Reactions of Carbene Complexes

Nanaomycin A 103 and deoxyfrenolicin 108 are members of a group of naphthoquinone antibiotics based on the isochroman skeleton. The therapeutic potential of these natural products has attracted considerable attention, and different approaches towards their synthesis have been reported [65,66]. The key step in the total synthesis of racemic nanaomycin A 103 is the chemo-and regioselective benzannulation reaction of carbene complex 101 and allylacety-lene 100 to give allyl-substituted naphthoquinone 102 after oxidative workup in 52% yield [65] (Scheme 47). The allyl functionality is crucial for a subsequent intramolecular alkoxycarbonylation to build up the isochroman structure. However, modest yields and the long sequence required to introduce the... 

Synthesis, Properties, and Reactions of Carbene Complexes of Silver 203... 

Two of the most characteristic reactions of carbene complexes are olefin metathesis and olefin cyclopropanation. Olefin metathesis is a reaction in which the C-C double bond of an alkene is cleaved, and one of the resulting alkylidene fragments combines with the metal-bound carbene to form a new alkene. The second alkylidene fragment forms a new carbene eomplex with the metal. Olefin cyclopropanation is a reaction in which a a bond is formed between the metal-bound alkylidene and each of the two carbon atoms of the alkene, to yield a cyclopropane. 

The normal byproducts formed during the transition metal-catalyzed decomposition of diazoalkanes are carbene dimers and azines [496,1023,1329], These products result from the reaction of carbene complexes with the carbene precursor. Their formation can be suppressed by slow addition (e.g. with a syringe motor) of a dilute solution of the diazo compound to the mixture of substrate and catalyst. Carbene dimerization can, however, also be a synthetically useful process. If, e.g., diazoacetone is treated with 0.1% RuClCpIPPhjij at 65 °C in toluene, cw-3-hexene-2,5-dione is obtained in 81% yield with high stereoselectivity [1038]. 

More attention has been paid to tungsten complexes and Raubenheimer and coworkers502 studied the reactions of carbene complexes such as [W(CO)s C(OEt)Ph) with a variety of electrophiles to give coordinated thioaldehydes. Fischer s group has reported many studies on the behavior of pentacarbonyltungsten-coordinated thiobenzaldehyde [(CO)sW S=C(Ph)H ] with vinyl ethers503 (equation 153) and alkynes504. 

The reaction of carbene complexes with alkynes offers useful synthetic methods. The formation of various cyclic compounds by the reaction of alkynes with the alkoxycarbene complex 259 can be summarized by the following scheme, which is simplified for easy understanding, although the explanation is not exactly correct mechanistically. 

Well-established is the formation of hydroquinone and phenol derivatives 273 from alkynes. This reaction is called the Dotz reaction [78,79]. The reaction of carbene complex 271 to give 273 can be expressed by the general scheme 272. 

Reactions of carbene complexes with phosphorous compounds are topics of current research.164-167 (l-Alkynyl)carbene complexes (CO)5M= C(OEt) —C=CR 1 (M = Cr, W R = Ph, r-Bu, SiMe3) readily add tertiary phosphanes PPhR2 (R = Ph, Me) and form stable zwitterionic phosphonium allenide complexes (CO)5M —C(OEt)=C=C(R)—P+PhR2 145, which have been characterized by X-ray diffraction (Scheme 57).55 In previous studies on Michael-type additions of nitrogen and oxygen nucleophiles to (l-alkynyl)carbene complexes 1, zwitterionic allenide complexes of type 145 have been postulated as intermediates.21,23,503 62 112,168,169 Unambiguous structural evidence of the tendency to form such intermediates is given by isolation of a stable zwitterionic adduct, such as compound 145. Zwitterionic... 

Irradiation of Fischer carbene complexes generates, by insertion of carbon monoxide, a metal-bound ketene intermediate. Photolytic reactions of carbene complexes are synthetically attractive, in that the reaction conditions are mild and the reactions of ketene intermediates with a variety of reagents is of significant scope. A low concentration of metal-bound ketene is probably obtained and in the absence of a nucleophile, the starting material can usually be recovered even after prolonged irradiation. The ketene intermediates are readily trapped with nucleophiles for example, dipeptides are formed in excellent yield and with very high diastereoselectivity upon irradiation of optically active carbenes in the presence of natural or urmatural a-amino acids (Scheme 28). Dipeptides and PEG-supported amino acids and dipeptides can also be used as nucleophiles. 

