Ring expansion, with diazomethane

Some straightforward, efficient cyclopentanellation procedures were developed recently. Addition of a malonic ester anion to a cyclopropane-1,1-dicarboxylic ester followed by a Dieckmann condensation (S. Danishefsky, 1974) or addition of iJ-ketoester anions to a (l-phenylthiocyclopropyl)phosphonium cation followed by intramolecular Wittig reaction (J.P, Marino. 1975) produced cyclopentanones. Another procedure starts with a (2 + 21-cycloaddition of dichloroketene to alkenes followed by regioselective ring expansion with diazomethane. The resulting 2,2-dichlorocyclopentanones can be converted to a large variety of cyclopentane derivatives (A.E. Greene. 1979 J.-P. Deprds, 1980). 

B. Flaherty, S. Nahar, W. G. Overend, and N. R. Williams, Branched-chain sugars. XIV. Reactions of glycosulose derivatives with diazomethane. Ring expansion of glycosulose derivatives, J. Chem. Soc., Perkin Trans. I (1973) 632-638. 

When the above-mentioned ring expansion with diazomethane 74) of trimethyl-dioxo[2.2]metacyclophane 65 (methylation was necessary to increase the inversion barrier to > 130 kJ) was performed in the presence of optically active alcohols at —60 °C, asymmetric induction occurred to an extent of ca. 40% ee (enantiomeric excess as determined by nmr-spectroscopy in the presence of chiral shift reagents)85). (+)-DibutyI tartrate favoured the dextrorotatory diketone 66 ([a]D 160° for the optically pure product) — the isomeric 67 was formed only with 3% ee (—)-ethyl lactate on the other hand led to an excess of (+)-67 ([a]D +240°) but gave (+)-66 with only 10% ee85). 

Cyclopentanone annelation. a,a-Dichlorocyclopentanones, obtained by addition of dichlorokctcnc to cycloalkcnes followed by ring expansion with diazomethane (9, 133-134), are versatile intermediates to a variety of interesting products. Some of the transformations are indicated in Scheme (I) and equation (I).1... 

OL-Methylenecyclohutanones. The reagent reacts regioselectively with activated alkenes (vinyl ethers, silyl enol ethers) to give cyclobutanones. These products undergo ring expansion with diazomethane to cyclopentanones. Both products undergo desilylative elimination in the presence of fluoride ion to form a-methylene ketones. 

A recent example of the preparation of a silylated and germylated cyclopropanone has been provided by Russian workers who added diazomethane in ether or methylene chloride at —130 °C to an equimolar amount of trimethylsilyl and trimethylgermylketene. The authors were able to obtain PMR spectra of the parent ketones which show an ABC system of cyclopropane ring protons at 0.8-1.8 ppm. These products react with methanol to form hemiketals and undergo ring expansion with excess diazomethane to form the corresponding cyclobutanone derivatives. 

The azepino-indole (600 E = COjMe) is produced by thermolysis of methyl 2-azidodiphenylmethane4 -carboxylate, N3C6H4CH2C6H4C02Me. Treatment of the pyrrolo-azepine (601) with benzoylmethylenetriphenyl-phosphorane, PhCOCH=PPh3, yields the bridged compound (602) by successive Michael addition and intramolecular Wittig reaction The imidazo-azepine (604) is formed from (603) by ring-expansion with diazomethane.Addition of dimethyl acetylenedicarboxylate to the cyclo-... 

Cyclodihydrocodeinone, on catalytic reduction, yields 14-methyl-C-nordihydrocodeinone (144), which, on ring expansion with diazomethane, yields 14-methyldihydrocodeinone and the related 6-spiro-oxiran, together with the corresponding seven-membered ring products of further expansion. ... 

With diazomethane ring-expansion takes place [134]. 

Subsequent preparations have used tetrahydronaphthalene itself as starting material but employed different modes of ring-expansion to obtain the dihydroheptalenes [195,196]. Dihydroheptalenes have also been obtained from 1,6-methano[10]annulene by ring-expansion with diazomethane, followed by thermolysis of the resultant 1,6-methano-cycloundecapentaene [197],... 

Kametani s group has applied the diazomethane ring expansion reaction of 3,4-dihydroisoquinoline methiodides to the preparation of isopavines. The carbon insertion reaction with the 3-aryl-3,4-dihydroisoquinoline methiodide 13 supplied a crude aziridinium iodide which upon standing in 6N hydrochloric acid for a week underwent successive ring expansion and closure, probably through the quinone methide 14, to furnish reframidine in 20% yield from the aziridine salt ... 

