(R)-l-trimethylsilyl-2,2-diphenyl-cyclopropanecarboxylic acid (71) resulted in racemic ( )-l-bromo-l-trimethylsilyl-2,2-diphenylcyclopropane (72). The trimethylsilyl group, bulky as it is, could not slow down the inversion frequency of the cyclopropyl a radical sufficiently to prevent complete racemization. More to the point, recentESR studies have demonstrated that the radical intermediate is planar, or nearly so. 

In 1961 it was reported that the reaction of chiral l-bromo-l-methyl-2,2-diphenylcyclopropane (51) with magnesium metal produced a partially optically active Grignard reagent . It was suggested that the racemization observed occurred in the Grignard formation step. In 1964 it was also established that the racemization occurred... 

Annino and his coworkers have postulated a mechanism for the reaction at the zinc surface patterned after the one proposed by Walborsky and coworkers for Grignard formation The organozinc intermediate formed is rapidly hydrolyzed by the protonic solvent. Note also that the reaction of zinc, in ethanol-10 % KOH, with chiral l-bromo-l-methyl-2,2-diphenylcyclopropane (51) yielded l-methyl-2,2-diphenylcyclopropane (49) with 21 % retention of configuration a result comparable to the 15% retention that is found in Grignard formation. 

An entirely different result has been reported by Jacobus and Pensak. They found that the reduction of the optically active 1-bromo-l-methyl-2,2-diphenylcyclopropane (51) with sodium naphthalenide (NaN) in DME (0.5 m) yields the corresponding hydrocarbon 49 of 29% optical purity with net retention of configuration. This observation was interpreted to mean that the l-methyl-2,2-diphenylcyclopropyl (t radical was being captured by a second SET from sodium naphthalenide to give the sodium derivative (which transforms in DME to 49) at a rate faster than its inversion frequency (Scheme 14). 

Walborsky and Rachon have also reported on the use of Rieke magnesium to obtain reaction with (S)-(+)-l-bromo-l-methyl-2,2-diphenylcyclopropane at —65°C to afford a chiral Grignard reagent that is 33-43% optically pure [73]. In 1961, Young and Walborsky [74] demonstrated that the reaction of chiral (S)-(+ )-l-bromo-l-methyl-2,2-diphenyl-cyclopropane (Table 5 1) with magnesium powder resulted in the formation of a chiral Grignard reagent as evidenced by the fact that on carbonation of the reaction mixture an optically active acid was obtained with an optical purity of approximately 12-18%. 

Reduction of (R)-(-f)-l-bromo-l-methyl-2,2-diphenylcyclopropane 18 with tri-n-butyltin hydride as solvent [18, 21] (Scheme 4). 

The first chiral halides used by Walborsky and Young [43,44] were optically active 1 -bromo-1 -methyl-2,2-diphenylcyclopropane 18, 1 -chloro-1 -methyl-2,2-diphenylcyclopropane 12, and I-iodo-l-methyl-2.2-diphenylcyclopropane 14, the absolute configurations and optical purities of which were established [40,49] as were those of their derivatives, l-methyl-2,2-diphenylcyclopropane 13 and l-methyl-2,2-diphenylcyclopropanecarboxylic acid 17. 

When (S)-( 4-)-l-bromo-l-methyl-2,2-diphenylcyclopropane 18 was treated with a powdered magnesium-magnesium bromide mixture in refluxing tetrahydrofuran and the reaction mixture carbonated (Scheme 11), the resulting products l-methyl-2,2-diphenylcyclopropanecarboxylic acid 17 and l-methyl-2,2-diphenylcyclopropane 13 were optically active, with predominant retention of configuration. This was the first... 

Table 7 Formation of Grignard Reagent from (4-)-l-Methyl-l-bromo-2,2-diphenylcyclopropane in Deuterated Ethers...

It is unreasonable to believe that a model that assumes that the radicals diffuse freely in solution could account for such results. On the other hand, a surface-bound radical is fully in accord with them. Compound (S)-(-l-)-18 behaves similarly when exposed to metal surfaces of alkali metals in hydroxylic solvents [94]. As in the Grignard reagent formation, when a solution of (S)-(-f)-l-bromo-l-methyl-2,2-diphenylcyclopropane 18 in methanol, isopropyl alcohol, or r-butenol was exposed to an alkali metal, such as lithium, sodium, or potassium, the resulting hydrocarbon (K)-( —)-l-methyl-2,2-diphenylcyclopropane 13 was shown to be optically active and with retained configuration, as shown in Table 19 and Scheme 40. 

