Carbene complexes nucleophilic addition reactions

S+3C] Heterocyclisations have been successfully effected starting from 4-amino-l-azadiene derivatives. The cycloaddition of reactive 4-amino-1-aza-1,3-butadienes towards alkenylcarbene complexes goes to completion in THF at a temperature as low as -40 °C to produce substituted 4,5-dihydro-3H-azepines in 52-91% yield [115] (Scheme 66). Monitoring the reaction by NMR allowed various intermediates to be determined and the reaction course outlined in Scheme 66 to be established. This mechanism features the following points in the chemistry of Fischer carbene complexes (i) the reaction is initiated at -78 °C by nucleophilic 1,2-addition and (ii) the key step cyclisation is triggered by a [l,2]-W(CO)5 shift. 

Intramolecularity was the next issue to be probed within the context of alkynyliodonium salt/nucleophile addition reactions.53 1 No prior history was available to guide us, and so the prospects for success remained uncertain. Of primary concern was the potential for iodonium salt/base destructive interactions in competition with the desired N-H deprotonation reaction. A substrate that bore some resemblance to key portions of the agelastatin precursor 33 was prepared (Scheme 6), compound 39. This species duplicated the alkynyliodonium/"amide" pairing of the real system, but it lacked the complex piperazine carbene trap of 33. The tosylimide (pre)nucleophile was proposed as a compromise between what we really wanted (an N-methyl amide) and what would likely work (a tosylamide). Simple treatment of 39 with mild base effected the desired bicyclization to afford the tosylimide product 41 in decent yield. A transition state model 40 for C-H insertion that features an equatorial phenyl unit might rationalize the observed sense of diastereoselectivity. So, at least for 39, no evidence for possible interference by iodonium/base reactions was detected. 

Addition of the acetylenic alcohols HC=C(CH2) OH (x = 3,4) to 1 affords a one-pot synthesis of the cyclic carbene complexes (88). The reaction proceeds via initial formation of the vinylidene complexes, followed by an intramolecular attack of the terminal alcohol function on the a carbon [Eq. (84)] (85). Combining the nucleophilicity at the /3 carbon of... 

This chapter will focus on the nucleophilic addition reactions of transiton metal carbene and carbyne complexes with Grignard reagents. The synthesis and some general reactions of these carbene and carbyne complexes will be presented. A more detailed description of the chemistry of these complexes can be found in the literature [1]. This chapter, although not exhaustive, is descriptive of the prototypical nucleophilic addition reactions of metal-carbon (M-C) multiple bonds with Grignard reagents. 

MO calculations suggest that, in nucleophilic addition reactions of substituted benchrotrenes [( -PhX)Cr(CO)3] (see Vol. 9, ref. 412), the preferred orientation of addition is influenced more by the conformation of the Cr(CO)a residue than by the electronic character of the substituent X. Whereas lithiation (with BuLi-TMED) of 3-methoxybenzyl alcohol occurs very predominantly at the 2-position of the arene ring, similar treatment of the corresponding n-Cr(CO)3 complex gives a mixture of the 2- and 4-lithio derivatives in the ratio 23 77, respectively these products were characterized by isolation of carboxylic acid derivatives following carbonation (COg) and metal decomplexation hv 0. Experimental details for the preparation of [(iy-PhX)Cr(CO)3] (X=I and SiMes) from [( -PhLi)Cr(CO)3] have been reported. This lithio derivative has also been used to prepare the carbene complexes [(OC)3Cr(i7-Ph)C(OEt)M(CO)5] (M=Cr, Mo, and W), which react with BX, (X=C1 and Br) to give the carbyne products [(OC)3Cr( Ph)C=M(CO)4X] (M=Cr and W only). ... 

The ease of formation of the carbene depends on the nucleophilicity of the anion associated with the imidazolium. For example, when Pd(OAc)2 is heated in the presence of [BMIM][Br], the formation of a mixture of Pd imidazolylidene complexes occurs. Palladium complexes have been shown to be active and stable catalysts for Heck and other C-C coupling reactions [34]. The highest activity and stability of palladium is observed in the ionic liquid [BMIM][Brj. Carbene complexes can be formed not only by deprotonation of the imidazolium cation but also by direct oxidative addition to metal(O) (Scheme 5.3-3). These heterocyclic carbene ligands can be functionalized with polar groups in order to increase their affinity for ionic liquids. While their donor properties can be compared to those of donor phosphines, they have the advantage over phosphines of being stable toward oxidation. 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

