Methylene transfer

Methylene transfer from lodomethylzmc iodide is stereospecific Substituents that were cis in the alkene remain cis m the cyclopropane... 

Methylene transfer from lodo methylzinc iodide converts alkenes to cyclopropanes The reaction is a stereo specific syn addition of a CH2 group to the double bond... 

Synthesis of terminal olefine from ketones or esters via a Ti methylene transfer reagent. 

Although steroidal spiro oxiranes are difficult to obtain stereochemically pure by peracid epoxidations of exocyclic methylenes,the recently developed methylene transfer reagents, dimethylsulfonium methylide and di-methylsulfoxonium methylide in tetrahydrofuran, proved useful in the stereoselective transformation of steroid ketones to a- and -oxiranes, (87) and (88), respectively. ... 

In a further extension of this reaction Winstein and Dauben showed that the action of the methylene-transfer reagent (1) on A -cycloal-kenols, e.g., (2), proceeds by stereospecific cis addition to give the cw-cyclo-propyl carbinol (5). It was also observed that both the rate and yield of the hydroxyl-assisted reaction are increased substantially. It has been suggested that the high stereoselectivity observed in these instances is best explained by complex formation or reaction of the reagent (1) with the hydroxyl group of (2) followed by intromolecular transfer of methylene. 

Epoxidation of aldehydes and ketones is the most profound utility of the Corey-Chaykovsky reaction. As noted in section 1.1.1, for an a,P-unsaturated carbonyl compound, 1 adds preferentially to the olefin to provide the cyclopropane derivative. On the other hand, the more reactive 2 generally undergoes the methylene transfer to the carbonyl, giving rise to the corresponding epoxide. For instance, treatment of P-ionone (26) with 2, derived from trimethylsulfonium chloride and NaOH in the presence of a phase-transfer catalyst Et4BnNCl, gave rise to vinyl epoxide 27 exclusively. ... 

Due to the high reactivity of sulfonium ylide 2 for a,P-unsaturated ketone substrates, it normally undergoes methylene transfer to the carbonyl to give the corresponding epoxides. However, cyclopropanation did take place when 1,1-diphenylethylene and ethyl cinnamate were treated with 2 to furnish cyclopropanes 53 and 54, respectively. 

Corey s ylide (1), as the methylene transfer reagent, has been utilized in ring expansion of epoxide 75 and arizidine 77 to provide the corresponding oxetane 76 and azetidine 78, respectively. 

Without question, the most powerful method for cyclopropane formation by methylene transfer is the well-known Simmons-Smith reaction [6]. In 1958, Simmons and Smith reported that the action of a zinc-copper couple on diiodomethane generates a species that can transform a wide variety of alkenes into the corresponding cyclopropanes (Scheme 3.3) [7]. 

The stereospecificity of the methylene transfer provides compelling support for a concerted mechanism and this conclusion has rarely been disputed. It is instructive, however, to review the experimental evidence that allowed for the elimination of the alternative mechanistic proposals, namely, a radical addition and a carbome-tallation (Scheme 3.4). 

The landmark report by Winstein et al. (Scheme 3.6) on the powerful accelerating and directing effect of a proximal hydroxyl group would become one of the most critical in the development of the Simmons-Smith cyclopropanation reactions [11]. A clear syw directing effect is observed, implying coordination of the reagent to the alcohol before methylene transfer. This characteristic served as the basis of subsequent developments for stereocontrolled reactions with many classes of chiral allylic cycloalkenols and indirectly for chiral auxiliaries and catalysts. A full understanding of this phenomenon would not only be informative, but it would have practical applications in the rationalization of asymmetric catalytic reactions. 

To resolve this problem, Rickborn made an ingenious proposal that implicated the intermediacy of a bimetallic transition structure assembly v involving a bridging Znl2 molecule (Fig. 3.5). This would accommodate the needed spatial requirements of the methylene transfer process. The importance of the polymetallic re-... 

The formulation of an additive for zinc carbenoid cyclopropanation that meets these criteria is severely compromised by the by the inherent Lewis acidity of the zinc atom. This Lewis acidity is required for methylene transfer and plays a major... 

IRC) analysis. It is found that the methylene transfer (path b) is significantly favored over the carbometallation (path a) by about 13 kcal mol . The good agreement between theory and experiment indicates that such studies are valid for this complex system. 

