Methylenation using diazomethane

Methylenation using diazomethane, 2 78 Methylene, 29 303-304 Methylene blue, astatination, 31 77 Methylenephosphoranes, reaction with hexafluoroacetone, 30 258... 

An interesting report has been made of methylene insertion into the P-C linkage of a-(acyloxy)iminoalkylphosphonates derived from carbohydrates.181 This reaction system, using diazomethane, allows extension of the chain by a single carbon atom, with that atom (methylene group) attached directly to the phosphorus. 

It will now be shown that the discrepancy can be resolved by considering the possibility of a more energetic methylene in the experiments of Bell and Kistiakowsky, who used diazomethane photolysis to generate methylene. Frey41 has shown that methylene from diazomethane may be more energetic than methylene from ketene by 10-15 kcal. 

The reaction of ( + )-bulbocapnine methyl ether (42) with excess boron trichloride in methylene chloride containing 0.3% ethanol produces the catechol (43) together with the monophenol (44). However, with boron tribromide, it is the diphenol (45) which is produced. Both compounds (44) and (45) can be O-methylated with diazomethane to the dimethyl ether (46), and hydrolysis of (46) with dilute hydrochloric acid leads to (+)-corytuberine (47).43 Alternatively, methylation of (43), using diazomethane, affords (+)-corydine methyl ether (48). 

Photolysis (200-260 nm) of diazomethane (CH2N2) produces highly reactive methylene (rCHj), which can insert into primary, secondary, and tertiary C-H bonds of an alkane with almost equal ease, as well as undergo addition to double bonds. The eyclopropanation of alkenes can, however, be achieved by carrying out the photolytic decomposition of diazomethane in the presence of metal salts. Palladium(II) acetate has been reported to be a very effective catalyst for the eyclopropanation of alkenes using diazomethane vide infra). 

Whereas a small but significant selectivity of methylene in gas-phase reactions is well established, the evidence for liquid-phase reactions is less definitive. Studies using diazomethane , phenylcyclopropane , or 9,10-dihydro-9,10-methanophenanthrene as the CHg precursor have been interpreted as indicating random attack on primary, secondary and tertiary C H bonds. However, some results for the liquid phase indicate slight selectivity , and recent liquid-phase experiments with isopentane show even greater selectivity at the tertiary position than does singlet-methylene insertion in the gas phase. 

Two difficulties arise when using diazomethane to cyclopropanate double bonds. First, it is extremely toxic and explosive. A safer reagent would be more convenient for routine use. Second, methylene generated from diazomethane is so reactive that it inserts into C—H bonds as well as C=C bonds. In the reaction of propene with diazomethane-generated methylene, for example, several side products are formed. 

Introduction of a methylene group using diazomethane in ether produces metal—carbon bonds as foUows ... 

Olefins react less readily with boron trichloride than with diborane, many being polymerized, although boron trichloride adds to norbomadiene. The insertion of methylene units into B—bonds using diazomethane was discussed in Chapter 2. 

The hydroxythiophenes which exist predominantly as the thiolen-2-ones also show reactions characteristic of the enol form. They can be methylated at the oxygen with dimethyl sulfate of diazomethane and they can also be acylated. - - They also react as thio-lene-2-ones showing a reactive methylene group which can be condensed with benzaldehyde. The danger of using chemical reactivity data for drawing conclusion as to the physical state of these tautomerizable systems has been pointed out. ... 

Whereas the utility of these methods has been amply documented, they are limited in the structures they can provide because of their dependence on the diazoacetate functionality and its unique chemical properties. Transfer of a simple, unsubstituted methylene would allow access to a more general subset of chiral cyclopropanes. However, attempts to utilize simple diazo compounds, such as diazomethane, have never approached the high selectivities observed with the related diazoacetates (Scheme 3.2) [4]. Traditional strategies involving rhodium [3a,c], copper [ 3b, 5] and palladium have yet to provide a solution to this synthetic problem. The most promising results to date involve the use of zinc carbenoids albeit with selectivities less than those obtained using the diazoacetates. 

In the ease of very immatnre organie matter, or when the main research aim is to investigate polar fractions, a different analytical scheme may be applied (Figure 15.3). Prior to the fractionation, total concentrated extracts are treated with 14% BF3 in methanol or diazomethane in ether to esterify free carboxylic acids, and then they are snbjected to silica gel TLC using methylene chloride or a mixture of... 

