Directed metalation rearrangement

Direct metallation of o-halogenophenoxyelement derivatives of silicon, tin, and phosphorus leads to an unstable metallated intermediate which undergoes a rapid 1,3-rearrangement under element-carbon bond formation. This type of reaction seems to be a general method for the synthesis of hydroxyphenyl element derivatives [1-4], We have studied the influence of different organoelement groups on the reaction pathway. The yield increases in the sequence R3Sn < R2P < RjSi P(0)(0R)2. 

A simple and flexible synthesis of benzoxathiin-2-one from phenols has been reported. The key step in this synthesis is a hitherto unknown anionic rearrangement under direct metallation conditions <2004T5215, 2003SL1474>. 

Zhang, P. Gawley, R. E. Directed metalation/ Snieckus rearrangement of O-benzylic carbamates./. Org. Chem. 1993, 58, 3223-3224. 

The rearrangement of cubane gives different types of products depending on the metal. With Ag+ ion catalysis, cuneane is produced, whereas with Rh(I), tricyclooctadiene is obtained (Scheme 6.36). Again, these reactions go through direct metal insertion. When, however, the [RhCl(CO)2]2 complex was applied in a stoichiometric amount, the rhodium-inserted cubane complex could be isolated. ... 

Substrate—Aromatic bromides or iodides (Ar-X) are rapidly converted to the corresponding aryllithium (Ar-Li) when treated with 1 molar equivalent of n-BuLi or 2 molar equivalents of (-BuLi. However, some substrates may rearrange to a more thermodynamically stable aryllithium via abstraction of a proton from a more acidic site, and this can lead to the formation of unwanted impurities (Scheme 12.5, eq. 2). Similarly, proton abstraction from aryl bromide substrates that contain an ortfto-directing metalation group (DMG) may lead to impurities in the final product. ... 

A synthesis of annulated 1,4-oxathiin-2-ones involves an anionic rearrangement under directed metalation conditions as the key step. A,A-Diethyl o-methylsulfanylaryl carbamates, readily available from phenols, are deprotonated at the SMe group which initiates rearrangement to a thioacetamide from which the oxathiinone can be obtained (Scheme 31) <0415215>. 

Directed metallation vs. rearrangement of O-arylmethyl carbamates. The selection of the two pathways (site of deprotonation) is dependent on the substitution pattern at the benzylic position. ... 

A new approach to gilvocarcins features directed metallation and a Pd(0)-catalysed Suzuki cross coupling to produce the biaryl precursor. LDA remote metallation precipitates an anionic Fries rearrangement and generates the naphtho[ft,d]benzopyran system <97TL8149>. 

We have tried to summarize in this chapter the basic tendencies and mechanisms of directed metalation. DoM in presence of DMG(s) allows for the regioexhaustive functionalization of aromatics. DreM, frequently combined with migration of the DMG or rearrangement, gives a powerful tool for the synthesis of natural products. Peri and lateral lithiations have shown to further enable functionalization for aromatic scaffolds, and last but not least, when coordinated to and thus activated by a metal complex, aromatic ring systems can be subjected to enantiose-lective metalation reactions. Although such a chapter cannot cover the topic in an exhaustive manner, we hope to have found a compromise between scholarly presentation and citation of relevant literature. 

Representative synthetic methods include Claisen rearrangement, Friedel-Crafts acylation and directed metallation. Bicyclic arylsulfonamides are used to prepare herbicidally active sulfonylureas. Biological activity of these sulfonylureas is discussed. 

From a synthesis-oriented point of view, the rearrangement of 2-(alkenyloxy)-methyllithiums is particularly attractive. Obviously such intermediates cannot be produced by direct metalation of the corresponding ether at the unactivated methyl group. One has to resort instead to a reductive scission of carbon-selenium bonds or to the extremely smooth tin/lithium permutation. The latter approach was exploited in a short synthesis of the Cig Cecropia juvenile hormone starting from the readily available dihydroxyacetal 369 (Scheme 1-287). " As with other a,P-dialkylallyl migrations too, the product is obtained with high (Z/ ) stereoselectivities (>95 5). " ... 

The direct connection of rings A and D at C l cannot be achieved by enamine or sul> fide couplings. This reaction has been carried out in almost quantitative yield by electrocyclic reactions of A/D Secocorrinoid metal complexes and constitutes a magnificent application of the Woodward-Hoffmann rules. First an antarafacial hydrogen shift from C-19 to C-1 is induced by light (sigmatropic 18-electron rearrangement), and second, a conrotatory thermally allowed cyclization of the mesoionic 16 rc-electron intermediate occurs. Only the A -trans-isomer is formed (A. Eschenmoser, 1974 A. Pfaltz, 1977). 

Trichlorosilane. The primary production process for trichlorosilane is the direct reaction of hydrogen chloride gas and sihcon metal in a fluid-bed reactor. Although this process produces both trichlorosilane and sihcon tetrachloride, production of the latter can be minimi2ed by proper control of the reaction temperature (22). A significant amount of trichlorosilane is also produced by thermal rearrangement of sihcon tetrachloride in the presence of hydrogen gas and sihcon. 

Direct treatment of TIPS enol ethers of a variety of cyclic and acyclic ketones with the strong-base combination of n-BuLi/KO-t-Bu leads to /3-ketosilanes (2) after aqueous work-up. In contrast with the earlier method, this rearrangement appears to proceed through allylic, rather than vinylic, metallation, since enol ethers lacking an allylic a-proton are unreactive. 

Directed lithiation of aromatic compounds is a reaction of broad scope and considerable synthetic utility. The metalation of arenesulfonyl systems was first observed by Gilman and Webb and by Truce and Amos who reported that diphenyl sulfone is easily metalated at an orf/io-position by butyllithium. Subsequently, in 1958, Truce and coworkers discovered that metalation of mesityl phenyl sulfone (110) occurred entirely at an orf/io-methyl group and not at a ring carbon, as expected. Furthermore, refluxing an ether solution of the lithiated species resulted in a novel and unusual variation of the Smiles rearrangement and formation of 2-benzyl-4,6-dimethyl-benzenesulfinic acid (111) in almost quatitative yield (equation 78). Several other o-methyl diaryl sulfones have also been shown to rearrange to o-benzylbenzenesulfinic acids when heated in ether solution with... 

Then, contrary to what was reported previously, the olefin dissociates from the zirconium metal complex. This conclusion was further supported by other experimental observations. However, it cannot be completely excluded that competition between dissociative and direct rearrangement pathways could occur with the different isomerization processes studied up to now. Note that with cationic zirconocene complexes [Cp2Zr-alkyl], DFT studies suggest that Zr-alkyl isomerizations occur by the classical reaction route, i.e. 3-H transfer, olefin rotation, and reinsertion into the Zr-H bond the olefin ligand appears to remain coordinated to the Zr metal center [89]. 

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