Methylene derivatives formation

Addition of benzoyl chloride to 2.5-dimethyl-3,4,6-triphenyl-3//-azepine (13) in benzene in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) leads to elimination of hydrogen chloride and formation of the 2-methylene-l//-azcpine 14.117 All attempts to isomerize the methylene derivative to 1-benzoyl-2,5-dimethyl-3,4,6-triphenyl-l//-azepine under basic conditions failed. Analogous reactions can occur with 2,5-dielhyl-3,4,6-triphenyl-3//-azepine. 

The present procedure is applicable only to bromomalononitrile various a-halogen active methylene derivatives, (e.g., diethyl chloromalonate, methyl bromoacetoacetate) led predominantly to the formation of ring-contracted styrene derivatives. On the other hand, substituted cycloheptatrienylium salts with bromomalononitrile gave the desired dicyanoheptafulvene derivatives in excellent yields. One notable example is the synthesis of 5- and 7-(dicyanomethylene)-2,3-dihydrocyclohepta-1,4-dithiins.6... 

Plant sterols such as stigmasterol typically contain an extra ethyl group when compared with cholesterol. Now this is not introduced by an electrophilic ethylation process instead, two successive electrophilic methylation processes occur, both involving SAM as methyl donor. Indeed, it is a methylene derivative like that just seen in ergosterol formation that can act as the alkene for further electrophilic alkylation. After proton loss, the product has a side-chain with an ethylidene substituent the side-chains of the common plant sterols stigmasterol and sitosterol are then related by repeats of the reduction and dehydrogenation processes already seen in ergosterol formation. 

Methylene derivatives formed from alloxan can serve as bis-electrophiles and react with species such as guanidine to give pyrimido[4,5-tf pyrimidines directly (Equations 91 and 92). Formation of the Michael acceptor and the corresponding cyclization with thiourea can be carried out either in a single step (Equation 93) <2003RCB2457> or with isolation of the intermediate (Scheme 58) <2003SC3747> in either case, the process is reported to proceed most efficiently in the solid state under microwave irradiation. 

The thermochemical data are likewise sparse for the methylene derivatives of the bicyclic and polycyclic ketones. For these species, we consider the difference quantity <540 which is defined as the difference of the gas-phase enthalpies of formation of the ketone of interest and the related hydrocarbon ... 

Reaction of 9-[chloro(dimethylamino)methylene]tetrahydropyrido[l, 2-a]pyrimidin-4-ones 608 and aldimines or ketimines 609 in chloroform and acetonitrile gave a diastereomeric mixture of tricyclic compounds 611 and 612 at room temperature (82BEP892120, 82TL2891). The formation of compound 610 and the formation of a 1 1 mixture of the tricyclic products 611 and 612 could be detected by H NMR spectroscopy (82TL2891). After refluxing the reaction mixtures, only the thermodynamic product 611 could be isolated in pure form. 9-[Chloro(dimethylamino)methylene] derivatives 608 (R = CN, COOEt) also reacted with cyclic imines to yield the corresponding tetra- and pentacyclic quaternary salts, similar to 611 and 612 (87H2615). 

The 3-bromomethyl derivative (482), after anion formation at C-3, has the choice of the ring opening reaction as above or elimination of the bromide. The latter pathway is preferred, giving the 3-methylene derivative (483) which very readily isomerizes to its aromatic thiazole isomer (484) (81H(15)1349>. Similarly, the 2-bromomethyl derivative (485) on treatment with morpholine undergoes elimination to give the 2-methylene derivative, which with acid catalysis undergoes a prototropic shift to the 2-methyl thiazole (486) (74M882). 

A cortisone synthesis using remote functionalization at an unactivated carbon centre has been achieved.97 Cortexolone (224) was converted into the 5a-H,3j3-OH derivative (formation of the bismethylenedioxy-compound followed by lithium-ammonia-ethanol reduction). Inversion98 of 3)8- to 3 -OH followed by esterification with m-iodobenzoic acid produced (225), which on irradiation in methylene chloride containing phenyl iodide dichloride gave the 9 a -chloro-derivative (not isolated). This was dehydrohalogenated and saponified by methanolic potash to yield (226) (75%) and thence, by further known steps, cortisone acetate. 