Methylene transfer from diazomethane to olefinic and aromatic double bonds has traditionally been carried out with Cu(I) halides 24 However, other copper salts have occasionally been used. 

Sensitization, which can populate the triplet manifold, was used in a number of instances. Sensitization with benzophenone was used in the photolysis of diazomethane to generate triplet methylene. The triplet methylene thus produced, however, failed to abstract much hydrogen from alkanes (cyclohexene), but... 

Diazomethane has been used to transfer methylene with high diastereoselec-tivity to the carbonyl group of a series of jS-ketosulfoxides, (Rs)-jo-tolyl-S(0)-CHR—CO—CHj F3,Cl2, giving the corresponding epoxides." ... 

Samples of both fulvic and humic acids were suspended in methanol and methylated with diazomethane. Both H and spectra of the free acids were obtained, at 299.94 MHz and 75.42 MHz respectively, on a Varian XL-300 spectrometer having a Nicolet TT-100 PET accessory. Spectra were obtained in D2O, in a 12-mm tube, with deuterated TSP (sodium 3-(trimethylsilyl)propionate-, , 3,3- 4) added as internal reference. GC/MS of methylated acids was conducted on a Hewlett-Packard Model No 5995 GC/MS/DA system equipped with a fused silica capillary column (12 m x. 020 mm ID, Hewlett Packard) internally coated with crosslinked methylene silicone. Infrared spectra were obtained with solid samples dispersed in KBr pellets, by using a Beckman IR-33 spectrophotometer. The various absorption peaks in IR and NMR were interpreted conventionally (9-10). 

Amino-1,2,3-triazoles with a substituent at the 4-position have been prepared (i) from azides and active methylene nitriles (ii) from azides and ynamines (iii) from diazomethane and carbo-diimides (iv) from azides and 1,1-diaminoethenes and (v) from the rearrangement of 3-hydrazono-1,2,4-oxadiazoles. Among these, the first method, a regiospecific process, is the most versatile and convenient although it is suitable only for 5-NH2-substituted triazoles. Other methods are used to prepare 5-NHR , 5-NR R - and 5-NHCOR-substituted triazoles. Intramolecular cyclization of suitable precursors also gives 5-aminotriazoles. For example, a-imino-a-piperidyl phenylhydrazones (838), in the presence of copper acetate, give 5-piperidyl-triazoles (839) (Equation (85)) <94H(38)739>. 

The Simmons-Smith reaction " and its variants are widely used for the stereospecific synthesis of cyclopropane compounds. The methodology involves the use of copper-treated zinc metal (the zinc-copper couple) with diiodomethane to add methylene to a carbon-carbon double bond. Alternative use of diazomethane in catalytic reactions does not offer the same synthetic advantages and is usually avoided because of safety considerations. As significant as is the Simmons-Smith reaction for cyclopropane formation, its employment for organic synthesis was markedly advanced by the discovery that allylic and homoallylic hydroxyl groups accelerate and exert stereochemical control over cyclopropanation of alkenes (e.g, Eq. 21), and this acceleration has been explained by a transition state model... 

Methylene has been detected in the thermal decomposition of diazomethane by mirror removal using Te, Se, As, and Sb mirrors.111 Mirrors... 

Diazomethane. Although CH2N2 photolysis has been widely used as a methylene source, the reaction of CH2 with CH2N2 has received little attention. The quantum yield in the photochemical decomposition of CH2N2 is about four at both 4360 A. and 3650 A.96 The mechanism is believed to involve a short energy chain, in addition to the simple process... 

Diazoalkanes, in particular diazomethane, can efficiently transfer a methylene unit to olefinic double bonds via a metal catalysed process. The range of alkenes that may be used as substrates in this cyclopropanation is vast. The efficiency of the cyclopropanation of various types of alkenes can be very dependent upon the particular catalyst chosen for the reaction. 

CARBENE. The name quite generally used for the methylene radical, CH,. It is formed during a number of reactions. Thus the flash photochemical decomposition of ketene (CH2=C=0) has been shown to proceed in two stages. The first yields carbon monoxide and CHj. the latter then reacting with more ketene to form ethylene and carbon monoxide. Carbcne reacts by insertion into a C- H bond to form a C-CH, bond. Thus carbene generated from ketene reacts with propane to form, i-butane and isobutane. Carbene generated by pyrolysis uf diazomethane reacts with diethyl ether to form ethylpropyl ether and ethylisopropyl ether. 

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