Alkynyl Fischer carbene complexes

The [3+2] cycloaddition of Fischer alkynyl carbene complex 1 with diazomethane was first reported in 1973 (Scheme 5.1) [9]. The reaction initially generates a pyrazole carbene complex 2 as an intermediate, followed by the nucleophilic addition of the second diazomethane to the carbene center, and the denitrogenation occurs to give the A-metalated pyrazole 3. When trimethylsilyldiazo-methane (TMSCHN2) is used instead of diazomethane, the reaction of the initially formed [3+2] cycloadduct with TMSCHN2 was suppressed to give the pyrazole carbene... 

The reactions of Fischer alkynyl carbene complexes 2 with nitrones 21 regioselectivity give dihydroisoxazole carbene complexes 22 in excellent yields (Scheme 5.6) [13]. The electron-withdrawing property of the metal-carbene complexes 20 is confirmed by the density functional theory calculations on the [3+2] cycloaddition [14], The dihydroisoxazole carbene complexes 22 are readily... 

SCHEME 5.2 [3+2] Cycloaddition of Fischer alkynyl carbene complexes 4 with TMSCHN2... 

A. A -Bicychc pyrazolidin-3-ones 31, potentially bioactive heterocycles, are also constructed by the [3+2] cycloaddition of Fischer alkynyl carbene complexes 28 with azomethine imines 29 via isolable metal-carbene intermediates 30 (Scheme 5.8) [17]. 

Heterocyclic 1,3-dipoles 32-34 also react with Fischer alkynyl carbene complexes to give pyrazolyl- and pyrrolyl-carbene complexes (Scheme 5.9) [18]. These reactions proceed along with elimination of carbon dioxide, isocyanate, and sulfur from the initially formed [3-1-2] cycloaddition products. When Fischer alkynyl carbene complexes 35 are treated with 1,3-dipole 33, pyrrolylcarbene complexes 36 are obtained. 

Azides react with Fischer alkynyl carbene complexes via copper-catalyzed or copper-free [3+2] cycloaddition ( click reaction) [19]. The copper-free click reaction... 

SCHEME 5.11 Cyclopentannulation of Fischer alkynyl carbene complexes 42 with cyclic enam-ines 43. 

The single electron transfer (SET) reduction of Fischer alkynyl carbene complexes 95 with potassium graphite (CgK) results in the formation of cyclopentadienes 100 (Scheme 5.20) [31], The radical anion intermediates 96, generated by the SET reduction of Fischer alkynyl carbene complexes 95, undergo tail-to-tail dimerization to form bis-carbene anions 97. The intermediates 97 are protonated with a strong acid to produce the intermediates 98, which convert in situ into chromium cyclopentadienylcarbene 99. After the demetallation of the cyclopentadienylcarbene 99, cyclopentadienes 100 are obtained. 

Fischer-type carbene complexes, generally characterized by the formula (CO)5M=C(X)R (M=Cr, Mo, W X=7r-donor substitutent, R=alkyl, aryl or unsaturated alkenyl and alkynyl), have been known now for about 40 years. They have been widely used in synthetic reactions [37,51-58] and show a very good reactivity especially in cycloaddition reactions [59-64]. As described above, Fischer-type carbene complexes are characterized by a formal metal-carbon double bond to a low-valent transition metal which is usually stabilized by 7r-acceptor substituents such as CO, PPh3 or Cp. The electronic structure of the metal-carbene bond is of great interest because it determines the reactivity of the complex [65-68]. Several theoretical studies have addressed this problem by means of semiempirical [69-73], Hartree-Fock (HF) [74-79] and post-HF [80-83] calculations and lately also by density functional theory (DFT) calculations [67, 84-94]. Often these studies also compared Fischer-type and... 

Electrophilic vinylidene complexes, capable of reacting with non-carbon nucleophiles to yield Fischer-type carbene complexes, can be obtained by addition of electrophiles to alkynyl complexes (Figure 2.11, Table 2.7, Entries 11, 12) [134,144]. 

A kinetic study of the 1,3-dipolar cycloadditions of alkynyl Fischer carbene complexes with nitrones showed tirst-order kinetics for both nitrones and the alkynyl carbene complexes. The 1,3-dipolar cycloaddition of chiral non-racemic Fischer... 

Alkoxy(l-alkynyl)carbene Complexes via the Fischer Route... 

