Titanacycles

As already indicated, the carbometallation reactions of zirconacyclopropanes and zirconacyclopropenes with alkenes and alkynes are in many ways similar to the corresponding reactions of titanacycles developed more recently. At the same time, however, there are a number of significant differences, as detailed in Section 10.06.2.2. At the present time, synthetically useful carbotitanation reactions are predominantly cyclic and stoichiometric in Ti and more so than the corresponding chemistry of Zr. It seems reasonable to state that Ti and Zr are complementary to each other more often than not. The cyclic carbozirconation may be either stoichiometric or catalytic. Frequently, the difference between the two is that the stoichiometric reactions lack one or more microsteps for completing catalytic cycles. Otherwise, they often share same stoichiometric microsteps. With this general notion in mind, many stoichiometric carbozirconation reactions have indeed been developed into Zr-catalyzed reactions, as discussed later. 

Recently, the conversion of alkenes or non-activated internal alkynes into the corresponding carboxylic acids and/or butenolides has been achieved through carboxylation of titanacycle intermediates of type 73 with carbon dioxide (Scheme 27).78... 

Nucleophilic additions of titanium nucleophiles to nitriles or isonitriles are relatively rare. Eisch et al. recently reported the formation of three-membered ring titanacycles of type 84 and their reactions with benzonitrile and carbon dioxide, respectively (Scheme 34).119,120... 

Similar to the reaction of zirconacyclopropene 1, titanacyclopropene 14 reacted with C02 to give titanacycle 15 (Scheme 5) I0,i0a-i0c j-[owever5 the reaction of Cp TiC /Mg with l,4-bis(trimethylsilyl)-l,3-butadiyne did not afford a titanacyclocumulene species, but yielded titanacyclopropene instead 16, which on reaction with C02 gave the titanacycle complex 17.7 In the case of the titanium half-metallocene complex 18, the five-membered titanacyclocumulene 19 was obtained but the insertion of C02 took place only at one of the two Ti-carbon bonds, leading to the formation of 20 (Scheme 5),11 which is in contrast with what was observed in the case of the Zr analog 3. The... 

The bisfunctionalization of alkynes by both C02 and another electrophile can also be achieved, as shown in Scheme 9.17,17a The titanium-carbon bond in the titanacycle complex 31, which was formed by reaction of C02 with the titanacyclopropene 30, can be substituted with various electrophiles. For example, its reaction with NBS or I2 afforded the synthetically useful vinyl bromide or iodide 32, respectively, while the reaction with D20 yielded the /3-deuterated a,/ -unsaturated carboxylic acid. When an aldehyde such as PhCHO was used as an electrophile, butenolide 33 was produced after acidic workup. 

A titan acycl open tadi en e generated from an acetylene having an ester group at a suitable position reacts intramolecularly with this functional group, as exemplified by Eq. 9.13. Here, both carbon—titanium bonds of the titanacycle participate in the reaction to effect ring-closure [33]. 

As well as undergoing carbonyl addition, titanacyclopentadiene intermediates generated from two unsymmetrical acetylenes have been shown to react with ethynyl para-tolyl sul-fone to afford an aryltitanium compound of the structure shown in Scheme 9.6 [34], The reaction may proceed according to path a or path b, as shown in Scheme 9.7. In path a, the first step should be regioselective [4+2] cycloaddition of the titanacyclopentadiene with the sulfonylacetylene to afford the bicyclic titanacycle, at least in an equilibrium concen-... 

Titanium—acetylene complexes react with allylic or propargylic halides or acetates through regioselective titanacycle formation and subsequent P-elimination [36,37]. The ... 

The cyclization of dienynes was found to proceed equally well, as shown in Eq. 9.55, and the resulting intermediate titanacycle reacts regiospecifkally with aldehydes at the remote position of the most likely allyltitanium system [101]. 

