Bicyclo alkane derivatives

The other way to prepare cyclopropanes is based on the spin-center-shift. Thus, aryl-alkyl ketones, 26, bearing a leaving group X adjacent to the excited carbonyl group undergo a smooth cyclization to benzoylcyclopropanes 27 in moderate to good yields (Scheme 6b) [4a, b]. The reaction tolerates a variety of functional groups, often proceeds stereoselectively, and can be extended to the preparation of bicyclo[n.l.O]alkane derivatives. 

Termination by 2,2-disubstituted alkenyl groups can lead to bicyclo[n.l.O]alkane derivatives if the starting unit is an ortfto-snbstituted iodoaryl or a 1-haloalkenyl moiety (Scheme 31)."oi-t2i].[42]... 

A very interesting synthetic method of bicyclo[n.l.O]alkanes from cychc ketones via this 1,3-C,H insertion of magnesium carbenoid as a key reaction was reported (equation 22) . 1-Chlorovinyl p-tolyl sulfoxide (76) was synthesized from cyclopentadecanone and chloromethyl p-tolyl sulfoxide in three steps in high overall yield. Lithium enolate of tert-butyl acetate was added to 76 to give the adduct 77 in quantitative yield. a-Chlorosulfoxide (77) in a toluene solution was treated with i-PrMgCl in ether at —78 °C and the reaction mixture was slowly warmed to 0°C to afford the bicyclo[13.1.0]hexadecane derivative 79 in 96% yield through the reaction of the intermediate magnesium carbenoid 78. 

A substantial improvement in yield (84-96%) was achieved by using the O-trimethylsilyl derivatives of the above alcohols. DIB was superior in these oxidations to lead tetraacetate. It is noted that l-silyloxy-bicyclo[n.l.O]alkanes (n = 4-7) on treatment with iodosylbenzene-tetrabutylammonium fluoride were converted into mixtures of cyclic unsaturated ketones (Section 5.2.1). 

Substituted bicyclo[ . 1.0]alkanes may also be obtained by condensation of secondary amines with 2-haloketones. A variety of nucleophilic reactions can be carried out on the intermediate cyclopropaniminium salt 116251 (Scheme 108). Competing alkene scission and cyclopropanation occurs on reaction of enamines with pentacarbonyl-chromium carbene complexes252 (Scheme 109). N-Silylated allylamines and their derived N-silylated enamines undergo rhodium or copper catalysed cyclopropanation by methyl diazoacetate253 (Scheme 110). 

With bridgehead substituted bicyclo[4,2.0]alkanes, each pair of cis- or /ran.v-fused systems gives essentially the same ratio of products. Thus, solvolysis of cis- and m 5-l-(3,5-dinitrophenyl-methoxy)bicyclo[4.2.0]octane in 80% aqueous acetone buffered with 2,6-lutidine at 140°C and 100°C, respectively, gave the same mixture of spiro[2.5]octan-4-ol 14 and bicyclo[4.2.0]octan-l-ol 13 obtained from spirocyclopropylmethyl cation derivatives, suggesting one or more common intermediates. ... 

Bicyclo[n. 1.0]alkanes 22 with an endo leaving group X give allylic derivatives 24 of cw-cyclo-alkenes via c ,cw-allyl cations 23, regardless of the size of n and the experimental method [thermolysis, solvolysis, silver(I) assistance, deamination] used. In a secondary reaction HY is eliminated and c ,cw-1,3-cycloalkadienes are obtained. 

Photochlorination and photobromination of bicyclo[n.l.O]alkanes gave complex product mixtures containing 1,3-dihalides from substitution reactions, as well as products derived from abstraction of the a-hydrogens. 

It is not essential to use mono- or dihalocyclopropane derivatives. Ring expansion of methylene adducts, i.e. l-(trimethylsiloxy)bicyclo[n.l.O]alkanes 14, can be accomplished with a reagent consisting of iron(III) chloride in pyridine and dimethylformamide. In this process, p-chlorocycloalkanones 15 are the initial products of ring cleavage, but they are most conveniently converted to cycloalkanones 16 by refluxing with sodium acetate in methanol. ... 

Cycloalkenyl sulfides 10 are converted into bicyclo[n.2.0] alkane compounds with almost complete enantioselectivity by the reaction with the fumaric or acrylic acid derivatives 2a,c as listed in Scheme 8 and Table 3. As the reactivity of 10 is not as high as that of acyclic alkenyl sulfides, the use of an equimolar amount of the chiral titanium reagent is required to attain a good chemical yield in some cases. Diastereoselectivity is generally excellent and no ene product is detected. 

The mechanism of dehydrohalogenation under basic conditions of trons-fused bicyclo[4,n,0]alkane halohydrins (563)—(565) has been studied. Three reaction types are noted (i) epoxide formation, (ii) ketone formation, and (iii) ring contraction. trans-Diaxial chlorohydrins corresponding to (563)—(565) gave epoxides (566)—(568) with relative rates (derived from bimolecular rate constants) of 1 3 17. This rate sequence was rationalized in terms of deformation of the cyclohexane ring brought about by the nature of the fused ring. In particular, deformation is probably towards the half-chair conformation favoured by the cyclohexane epoxide which is formed in the slow step. trans-Diequatorial chlorohydrins represented by (563)—(565)... 

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