The preparation of alkoxy(l-alkynyl)carbene complexes (e.g., of compounds L M = C(OR1)—C=CR) mostly follows the two-step Fischer procedure,14 involving addition of a 1-lithio alkyne LiC=CR to a metal carbonyl L M(CO) to give a metal acylate L M=C(CTLi+) — C= CR14, which is subsequently alkylated with an oxonium salt [R130]BF4,15 an alkyl triflate R10S02C — CF3,16,22 or an alkyl fluorosulfonate R103SF16a,n ... 

Because metal carbonyls as well as 1-lithio alkynes31 are readily available, a wide variety of (l-alkynyl)carbene complexes can be obtained via the Fischer route in a procedure32 similar to that given for (CO)sCr=C... 

Pauson-Khand cyclization3k 143 of tV-allyl (l-alkynyl)carbene complexes 134 (M = Cr, W R = Ph, Et R1 = H, Me) affords cyclopentenone derivatives 136144 via cobalt complexes 135145 (Scheme 53), as well as chromium complexes.146 Cyclopentenones also have been derived from 7V-diallyl(l-alkynyl)carbene complexes.39 Stable cobalt complexes of type 135 are obtained from O-allyl (l-alkynyl)carbene complexes. Interestingly, the last-named compounds do not form a cyclopentenone on heating instead, they form an enyne by elimination of M(CO)6 in a retro-Fischer reaction. 147... 

Following the Fischer procedure, alkynyl carbyne complexes trans-X(CO)4M=C—CPh 189 have been obtained in 30-60% yields by reaction of (l-alkynyl)carbene complexes la,b (M = Cr, W) with BX3 (X = Cl, Br, I). To date, (l-alkynyl)carbyne compounds have found application as catalysts as well as stochiometric reagents in organic synthesis.205c-206 Among the transformations reported thus far is the formation of a 4-amino-l-metalla-l-yne-3-ene (= enamino carbyne complex) 190 by addition of HNMe2 to compound 189 (Scheme 79).207... 

The reaction of a,(3-unsaturated Fischer carbene complexes 42 with cyclic enamines 43 gives cyclopentannulation products 46 with complete regioselectivity by a formal [3-1-2] cycloaddition (Scheme 5.11) [20]. The formal [3-1-2] cycloaddition is assumed to occur in a stepwise manner via the 1,4-addition of cyclic enamines 43 to the alkynyl carbene complexes 42 (formation of iminium intermediate 44), the intramolecular cyclization to the formed iminium moiety from the carbene carbon (formation of intermediate 45), and the hydrolysis reaction. When (—)-8-phenylmenthyl derivatives of Fischer carbene complexes 42 are reacted with indoles 43, the corresponding indolinones 46 are obtained with >97% ee. 

Tungsten alkynyl Fischer carbene complexes are excellent dienophile partners in the classical Diels-Alder reaction with 1-azadienes (see Sect. 2.9.2.1). On the contrary, the chromium-derived complexes exhibit a different behaviour and they react through a [4S+3C] heterocyclisation reaction to furnish azepine derivatives [116] (Scheme 68). The reaction is initiated by a 1,2-addition of the nitrogen lone pair to the carbene carbon followed by a [l,2]-Cr(CO)5 shift-pro-... 

A combination of a Diels-Alder and a Fisher carbene-cyclopentannulation is described as the last example in this subgroup. Thus, Barluenga and coworkers used a [4+2] cycloaddition of 2-amino-l,3-butadienes 4-115 with a Fischer alkoxy-arylalky-nylcarbene complex 4-116 this is followed by a cyclopenta-annulation reaction with the aromatic ring in 4-116 to give 4-117 (Scheme 4.25) [36]. An extension of this domino process is the reaction of 4-118 with 2equiv. of the alkynyl carbene 4-119 containing an additional C-C-double bond (Table 4.2) [37]. The final product 4-120, which was obtained in high yield, is formed by a second [4+2] cycloaddition of the primarily obtained cyclopenta-annulated intermediate. 

Etherification using a metal vinylidene has also been combined with G-G bond formation through the reaction of an alkynyl tungsten complex with benzaldehyde (Scheme 14). The addition of an internal alcohol to the incipient /3,/Udialkylvinylidene that is generated leads to dehydration and the formation of a Fischer-type alkylidene complex. Further reactions of this carbene with a range of nucleophiles have provided access to various furan derivatives.374,375... 

Alkenyl and alkynyl Fischer carbene complexes reacted with pyrrole imine 108 to give, through a 1,2- and 1,3-metal migration, respectively, indolizine derivatives at a different level of unsaturation (Scheme 29) <1999JA3065>. 

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