The intramolecular cyclization of l,2-dien-7-ynes and l,2-dien-6-ynes regiospecifically affords the corresponding titanacycles, which react with protons, carbon monoxide, aldehydes, or imines to give single products, as shown in Eqs. 9.56 and 9.57 [102], As the formation of titanacycles and their subsequent reaction with externally added reagents such as carbon monoxide (Eq. 9.56) or an aldehyde (or imine) (Eq. 9.57) proceeds with excellent chirality transfer, this represents a new method for synthesizing optically active cyclopentane derivatives from optically active allenes [102]. 

If the alkenes and acetylenes that are subjected to the reaction mediated by 1 have a leaving group at an appropriate position, as already described in Eq. 9.16, the resulting titanacycles undergo an elimination (path A) as shown in Eq. 9.58 [36], As the resulting vinyltitaniums can be trapped by electrophiles such as aldehydes, this reaction can be viewed as an alternative to stoichiometric metallo-ene reactions via allylic lithium, magnesium, or zinc complexes (path B). Preparations of optically active N-heterocycles [103], which enabled the synthesis of (—)-a-kainic acid (Eq. 9.59) [104,105], of cross-conjugated trienes useful for the diene-transmissive Diels—Alder reaction [106], and of exocyclic bis(allene)s and cyclobutene derivatives [107] have all been reported based on this method. 

Despite the successful reactions mentioned above, olefin metathesis utilizing titanocene-methylidene is not necessarily regarded as a useful synthetic tool. Indeed, the steric interaction between the substituent at the carbon a to titanium and the bulky cyclopentadienyl ligand disfavors the formation of the titanocene-alkylidene 15. Hence, cleavage of the titanacycle affords only titanocene-methylidene and the starting olefin (Scheme 14.9). 

On the contrary, if a highly strained cyclic olefm such as the cyclopropene 16 [20] or the norbornene derivative 17 [21] is employed, the titanacycle is cleaved to form the corresponding titanocene-alkylidene 18 or 19. This reaction is clearly enhanced by the concomitant release of intrinsic strain energy (Scheme 14.10). 

The major obstacle to this approach is that there are few reagents capable of generating higher homologues of titanocene-methylidene. Although the procedure is not straightforward, the titanacycle 21 formed by the addition of diisobutylaluminum hydride to the double bond of (l-propenyl)titanocene chloride 22 serves as a titanocene-propylidene 23 equivalent in carbonyl olefmation (Scheme 14.12) [22]. 

The alkyl-substituted titanium carbene complex 18 reacts with norbornene 24 to form a new titanacycle 25, which can be employed for the ROMP of 24 (Scheme 14.13). The titanacycle generated by the reaction of the Tebbe reagent with 24 is also used as an initiator for the same polymerization [23]. These preformed titanacyclobutanes also initiate ROMP of various other strained olefin monomers [24],... 

Titanacyclobutanes also serve as useful synthetic intermediates the titanacycle 43, prepared by the intramolecular reaction of the alkenylidene complex 44, affords the a-dike-tone 45 and the other functionalized cyclic compounds by further transformations (Scheme 14.20) [35]. 

In marked contrast to the above results, double nitrile insertion into both the titanium-alkyl and titanium—vinyl bonds occurs to form the diazatitanacycles 74. Treatment of these titanacycles with dry hydrogen chloride affords the tetrasubstituted pyridine derivatives 75 (Scheme 14.32) [74], On the other hand, 2,3-diphenyltitanacyclobutene reacts with various nitriles to afford the products of mono-insertion, which afford the corresponding unsaturated ketones upon hydrolysis [73,74]. 

Titanocene-catalyzed cycloisomerization of dienynes 181 provided terminal allenes 182 in moderate yields (Scheme 3.91) [128]. The reaction proceeded via the titanacycle 183 and the allene 184 was formed via loss of a /3-hydrogen atom from the allyltitanium species. 