Photodriven reactions of Fischer carbenes with alcohols produces esters, the expected product from nucleophilic addition to ketenes. Hydroxycarbene complexes, generated in situ by protonation of the corresponding ate complex, produced a-hydroxyesters in modest yield (Table 15) [103]. Ketals,presumably formed by thermal decomposition of the carbenes, were major by-products. The discovery that amides were readily converted to aminocarbene complexes [104] resulted in an efficient approach to a-amino acids by photodriven reaction of these aminocarbenes with alcohols (Table 16) [105,106]. a-Alkylation of the (methyl)(dibenzylamino)carbene complex followed by photolysis produced a range of racemic alanine derivatives (Eq. 26). With chiral oxazolidine carbene complexes optically active amino acid derivatives were available (Eq. 27). Since both enantiomers of the optically active chromium aminocarbene are equally available, both the natural S and unnatural R amino acid derivatives are equally... 

The majority of gold(I) carbene complexes are pure organometallic compounds and the are out of the scope of this work. Some halide or triphenylphosphine carbene complexes are known and they will be considered here. Nucleophilic addition of alcohols or amines to gold-coordinated isocyanides is one of the best-established methods to obtain gold carbene derivatives. The reaction of H[Au(CN)2] with propene oxide and estirene oxide yields (cyano)carbene complexes (380) avoiding the intermediate step.2257 A cyclic carbene compound is obtained by reaction of a dinuclear isocyanide with amine (Scheme 32).2258... 

Self-consistent field molecular orbital calculations by Fenske and coworkers have confirmed that nucleophilic additions to Fischer and related complexes [e.g., (CO)sCr=CXY, (T)5-C5H5)(CO)2Mn=CXY], are frontier orbital-controlled rather than charge-controlled reactions (7-9). Interaction of the HOMO of the nucleophile with the carbene complex LUMO (localized on Ca) destroys the metal-carbon w-interaction and converts the bond to a single one. 

The effect of metal basicity on the mode of reactivity of the metal-carbon bond in carbene complexes toward electrophilic and nucleophilic reagents was emphasized in Section II above. Reactivity studies of alkylidene ligands in d8 and d6 Ru, Os, and Ir complexes reinforce the notion that electrophilic additions to electron-rich compounds and nucleophilic additions to electron-deficient compounds are the expected patterns. Notable exceptions include addition of CO and CNR to the osmium methylene complex 47. These latter reactions can be interpreted in terms of non-innocent participation of the nitrosyl ligand. 

It was noted in Section V,B that the chlorophenyl carbene complex 85 can be prepared by chlorine addition to carbyne complex 80. Treatment of 85 with one equivalent of PhLi does not afford 80, suggesting that the reaction sequence is reduction/substitution rather than substitution/reduc-tion. The recent report (127) of a nucleophilic displacement reaction of the molybdenum chlorocarbyne complex 87 with PhLi to generate phenylcar-byne complex 88 suggests that the intermediacy of the chlorocarbyne complex 86 in the above mechanism is not unreasonable. 

Monomeric carbene complexes with 1 1 stoichiometry have now been isolated from the reaction of 4 (R = Bu, adamantyl or 2,4,6-trimethylphenyl R = H) with lithium l,2,4-tris(trimethylsilyl)cyclo-pentadienide (72). The crystal structure of one such complex (R = Bu) revealed that there is a single cr-interaction between the lithium and the carbene center (Li-C(carbene) 1.90 A) with the cyclopentadienyl ring coordinated in an if-fashion to the lithium center. A novel hyper-valent antimonide complex has also been reported (73). Thus, the nucleophilic addition of 4 (R = Mes R = Cl) to Sb(CF3)3 resulted in the isolation of the 1 1 complex with a pseudo-trigonal bipyramidal geometry at the antimony center. 

Several other observations suggest that nucleophilic carbene complexes, similarly to, e.g., sulfur ylides, can cyclopropanate acceptor-substituted olefins by an addition-elimination mechanism. If, e.g., acceptor-substituted olefins are added to a mixture of a simple alkene and the metathesis catalyst PhWCl3/AlCl3, the metathesis reaction is quenched and small amounts of acceptor-substituted cyclopropanes can be isolated [34]. 