Hyperflorin, an antibiotic isolated from St. John s wort Hypericum perforatum L.), has been found on the basis of chemical and spectroscopic evidence to possess structure (639). ° A review on the conformational analysis of bicyclo[3,3,l]nonanes has appeared,and the conformations of l,5-disubstituted-3,7-dimethyIenebicyclo-[3,3,l]nonane derivatives have been shown, on the basis of lanthanide-induced n.m.r. shifts, to be predominantly in the double-chair form. In a notable paper that contains a wealth of information pertinent to adamantane synthesis, it has been reported that bicyclo[3,3,l]nonane-3,7-dicarboxylic acid, its dimethyl ester, and various derivatives exist mainly in the chair-boat conformation. The synthetic entry to these systems is illustrated for the above diester (643) in which the starting point is adamantanone (640) thus, ring expansion with diazomethane followed by SeOj oxidation gave the a-diketone (641) which was cleaved with periodate to give the diacid (642). Esterification using diazomethane gave (643) which exists, as does the diacid, as... 

Solvolytk ring-expansion to give a bicyclo[4,l,l]octan-3-one (Scheme 18) and ring-expansion with diazomethane to give ketones in the bicyclo[4,2,l]-nonane and bicyclo[5,2,l]decane series are reported. 

Meakins and Morris recently reinvestigated the reaction of 5a-cholestan-3-one (lb) with an excess of diazomethane and observed the same results reported by Nelson and Schut. Using preformed diazomethane in ether-methanol, Meakins and Morris found the reaction very slow. However, in the presence of potassium hydroxide, ring expansion proceeds smoothly. The role of the base in markedly increasing the reaction rate has not been explained. 

The lifetime of the diazomethane adduct is not known, but it must be of sufficient length that carbon can compete with nitrogen in participation as a nitrogen molecule leaves (24,109). The reaction of 66 with diazoethane yields 72, the normal adduct, and 73, the product from ring expansion. The structure of 73 was determined by hydrolysis to 2-methylcyclo-heptanone. In a similar reaction 74 yields 67 directly without isolation of 66. A similar ring expansion has been observed for cyclooctanone derivatives (16). 

Cyclic hydroxamic acids and V-hydroxyimides are sufficiently acidic to be (9-methylated with diazomethane, although caution is necessary because complex secondary reactions may occur. N-Hydroxyisatin (105) reacted with diazomethane in acetone to give the products of ring expansion and further methylation (131, R = H or CH3). The benzalphthalimidine system (132) could not be methylated satisfactorily with diazomethane, but the V-methoxy compound was readil3 obtained by alkylation with methyl iodide and potassium carbonate in acetone. In the pyridine series, 1-benzyl-oxy and l-allyloxy-2-pyridones were formed by thermal isomeriza-tion of the corresponding 2-alkyloxypyridine V-oxides at 100°. 

The reactions of diazomethane with heterocycles containing a ketonic grouping in the ring do not differ, in principle, from those of alicyclic ketones (see footnotes 3 and 177) ring expansion and the formation of epoxides compete. In general, ring expansion is the more important reaction for example, tetrahydropyran-4-one (99) is converted to l-oxacycloheptan-4-one (100) (60%) and 4,4 -epoxy-4-methyltetrahydropyran (101) (23%). ... 

Thianaphtheneqiiinone - (109) and diazomethane give a different reaction from that found with isatin, A -methylisatin and coumarandione. In as far as crystalline products could be isolated, the ring expansion occurs here between the sulfur and the carbonyl group in the 2-position. Depending on the solvent, there are formed 3-hydroxy-thiochromone (110), its 0-methyl derivative (111), or (presumably by attack on the 3-keto group of the tautomeric 3,4-diketo form of 110), 3,3 -epoxy-3-methylthiochromone (108). 

If the carbonyl grou]) in the 3-position of N-methylisatin or tlii-ana])hthencquinone is blocked by formation of an oxime (cf. 112), A -methylation of the oxime group occurs instead of ring expansion on reaction with diazomethane. In methanol, thianaphthenequinone oxime iV-mcthyl ether (113) then undergoes ring opening catalyzed by diazoniethane (113 114). 

The well-known reaction leading to ring expansion of cyclic ketones has been applied to derivatives of oxo sugars in an attempt to develop a new route to novel deoxy sugars. By treatment with diazomethane both a five-membered (42) and a six-membered (26) sugar ring have been expanded by insertion of a methylene group. 

Treatment of a cyclic ketone with diazomethane is a method for accomplishing a ring-expansion reaction. For example, treatment of cyclohexanone with diazomethane yields cycloheptanone. Propose a mechanism. 

Cyelobutanone has been prepared by (1) reaction of diazomethane with ketene,4 (2) treatment of methylenecyclobutane with performic acid, followed by cleavage of the resulting glycol with lead tetraacetate,s (3) ozonolysis of methylenecyclobutane, (4) epoxidation of methylene-cyclopropane followed by acid-catalyzed ring expansion,7 and (5) oxidative cleavage of cyclobutane trimethylene thioketal, which in turn is prepared from 2-(co-chloropropyl)-l,3-dithiane.8... 

Cyclooctanone has been prepared by distilling the calcium and thorium salts of azelaic acid, by heating azelaic acid with barium oxide in the presence of iron, by the action of nitrous acid on l-(aminomethyl)-cycloheptanol, by Dieckman cyclization of azelaic acid dimethyl ester and diethyl ester, and by ring expansion of cycloheptanone with diazomethane. ... 

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