A solution of 4.76 grams of 2,2-diphenylcyclopropane carboxylic acid, [a] —128°, in 40 ml. 0.75M KOH was added to a 0.15M solution of K3Co(CN)r,H in four portions over a period of 30 minutes. After an additional reaction time of 45 minutes, 90% of the acid, [a] —115°, was recovered. Optically active 1-bromo- and l-iodo-l-methyl-2,2-diphenyl-cyclopropanes (55) could not be reduced. 

Racemization. Optically active 1-bromo-l-methyl-2,2-diphenylcy-clopropane, l-iodo-l-methyl-2,2-diphenylcyclopropane, and l-bromo-2,2-diphenylcyclopropane carboxylic acid were prepared to study the mechanism of alkane formation by hydrido complex. While the first two substrates could not be reduced, the a-bromo acid absorbed 87 mole % of hydrogen, being converted into optically inactive acid (Reaction 18). A sample of the optically active acid retained its configuration under reaction conditions, indicating that a symmetrical intermediate was formed at some stage of the reduction. 

A solution of cis, fru .s-2,3-diphenylcyclopropylmagnesium bromide (70 ml, 6.1 mmol) is prepared from l-bromo-cA,/rans-2,3-diphenylcyclopropane (2.46 g, 9.0 mmol) and magnesium (2.46 g, 10.0 mmol) in diethyl ether (80 ml) and added at -10° to a suspension of /V.N-dimethyl-O-mesitylsulfonylhydroxylamine (1.50 g, 6.1 mmol) in THF (20 ml). The mixture is allowed to warm to 25° and stirred for 15 h. Hydrochloric acid (2 m, 20 mi) is added, and the aqueous layer is separated, extracted twice with ether, and basified (2 M NaOH, 20 ml). The resulting alkaline solution is extracted three times with ether. The extract is dried (MgS04), the solvent is evaporated, and the residue (880 mg, 52%) is recrystallized from ether/pentane to give 1-dimethylamino-cis,trans-2,3-diphenylcyclopropane (790 mg, 47%), m.p. 66-68°. 

Oxidative decarboxylation of optically active l-methyl-2,2-diphenylcyclopropanecarboxylic acid (10) with lead tetraacetate in the presence of iodine leads to racemized 1-iodo-l-methy 1-2,2-diphenylcyclopropane (11) in 45% yield. Subjecting 10 to the Cristol-Firth modification of the Hunsdiecker reaction (bromine and mercuric oxide in carbon tetrachloride) leads to racemic 1-bromo-l-methyl-2,2-diphenylcyclopropane (12) however, the yield is poor (5 /o). ... 

Reaction of ( —)-(5)-l-bromo-l-methyl-2,2-diphenylcyclopropane with iec-butyllithium followed by mercury(II) bromide gave (—)-bromo[(R)-l-methyl-2,2-diphenylcyclopropyl]mer-cury (3) in 37% yield. ... 

Addition of 1.0 M. s-BuLi in hexane to optically pure (—)-(S)-l-bromo-l-methyl-2,2-diphenylcyclopropane (4 g, 14 mmol) in dry EtjO (100 mL) over a period of 10 min at 0°C under argon gave a yellow solution. This mixture was stirred for 15 min and then added to a slurry of HgBrj (10.0 g, 27.7 mmol) in Et20 at 0 C. The addition required 30 min. The mixture was stirred for 4.5 h and allowed to come up to rt. The resulting reaction mixture was washed with HjO, dried, and evaporated to yield a solid residue which on crystallization twice (MeOH 75 mL) gave 2.17 g (37%) of the product mp 205-206°C. 

It seems likely that similar phenomena (partial retention) in similar reactions (electrochemical and MNaph reductions of l-bromo-l-mcthyl-2,2-diphenylcyclopropane) have similar explanations. If so. then RBr is an intermediate in both, as discussed earlier, and the a criterion fails. 

In their electrochemical. studies. Webb ei al. noted that the stereochemi.stry can be influenced by almost every parameter involved in the reaction. i.e.. solvent, electrolyte, electrode, leaving group (Br, 1, HgX), extent of reaction, and substituents at the reaction site (147]. Thus, reductions of l-bromo-l-methyl-2,2-diphenylcyclopropane in DMEi/tetra-n-butylammonium perchlorate give high yields of racemic RH. while similar reactions in acetonitrile and N. A-diniethylforniamidc give 25% retention. The presence or absence of iodide-ion also affects the optical purity of RM. 

Is it rational that racemic products result from the reaction of Ca(Naph)2 with I-bromo-1 -nielhyl-2,2-diphenylcyclopropane in THF at -78 C 1150. Perhaps. The change from partial retention (in reactions of alkali-metal naphthalenes) to racemization could be due to temperature (-78 C instead of 20°C) or the change in metal ion. Ca- might decrease the reducing power of the associated Naph , allowing step 6 or 8 to dominate (Scheme 7.1). 

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