Carbene synthetic utility

Photolytically generated carbene, as mentioned above, undergoes a variety of undiscriminated addition and insertion reactions and is therefore of limited synthetic utility. The discovery (3) of the generation of carbenes by the zinc-copper couple, however, makes carbene addition to double bonds synthetically useful. The iodo-methylzinc iodide complex is believed to function by electrophilic addition to the double bond in a three-center transition state giving essentially cis addition. Use of the... 

The synthetic utility of the ring expansion reaction was demonstrated by its application to the synthesis of thermolabile thiepins. When the diazo compound (66) obtained from benzo[c]thiopyrylium salt 65 was treated with palladium catalyst under the same conditions as in the case of 63, the product isolated was ethyl 2-naphthoate (68)48). The plausible reaction pathway is one comprising i) decomposition of 66 to the corresponding carbene intermediate, ii) ring expansion to the... 

The potential synthetic utility of titanium-based olefin metathesis and related reactions is evident from the extensive documentation outlined above. Titanium carbene complexes react with organic molecules possessing a carbon—carbon or carbon—oxygen double bond to produce, as metathesis products, a variety of acyclic and cyclic unsaturated compounds. Furthermore, the four-membered titanacydes formed by the reactions of the carbene complexes with alkynes or nitriles serve as useful reagents for the preparation of functionalized compounds. Since various types of titanium carbene complexes and their equivalents are now readily available, these reactions constitute convenient tools available to synthetic chemists. 

Carbenoid reactions are, of course, of considerable synthetic utility in organic chemistry, but consideration of this aspect is beyond the scope of the present work. While reactions in solution will be the major preoccupation, evidence from investigations of carbenes in the gas phase and in the solid state will also be included, although due caution must be exercised in translating conclusions from one phase to another. 

The ruthenium carbene complex (Grubbs catalyst) which has shown high efficiency in alkene methathesis and related processes, since it displays tolerance toward a wide variety of common functional groups, has also appeared of synthetic utility in the hydrosilylation of ketones to yield silyl ethers-one of the most widely used classes of protecting groups in synthetic chemistry (Eq. 97) [ 151 ]. The reaction requires temperatures above 50 °C, which generate a slightly increased amount of silylated by-products. 

Complexes of type [LyM (CH2)IIX ], where n > 1, have been shown to be useful precursors for hetero- and homobimetallic n(a.,a>) alkanediyl complexes, [LjcM(CH2)bM L, ] (where ML, is not necessarily the same as M Lj,). Such hydrocarbon-bridged binuclear compounds have been proposed as models for intermediates in the Fischer-Tropsch reaction (18,19) and other significant catalytic processes (20-23). Some [LyM (CH2)BX ] complexes are precursors to cyclic carbene complexes (Section III), whereas others have been shown to have synthetic utility in organic chemistry (24). 

Dotz and coworkers prepared several interesting and novel glycosylidene carbenes (259-261) by reaction of lithiated glycal 258 with the appropriate metal carbonyl derivative. The synthetic utility of the formed carbenes was demonstrated by reaction with 3-hexyne to give a mixture of complexed and uncomplexed adducts 262 and 263, respectively. The anomeric chromium carhene 264 was converted to 265 hy exposure to ethoxy ethyne (Scheme 48) [70]. The same workers have carried out a similar chromium-mediated henzannulation (266 —> 268), this time with the chromium on the aromatic fragment [71]. Other sugar-hased carhenes have also been prepared [72]. 

Carbenes are very reactive since they contain divalent carbon, they have the capacity to react to form two new bonds. Two important ways in which this happens are by addition to both ends of a double bond synchronously to give a cyclopropane ring (reaction 4.36) or by insertion into a single bond (reaction 4.37). The former reaction has synthetic utility, since few reactions exist to produce cyclopropane rings in good yields. 

Carbene and radical pathways in pyrolysis of benzisoxazolones 00JHC631. Preparation and synthetic utility of 3-isoxazolols 01OPP515. 

Intramolecular insertion reactions are much more selective because the relative proximity of the various C-H bonds to the carbene center plays a major role in determining product distribution. For this reason, the reaction has synthetic utility and is especially valuable for generating derivatives of highly strained ring systems. Cyclopropanes formed by intramolecular insertion reactions are often major products from alkyl carbenes. A competing process for aliphatic carbenes is stabilization... 

When 1,4-dienes are utilized, the activity of allylic C—H bonds to undergo carbene insertion reactions is further enhanced. For instance, a range of chiral Rh complexes is able to convert 1,4-cyclohexadiene into the corresponding C—H bond insertion product in a high yield and ee in the presence of methyl phenyldiazoacetate la (Scheme 1.6, eqn (1)). The synthetic utility of this methodology was further demonstrated by total synthesis of natural products (+)-indatraline (Scheme 1.6, eqn (2)) and (+)-cetiedil (Scheme 1.6, eqn (3)). ... 

Under suitable conditions, carbene and carb5me ligands can take up protons to generate allcyl derivatives. The proton source must be of low acidity to avoid forther protonolysis of the alkyl product. This methodology is of rather limited synthetic utility. Two examples are shown in Scheme The formation of 65 involves loss of the pyridine li-... 

Schrock-type carbene complexes of transition metals other than titanium are also utilized for carbonyl olefination, although their synthetic utility has not yet been fully investigated. In some cases, their reactions differ from those of titanium-carbene complexes in terms of stereo- and chemoselectivity and are complementary to olefination with titanium reagents. This section describes the use of carbene complexes of various transition metals in carbonyl olefination. 

Transition-metal carbene complexes have proven especially useful in the construction of six-membered rings, primarily in the synthesis of naphthalenes and higher aromatic ring systems. The major method employed is the Dbtz benzannulation reaction (depicted in Scheme 17.12), where an a,p-unsaturated or aryl carbene complex of chromium (78) couples with an alkyne to afford a phenol derivative (76). This reaction has been demonstrated for a vast array of molecular architectures and functionalities and has proven to be a very reliable and efificient process. Perhaps the major limitation on the synthetic utility is the construction of the carbene complex for systems that require structural complexity in the carbene complex. In addition to the Dotz reaction itself, several efforts to develop alternative procedures have been inspired by a detailed understanding of the mechanism of the Dotz reaction. 

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