Both of the examples of intramolecular Diels-Alder reactions of carbene complexes involve the 1,3-diene tethered through the heteroatom ancilliary substituent of the carbene carbon. - The example shown in Scheme 11 is the only example of a Diels-Alder reaction of an amino carbene complex. Al-kenylamino and alkynylamino complexes are inert to reaction under intermolecular conditions with very reactive dienophiles, such as cyclopentadiene and Danishefsky s diene. - The aminolysis of the meth-oxy complex (48b) with the amine (75) represents the most common method for the preparation of amino carbene complexes. - It is typical that two isomeric amino carbene complexes are obtained by this procedure, and, as is the case for the complexes (76) and (77), it is also typical that these isomers about the carbene-nitrogen bond are not interconvertable, even at elevated temperatures. The ( )-isomer (76) was separated and was found to undergo an intramolecular Diels-Alder reaction at 80 °C to give the interesting tricyclic caibene complex (78). 

Very few pericyclic reactions of carbene complexes have been studied that are not in the cycloaddition class. The two examples that are known involve ene reactions and Claisen rearrangements. Both of these reactions have been recently studied and thus future developments in this area are anticipated. Ene reactions have been observed in the the reactions of alkynyl carbene complexes and enol ethers, where a competition can exist with [2 + 2] cycloadditions. Ene products are the major components firom the reaction of silyl enol ethers and [2 + 2] cycloadducts are normally the exclusive products with alkyl enol ethers (Section 9.2.2.1). As indicated in equation (7), methyl cyclohexenyl ether gives the [2 -t- 2] adduct (84a) as the major product along with a minor amount of the ene product (83a). The t-butyldimethylsilyl enol ether of cyclohexanone gives the ene product 9 1 over the [2 + 2] cycloadduct. The reason for this effect of silicon is not known at this time but if the reaction is stepwise, this result is one that would be expected on the basis of the silicon-stabilizing effect on the P-oxonium ion. 

One of the first reactions of carbene complexes to be investigated after their discovery was the cyclo-propanation of aikenes. This reaction has been extensively studied and will only be briefly surveyed here. Two excellent reviews of this subject have appeared, - and the cyclopropanation of aikenes with... 

In Fischer s original synthesis, carbyne complexes were obtained fortuitously as products of the reactions of carbene complexes with Lewis acids. For example, the methoxycarbene complex Cr(CO)5[C(OCH3)C6H5] reacts with the Lewis acids BX3 (X = Cl, Br, or I). 

Reaction of Carbene Complex 1 with Alkenes General Procedure ... 

In the Diels-Alder reaction, the typical dienophile will display lower stereoselectivity with acyclic dienes than with cyclic dienes. This is the case for the reactions of both methyl crotonate and the prope-nyl tungsten complex (52b) with Danishefsky s diene (Scheme 9). Carbene complex (52b) gives a 58 42 selectivity in favor of the exo adduct (66), while methyl crotonate gives a similar selectivity of 66 34 in favor of the exo adduct (63) (64 and 65 are both derived from elimination of methanol from the endo adduct). This example reveals that the Diels-Alder reactions of carbene complexes are viable with functionalized and highly electron rich dienes. Furthermore, although the reaction of the carbene complex (52b) with Danishefsky s diene is not stereoselective, it does occur with a much greater rate and efficiency than that for the organic ester for which it can serve as synthon. 

A comprehensive treatment of the benzannulation of Fischer carbene complexes with alkynes is not possible in this review, and thus instead the material presented here will hopefully serve to give the reader an overview of its scope and limitations. The first report of this reaction was in 1975 by Dotz in which he describes the formation of the naphthol chromium tricarbonyl complex (236) from the reaction of the phenyl chromium complex (la) with diphenylacetylene. In the intervening years over 100 papers have been published describing various aspects of this reaction.The reaction of the generic cartene complex (233 Scheme 34) with alkynes will serve to focus the organization of the scope and limitations of the benzaimulation reaction. The issues to be considered are (i) the regioselectivity with unsymmetri-cal alkynes (ii) possible mechanisms (iii) applications in natural product syntheses (iv) the effect of substitution on the aryl or alkenyl substituent of the carbene carbon (v) functionality on the alkyne (vi) effects of the solvent and the concentration of the alkyne (vii) tandem applications with other reactions of carbene complexes (viii) reactions where aromatization is blocked (cyclohexadienone annulation) (ix) annulation of aryl versus alkenyl carbene complexes (x) the effect of the ligands L on the metal (xi) the effect of the ancilliary substituent RX and (xii) reactions with —C X functionality. 

---