The benzyl derivative (152) is deprotonated to the crystalline 1,2-dithiafulvene (153) by aqueous soda solution. The ease of formation and the stability of these 3-methylene derivatives are strongly influenced by the substituents.119... 

The approach employed for the preparation of nortriquinacene derivatives was based upon ring contraction of the a-diazocarbonyl derivative and subsequent degradation of the epimeric carboxyl derivatives (Scheme 67).393 All attempts to deprotonate hydrocarbon 445 have proven unsuccessful. Metal reduction studies on 444 and the related chlorides also failed to provide evidence for formation of a stabilized carbanion. Calculations agree with the absence of significant homoconjugation in 429. For example, this species is predicted to have a pyramidal rather than a trigonal anionic carbon.393 In addition, exo-methylene derivatives of nortri-... 

In the same vein, the primary event on broad-band UV-visible photolysis of matrix-isolated (CH3)4ReO and (53 R = Me) is elimination of CH4 and formation of methylene derivatives H2C=ReO(CH3)2 and H2C=Re(CH3)02, respectively. ... 

A Michael addition using the bifunctional reagent 289 was employed for the preparation of the bicyclic compound 290. The initially formed Michael adduct 291 undergoes intramolecular enolate alkylation to give the target compound. The employment of 289 as a substituted 2,4-Cf synthon in this sequence enables the formation of an ejco-methylene derivative, otherwise difficult to prepare. 

Six-membered acetal rings fused to seven-membered rings are found in acetals formed directly from mannitol and certain of its derivatives. The 1,3 2,5 4,6-structure has been proved for the tri-O-methylene " and tri-0-ethylidene " derivatives of mannitol, and the 1,3 2,5-structure for the di-O-methylene derivative of 6-deoxy-L-mannitol. " These acetals are markedly more stable than the 2,4 3,5-diacetals discussed above. Their stability has been related to the probable mechanism of formation,"" but is also understandable on conformational grounds. " The ring junctions are trans, and the triacetals LXI have the trans-anti-trans configuration, which... 

A variety of lactones and cycloalkanones have been converted into their 2-methylene derivatives using a one-pot procedure in which the key steps involve the formation of the corresponding thiophosphates (127) and their reactions with sodium borohydride under very mild conditions. This approach gives also ready access to racemic frullanolide in high yield and should be applicable to the synthesis of other endesmanolides. (An example of the synthesis of a-methylene lactones (128) is given in Scheme 31). ... 

The partial data presented above seem to indicate that substituents which are capable of stabilizing a carbocationic center at a bridgehead position will favor the formation of cyclobutyl derivatives, whereas such a substitution on the methylene carbons results in cyclopropylcarbinyl derivative formation. This is consistent with the observation that the acid-catalyzed methanolysis of 3-/ -bicyclobutanecarbonitrile (35) yields 58 % and 42 % of... 

As a general mle, unless an anion-stabilizing group, such as phenyl, or a heteroatom such as sulfur is present, the alkylsilane is not readily deprotonated. The a-halosilane can be deprotonated but, unlike the readily available chloromethyltrimethylsilane, there are few general methods to this approach. Al-kyllithium reagents add to vinylsilanes ( ) to produce the carbanion (287). Silyl derivatives with heteroatoms, such as sulfur, selenium, silicon or tin, in the a-position (288) may be transmetallated (Scheme 41). Besides the difficulty in synthesizing the anion, alkene formation lacks specificity for simple di- and tri-alkyl-substituted alkenes. As a result, the Peterson reaction of an a-silyl carbanion with a carbonyl has found the greatest utility in the synthesis of methylene derivatives, (as discussed in Section 3.1.3), heterosubstituted alkenes and a,p-unsaturated esters, aldehydes and nitriles. 

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