1 - -1-alkene chromium carbene

The substituent effects on the alkene were investigated in the reaction of enyne 12 and chromium carbene complex 2c [8]. In the reaction of enyne -12a having a phenyl group on the alkene with Fischer chromium carbene complex 2c, metathesis product 13a was obtained as a main product along with cyclopropane 14 and cyclobutanone 15 (Eq.4). The reaction of Z-12a with 2c gave only... 

If the substituents on generated carbene complex 20 are the same as those on the alkene, this reaction must proceed by a catalytic amount of chromium carbene complex 2 (Scheme 5) [9]. 

Initial reports of cross-metathesis reactions using well-defined catalysts were limited to simple isolated examples the metathesis of ethyl or methyl oleate with dec-5-ene catalysed by tungsten alkylidenes [13,14] and the cross-metathesis of unsaturated ethers catalysed by a chromium carbene complex [15]. With the discovery of the well-defined molybdenum and ruthenium alkylidene catalysts 3 and 4,by Schrock [16] and Grubbs [17],respectively, the development of alkene metathesis as a tool for organic synthesis began in earnest. 

Extensive studies on diastereoselectivity in the reactions of 1,3-dipoles such as nitrile oxides and nitrones have been carried out over the last 10 years. In contrast, very little work was done on the reactions of nitrile imines with chiral alkenes until the end of the 1990s and very few enantiomerically pure nitrile imines were generated. The greatest degree of selectivity so far has been achieved in cycloadditions to the Fischer chromium carbene complexes (201) to give, initially, the pyrazohne complexes 202 and 203 (111,112). These products proved to be rather unstable and were oxidized in situ with pyridine N-oxide to give predominantly the (4R,5S) product 204 in moderate yield (35-73%). 

Another more versatile method involves the photocycloaddition of chromium carbene complexes to alkenes. These transformations can be formally regarded as [2 + 1 + 1] cycloadditions since these carbene complexes are derived from [1 + 1] carbanion insertion reactions to hexacarbonylchromium. 

The use of alkenes with chiral auxiliary groups leads to chiral cyclobutanones 4. Reaction yields of 50 67% and diastereomeric excesses of 86-97% were obtained for the 3-amidocy-clobutanones which were obtained from cycloaddition of the chromium carbene complexes with chiral ene carbamates (see also Section 1.3.4.3.3.).11... 

The advantage of using the photocycloaddition of pentacarbonylcarbenechromium complexes over the ketene cycloaddition method is the absence of ketene dimerization and the avoidance of use of excess alkene in the former method. Also, the mild reaction conditions associated with the use of chromium carbene complexes avoids epimerization and thermodynamic equilibration of 2-monosubstituted cyclobutanones. 

Substituted bicyclo[ . 1.0]alkanes may also be obtained by condensation of secondary amines with 2-haloketones. A variety of nucleophilic reactions can be carried out on the intermediate cyclopropaniminium salt 116251 (Scheme 108). Competing alkene scission and cyclopropanation occurs on reaction of enamines with pentacarbonyl-chromium carbene complexes252 (Scheme 109). N-Silylated allylamines and their derived N-silylated enamines undergo rhodium or copper catalysed cyclopropanation by methyl diazoacetate253 (Scheme 110). 

Whereas Fischer-type chromium carbenes react with alkenes, dienes, and alkynes to afford cyclopropanes, vinylcyclopropanes, and aromatic compounds, the iron Fischer-type carbene (47, e.g. R = Ph) reacts with alkenes and dienes to afford primarily coupled products (58) and (59) (Scheme 21). The mechanism proposed involves a [2 -F 2] cycloaddition of the alkene the carbene to form a metallacyclobutane see Metallacycle) (60). This intermediate undergoes jS-hydride elimination followed by reductive elimination to generate the coupled products. Carbenes (47) also react with alkynes under CO pressure (ca. 3.7 atm) to afford 6-ethoxy-o -pyrone complexes (61). The unstable metallacyclobutene (62) is produced by the reaction of (47) with 2-butyne in the absence of CO. Complex (62) decomposes to the pyrone complex (61). It has been suggested that the intermediate (62) is transformed into the vinylketene complex... 

Several heteroatom nucleophiles, for example, amines, alcohols, thiols, carboxylates, and dialkylphosphines, undergo Michael addition reactions with alkene- and alkyne-substituted carbene complexes. Reaction of alkyne-substituted chromium carbenes with urea affords products derived from Michael... 

A chromium carbene generated in situ firom C1CI2 and a dihaloalkyl daivative, has been utilized to form a variety of ( )-disubstituted alkene compounds (480). The general reaction is summarized in equation (110). Alkenyl halides, sulfides and silanes, as well as dialkyl-substituted alkenes, have been synthesized by this method. 

Narasaka and Sakurai found that chromium carbene complexes, when exposed to a copper(II) reagent, generate acyl radicals by a one-electron oxidation, and these then undergo addition to electron-deficient alkenes (Scheme 4-27) [50J. The resulting copper(I) species reduces the resulting radical to an anion, and subsequent protonation leads to the addition product. This redox type acyl radical transfer reaction works particularly well for aromatic acyl radical systems, for which decarbonylation is not a problem. Related work has also recently appeared [51]. 

Of the transition metals listed above, chromium complexes are the most frequently used. Mechanistic investigations reveal that the transfer of a ligand within a carbene - alkene - metal complex rather than a free carbene is involved in these reactions. The best yields result if equimolar amounts of the alkene and the metal complex are used, the application of a large excess of alkene (ca. 10 mol) is not necessary. 

Transition-metal-aminocarbene complexes do not transfer their carbene ligand to alkenes in an intermolecular fashion. In contrast, the thermal reaction of a chromium-carbene complex, which provides bicyclic compound 5 in good yield, demonstrates the feasibility of the intramolecular process5. 

The synthesis of cyclobutanones can in some cases be accomplished more efficiently by addition of a ketene-iminium salt or a chromium carbene to an alkene. For example, under photochemical conditions, the chromium carbene 174 gave the cyclobutanone 175 as a single diastereomer (3.118). The product 175 was converted to the antifungal antibiotic (-l-)-cerulenin by way of the lactone 176. 

Although the Simmons-Smith reaction has found considerable use in organic synthesis, it is not readily applicable to the formation of highly substituted cyclopropanes, since 1,1 -diiodoalkanes (other than diiodomethane) are not readily available. Substituted zinc carbenoids can be prepared from aryl or a,p-unsaturated aldehydes (or ketones) with zinc metal, and these species can be trapped with an alkene to give substituted cyclopropanes.The addition of chromium carbenes (see Section 1.2.2) to alkenes can be used to effect cyclopropanation to give substituted cyclopropanes. Thus, addition of excess 1-hexene to the chromium carbene 113 gave the cyclopropane 114 as a mixture of diastereomers, with the isomer 114 predominating (4.92). ... 

By photolysis of achiral heteroatom-stabilized chromium carbene complexes chromium-ketene species are generated that undergo [2+2] cycloaddition with chiral alkenes diastereoselectively. ... 

---