The next step in the calculations involves consideration of the allylic alcohol-carbe-noid complexes (Fig. 3.28). The simple alkoxide is represented by RT3. Coordination of this zinc alkoxide with any number of other molecules can be envisioned. The complexation of ZnCl2 to the oxygen of the alkoxide yields RT4. Due to the Lewis acidic nature of the zinc atom, dimerization of the zinc alkoxide cannot be ruled out. Hence, a simplified dimeric structure is represented in RTS. The remaining structures, RT6 and RT7 (Fig. 3.29), represent alternative zinc chloride complexes of RT3 differing from RT4. Analysis of the energetics of the cyclopropanation from each of these encounter complexes should yield information regarding the structure of the methylene transfer transition state. 

Examination of cyclopropanation through RT6 and RT7 reveals that a less conventional explanation may be required to rationalize the high reactivity of zinc car-benoids (Fig. 3.29). The structure of RT6 represents a pseudo-dimer as shown in RTS that has been further activated by coordination of zinc chloride to the oxygen of the chloromethylzinc alkoxide. This mode of activation is reminiscent of that observed in RTl. Cyclopropanation proceeding from RT6 through TS3 has an activation energy of 27.8 kcal mol . This represents a negligible decrease in the barrier to methylene transfer when compared to reaction from RTS. 

Whether these advances come from the study of zinc carbenoids, other organo-metallic sources, diazo precursors or as yet unrecognized sources of methylene transfer, it is our hope that this chapter will serve as a helpful starting point to guide future explorers of this fascinating landscape. 

Racemic 5-methyl-5 -(sodiomethyl)-A-(4-methylphenylsulfonyl)sulfoximine reacts with ketones to give an initial methylene transfer which produces an intermediate epoxide that is ring expanded to the oxctanc56. Application to 4-rerf-butylcyclohexanonc affords a single oxetane in 69% yield. While only achiral alkylidcne transfer reagents were utilized, in principle this reaction is amenable to the asymmetric synthesis of oxetanes. 

Several variations and extensions of this HHT method have recently been reported. The mildness of this reaction was exemplified through the synthesis of glyphosate thiol ester derivatives 35. The requisite thioglycinate HHT 34 was prepared in high yield by a novel, methylene-transfer reaction between r-butyl azomethine and the ethyl thioglycinate... 

D. L. Phillips, W.H. Fang, and X. Zheng, Isodiiodomethane is the methylene transfer agent in cyclopropanation reactions with olefins using ultraviolet photolysis of diiodomethane in solutions a density functional theory investigation of the reactions of isodiiodomethane, iodomethyl radical, and iodomethyl cation with ethylene. J. Am. Chem. Soc. 123(18), 4197-4203 (2001). 

Finally, it is worthwhile to note that the methylene-transfer pathway does not involve direct transfer of a CH2 group. An H atom migration pathway is a more accurate description of this pathway, given the experimental and theoretical evidence. 

Phosphaalkenes -P=C<, and phosphaimines -P=N- react with 1 to give secondary zirconated aminoalkyl or diamino phosphines, respectively, with P-coordination to the metal fragment (Scheme 8-24) [207]. An unexpected methylene-transfer reaction was observed upon reaction of 1 with Ph3P=CH2 (Scheme 8-24) [208],... 

The nature of reagents prepared under different conditions has been explored both structurally and spectroscopically.177 C2H5ZnCH2I, Zn(CH2I)2, and ICH2ZnI are all active methylene transfer reagents. 

Scheme 10.12 gives some examples of enantioselective cyclopropanations. Entry 1 uses the W.s-/-butyloxazoline (BOX) catalyst. The catalytic cyclopropanation in Entry 2 achieves both stereo- and enantioselectivity. The electronic effect of the catalysts (see p. 926) directs the alkoxy-substituted ring trans to the ester substituent (87 13 ratio), and very high enantioselectivity was observed. Entry 3 also used the /-butyl -BOX catalyst. The product was used in an enantioselective synthesis of the alkaloid quebrachamine. Entry 4 is an example of enantioselective methylene transfer using the tartrate-derived dioxaborolane catalyst (see p. 920). Entry 5 used the Rh2[5(X)-MePY]4... 

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. 

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