Subject carbonyl methylenation

The mechanism of carbonyl methylenation with dimethyltitanocene 30 is one of the major subjects of discussion in titanium-carbene chemistry. Two reaction pathways have been proposed. Based on the observation of H/D scrambling in reactions using a deuterated ester and Cp2Ti(CD3)2, Petasis proposed that the reaction proceeds by methyl transfer to form the adduct 31 and subsequent elimination of methane and titanocene oxide (Scheme 4.29, Path A) [64]. Later, a detailed study by Hughes and co-workers using and D-labeled compounds showed that the methylenation of esters with 30 proceeds via a titanium carbene mechanism (Path B) [82]. 

You will note that the oxygen atoms attached to carbons 5 and 12 in 43 reside in proximity to the C-9 ketone carbonyl. Under sufficiently acidic conditions, it is conceivable that removal of the triethylsilyl protecting groups would be attended by a thermodynamically controlled spiroketalization reaction.30 Indeed, after hydro-genolysis of the C-26 benzyl ether in 43, subjection of the organic residue to the action of para-toluenesulfonic acid in a mixture of methylene chloride, ether, and water accomplishes the desired processes outlined above and provides monensin methyl ester. Finally, saponification of the methyl ester with aqueous sodium hydroxide in methanol furnishes the sodium salt of (+)-monensin [(+)-1], Still s elegant synthesis of monensin is now complete.13... 

The C-H bond cleavage of active methylene compounds with a transition metal catalyst is another method for the functionalization of these C-H bonds. To date, several reactions have been developed. In particular, the asymmetric version of this type of catalytic reaction provides a new route to the enantioselective construction of quaternary carbon centers. One of the most attractive research subjects is the catalytic addition of active methylene C-H bonds to acetylenes, allenes, conjugate ene-ynes, and nitrile C-N triple bonds. The mthenium-catalyzed reaction active methylene compounds with carbonyl compounds involving aldehyde, ketones, and a,y3-unsatu-rated ketones and esters is described in this section. 

While we are on the subject of specificity and control in substitution adjacent to a carbonyl, there is another contribution, which I would like to mention because it has turned out to be very important. It is what I refer to as regiospecific enolate formation and trapping. It made possible the introduction of an electrophile, including a carbon chain, on one or the other a-methylenes of a ketone. 

A(, -Dimethyl(methylene)iminium salts have been the most widely used class of preformed iminium salts, mainly due to their applications in the synthesis of a,p-unsaturated carbonyl compounds, normally accomplished by subjecting the /V, -dimethyl Mannich base to quatemarization followed by base-induced elimination. Table 3 outlines various counterion forms of /V, -dimethyl(methylene)iminium salts that have been used in Mannich reactions as well as their synthetic precursors. The crystalline iodide (30), known also as Eschenmoser s salt , has seen the most widespread use and is prepared by thermal fragmentation of (iodomethyl)trimethylammonium iodide or, more conveniently, by a variant of the... 

Leighton constructed the complex molecule of the CP-263,114 core ring system 641 by elegant application of Pd-catalyzed carbonylation of the 1,3-butadienyl 2-triflate moiety in 637 via the methylene-7r-allylpalladium 638 to afford the unsaturated lactone 640. The lactone was subjected to Cope rearrangement to produce 641 as shown by 640 in 56 % overall yield. Formation of the unsaturated lactone 640 by intramolecular acetalization involving the alcohol, ketone, and acylpalla-dium as shown by 639, is a key reaction [228]. 

Photochemical cleavage of metal-carbon bonds constitutes a brief part of a recent review on the photochemistry of metal carbonyls. Reviews of metal-alkyl and -aryl complexes have also appeared, one of which is concerned solely with metals in Groups IV— VII. The other deals with the formation, stability, and decomposition pathways of transition metal-carbon a-bonds, subjects of much interest in recent years. Consequently the recent isolation of the first stable methylene complex [Ta(Me)(CHa)(jj-C6H6)2] and its unequivocal characterization by a single-crystal JlT-ray diffraction study is of great interest in view of the probability that related derivatives are involved in the recently reported (see Vol, 4, p. 293) examples of a-hydride elimination in metal alkyls. 

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