A bis-silylated l,2-octadien-7-yne undergoes very clean cyclization with a slight excess of (7/2-propene)Ti(OiPr)2, prepared in situ from Ti(OiPr)4 and iPrMgCl, at -50 °C for 2 h to give a 1,4-diene as a single isomer after hydrolytic workup (Scheme 16.71) [78]- Deuteration of the reaction mixture afforded exclusively the bis-deuter-ated product, confirming the presence of an intermediate titanacycle. This reaction seems to be general for other allenes with diverse substitution patterns. 

Ti-mediated cyclization of a l,2-dien-6-yne generates a new allylic titanacycle, which reacts with an aldehyde to give a homoallylic alcohol with high diastereoselec-tivity (Scheme 16.72) [78]. 

Ti-mediated cyclization of an allenynes having a leaving group provides a five-membered ring with cross-conjugated trienes which might be produced by the elimination of an alkoxy group from a titanacycle (Scheme 16.73) [79]. 

Titanium-catalyzed cyclization/hydrosilylation of 6-hepten-2-one was proposed to occur via / -migratory insertion of the G=G bond into the titanium-carbon bond of the 77 -ketone olefin complex c/iatr-lj to form titanacycle cis-ll] (Scheme 16). cr-Bond metathesis of the Ti-O bond of cis- iij with the Si-H bond of the silane followed by G-H reductive elimination would release the silylated cyclopentanol and regenerate the Ti(0) catalyst. Under stoichiometric conditions, each of the steps that converts the enone to the titanacycle is reversible, leading to selective formation of the more stable m-fused metallacycle." For this reason, the diastereoselective cyclization of 6-hepten-2-one under catalytic conditions was proposed to occur via non-selective, reversible formation of 77 -ketotitanium olefin complexes chair-1) and boat-1), followed by preferential cyclization of chair-1) to form cis-11) (Scheme 16). 

E. J. Corey recently described (Organic Lett. 2005, 7,2699, 2703) an even more elegant approach to the y-lactam. Exposure of 5 to the Kulinkovich conditions followed by iodination delivered 18, presumably by way of the titanacycle 17. Although all-carbon trans-5,5 systems are strained, the trans ring fusion is the expected stereochemical outcome with (RO),Ti in the ring. Complexation of the ester to the Ti may explain the observed facial selectivity. Brief exposure of 18 to Et,N followed by silylation converted it to 6. The preparation of several more analogues in this series is also reported in these two articles. 

The stability of the metallocene complexes is strongly dependent on the nature of the cyclopropene substituents, and the reaction conditions. Thus, when equimolar amounts of 3,3-dimethylcyclopropene and Cp2Ti(PMe3)2 react at 0 °C, a 2 1 mixture of alkylidene and cyclopropene complexes is formed. However, when excess of cyclopropene is used, a dicyclopropyl titanacycle is exclusively formed by oxidative coupling reaction of the intermediate cyclopropene complex (equation 215)77. The analogous zirconium oxidative-coupling product is obtained upon reaction of 3,3-dimethylcyclopropene with Cp2(PMe3)Zr( j2-CH2=CHEt) (Section IV.B.2). 

The titanacycle 32a exhibits a half-chair conformation as depicted in Figure 5. The Ti—S bond lengths (2.430 A and 2.437 A) are within the normal range (2.42-2.45... 

This methodology was extended by Dubac and coworkers81 and Meier-Brocks and Weiss82. Titanacycles, zirconacycles and hafnacycles were treated with various halogenogermanes (equation 26). 

Hartree-Fock methods overview, 1, 645 lanthanide hydrocarbonyls, 4, 4 polyhedral carboranes, 3, 50 silicon-bridged ansa-titanocenes, 4, 624 titanacycles, 4, 568 zinc species, 2, 316... 

Reductive Cyclization of 1,6- and 1,7-Dienes, Diynes, Enynes and Arenes via Zirconacycles and Titanacycles... 

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