Ylide formation, and hence X-H bond insertion, generally proceeds faster than C-H bond insertion or cyclopropanation [1176], 1,2-C-H insertion can, however, compete efficiently with X-H bond insertion [1177]. One problem occasionally encountered in transition metal-catalyzed X-H bond insertion is the deactivation of the (electrophilic) catalyst L M by the substrate RXH. The formation of the intermediate carbene complex requires nucleophilic addition of a carbene precursor (e.g. a diazocarbonyl compound) to the complex Lj,M. Other nucleophiles present in the reaction mixture can compete efficiently with the carbene precursor, or even lead to stable, catalytically inactive adducts L M-XR. For this reason carbene X-H bond insertion with substrates which might form a stable complex with the catalyst (e.g. amines, imidazole derivatives, thiols) often require larger amounts of catalyst and high reaction temperatures. 

Fullerenes, among which the representative and most abundant is the 4 symmetrical Cgg with 30 double bonds and 60 single bonds, are known to behave as electron-deficient polyenes rather than aromatic compounds [7]. The energy level of the triply degenerate LUMO of Cgg is almost as low as those of p-benzoquinone or tetracyanoethylene. Thus, a wide variety of reactions have been reported for Cgg such as nucleophilic addition, [4-1-2] cycloaddition, 1,3-dipolar addition, radical and carbene additions, metal complexation, and so on [7]. Fullerene Cgg also undergoes supramolecular complexation with various host molecules having electron-donating ability and an adequate cavity size [8]. 

Nucleophilic additions to alkenes 293 Nucleophilic vinylic substitution (SNV) Reactions 298 Nucleophilic substitution of Fischer carbene complexes 303 Reactions involving carbocations 309 Miscellaneous reactions 312... 

Other reactions for which a discussion of their structure-reactivity behavior in terms of the PNS has provided valuable insights include nucleophilic addition and substitution reactions on electrophilic alkenes, vinylic compounds, and Fischer carbene complexes reactions involving carbocations and some radical reactions. 

The fact that the intrinsic rate constants for nucleophilic addition to Fischer carbene complexes are relatively low, for example, much lower than for most reactions with comparable vinylic substrates or carboxylic esters,188 constitutes strong evidence for the presence of substantial transition state imbalances. However, there have only been a few studies of substituent effects that demonstrate the imbalance directly by showing a uc > p uc or by providing an estimate of its magnitude from the difference a uc - p uc. One such study is the reactions of 76-Cr-Z and 76-W-Z with HC CCII20 and C.F3CH20, 183 It yielded a Llc 0.59 and p ]uc< 0.46 for 76-Cr-Z, and a[juc 0.56 and 0 42 for 76-W-Z, i.e., a ue > p uc as expected. 

Reaction of crowded chromium alkenyl Fischer carbene (50) with bulky ketene acetals provides an interesting entry to 3-substituted pent-l-ynoate (53)45 Formation of the alkyne can be rationalized by a 1,4-nucleophilic addition of the ketene on the unsaturated carbene complex (crowded complexes will not undergo potential 1,2-addition), following by oxonium (51) formation and fragmentation to a vinylidene carbene complex (52), which undergoes a 1,3-shift to the alkynylchromium complex leading the alkyne after reductive elimination. 

The stereoselective synthesis of 1,4-disubstituted-l,3-dienes proceeds by head-to-head oxidative coupling of two alkynes with formation of an isolable metallacyclic biscarbene ruthenium complex [23], as shown in Scheme 6. Several key experiments involving labeled reagents and stoichiometric reactions and theoretical studies support the formation of a mixed Fischer-Schrock-type biscarbene complex which undergoes protonation at one carbene carbon atom whereas the other becomes accessible to nucleophilic addition of the carboxylate anion (Scheme 6) [23]. 

We have already established that the carbene carbon is an electrophilic center and, hence, it should be very easily attacked by nucleophiles. In most reactions we believe that the first reaction step probably involves attachment of a nucleophile to the carbene carbon. In some cases, for instance with several phosphines (49) and tertiary amines (50), such addition products are isolable analytically pure under certain conditions (1 in Fig. 3). For the second step there exists the possibility that the nucleophilic agent may substitute a carbon monoxide in the complex with preservation of the carbene ligand (2 in Fig. 3). One can also very formally think of the carbene complex as an ester type of system [X=C(R )OR with X = M(CO)j instead of X = 0], because the oxygen atom as well as the metal atom in the M (CO) 6 residue are each missing 2 electrons for attainment of an inert gas configuration. So, it is not surprising that the... 

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