Metal-dependent chemoselectivity

A polar solvent like DMF is known to accelerate the oxidative addition of a C — I bond by low-valent metals, which is thought to be the preceding step for the formation of 2-iodovinylidene intermediates 77. Scheme 6.27 illustrates one application of this solvent-dependent chemoselectivity, that l-iodo-naphthen-2-ols 79 and 6-iodo-7-oxa-benzocydoheptenes 80 can be selectively produced in DMF and benzene using the same substrate. 

Intramolecular carbon-hydrogen insertion reactions have well known to be elTectively promoted by dirhodium(ll) catalysts [19-23]. Insertion into the y-position to form five-membered ring compounds is virtually exclusive, and in competitive experiments the expected reactivity for electrophilic carbene insertion (3°>2° 1°) is observed [49], as is heteroatom activation [50]. A recent theoretical treatment [51] confirmed the mechanistic proposal (Scheme 15.4) that C-C and C-H bond formation with the carbene carbon proceeds in a concerted fashion as the ligated metal dissociates [52]. Chemoselectivity is dependent on the catalyst ligands [53]. 

Simple Fe3+ salts have rarely been used for catalytic allylic oxidations. Covalent metal nitrates are well known to be strong oxidants which undergo dissociation of the bidentate metal nitrate bond resulting in the formation of the N03 radical as reactive species [105], However, Sahle-Demessie and coworkers were the first who showed the utility of even commercially available Fe(N03)3-9H20 as an oxidation catalyst [106], Turnover and chemoselectivity turned out to be strongly dependent on the alkene substrate and the partial pressure (Scheme 3.20). 

These carbene (or alkylidene) complexes are used as either stoichiometric reagents or catalysts for various transformations which are different from those of free carbenes. Reactions involving the carbene complexes of W, Mo, Cr, Re, Ru, Rh, Pd, Ti and Zr are known. Carbene complexes undergo the following transformations (i) alkene metathesis (ii) alkene cyclopropanation (iii) carbonyl alkenation (iv) insertion to C—H, N—H and O—H bonds (v) ylide formation and (vi) dimerization. Their chemoselectivity depends mainly on the metal species and ligands, as discussed in the following sections. 

Diazocarboxylate esters can be transformed by transition metal catalysts such as rhodium(II) acetate into alkoxycarbonylcarbenes that undergo a wide variety of synthetically useful C-H, C-C, C-X, X-H and X-X insertion reactions (where X = heteroatom) [99]. Chemoselectivity of rhodium carbenoids derived from Rh(II) carboxylates and carboxamides has been found to exhibit striking ligand dependency, for example in work by Padwa showing that perfluorocar-boxamide ligands exclusively promoted aromatic C-H insertions in Rh(II)-cat-alyzed decomposition of diazoamides to give oxindoles, whereas a carboxylate-based rhodium catalyst promoted other types of insertions and addition reactions [100]. 

Oxidation of primary and secondary alcohols by oxoammonium salts derived from nitroxides has become very popular because of the very mild and chemoselective reaction conditions available (Scheme 13). The stoichiometric oxidant can often be an inexpensive reagent, such as hypochlorite (bleach), O2 with a metal catalyst, electrochemical anodic oxidation, peracid, or bromine. The oxoammonium salt can be either pre-formed and used stoichiometrically or generated catalytically from the nitroxide in situ. The mechanism of the reactions is pH dependent strongly acidic conditions chemoselectively oxidize secondary alcohols with accelerated rates over primary alcohols, whereas basic or mildly acidic conditions provide chemoselective oxidation of primary alcohols in the presence of secondary alcohols. A compre-... 

Cyclodimerization of 1,3-butadiene via arene metal-mediation has received relatively little attention. To date, the only example of such a dimerization has been described by Zenneck and co-workers [46]. This group has shown that (r -arene)(r[ -diazadiene)iron complexes catalyze 1,3-butadiene dimerization to afford a mixture of 3-vinylcyclohexene and 1,5-cyclooctadiene. The initial observations showed a strong dependence of [4-1-4]/[4-1-2] product ratio on the nature of the arene coordinated to the metal center. These early results offer good opportunities for the further improving on the chemoselectivity of this cyclization. 

The authors noticed no C-H/C-D isotope effect for the reaction of 13 with methanol and ferf-butanol, but saw a KIE k Jk = 1.4) for the O-H/O-D bond, suggesting that the stronger O-H bond is activated preferentially over the weaker C-H bonds (Pig. 12). In addition, the authors observed the formation of acetone upon the oxidation of tert-butanol. Upon comparison of rate constants (which have been normalized to account for the amount of hydrogens available for abstraction), tert-butanol reacts 50 times faster than cyclohexane. The authors propose a proton-coupled electron transfer event is responsible for the observed selectivity this complex represents a rare case in which O-H bonds may be homolyzed preferentially to C—H bonds. In further study, 13 was shown to oxidize water to the hydroxyl radical by PCET [95]. Under pseudo-first-order conditions, conversion of 13 to its one-electron reduced state was found to have a second-order dependence on the concentration of water, in stark contrast to the first-order dependence observed for aUphatic hydrocarbons and alcohols. Based on the theimoneutral oxidation of water (2.13 V v. NHE in MeCN under neutral conditions [96]) by 13 (2.14 V V. NHE in MeCN under neutral conditions) and the rate dependence, the authors propose a proton-coupled electron transfer event in which water serves as a base. While the mechanism for O-H bond cleavage of alcohols and water is not well understood in these instances, the capacity to cleave a stronger O-H bond in the presence of much weaker C-H bonds is a tremendous advance in metal-oxo chemistry and represents an exciting avenue for chemoselective substrate activation. 

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