Allyltitanium preparation

A large number of publications appeared on these aspects5, but most of these studies did not address stereochemical questions. In most cases, a given synthetic problem can be better solved by other allylmetals. Grignard reagents have some importance as intermediates for the preparation of allylboronates (Section D.1.3.3.3.3.2.1.), allylsilanes (Section D.1.3.3.3.5.2.L), allyl-stannanes (Section D. 1.3.3.3.6.2.1.1.), or allyltitanium derivatives (Section D.I.3.3.3.8.2.). 

In general, there are three main types of allyltitanium reagent, usually prepared in situ from allyllithium or allylmagnesium derivatives ... 

The combination of metal tuning and double stereodifferentiation helps to prepare chelation and nonchelation products in the imine series7. In the case of an alkoxy substituent adjacent to the aldimino, the chelation product 10 is predominantly obtained with allylmagnesium chloride, chloromagnesium allyltriethylaluminate or allylzinc bromide, while the use of allyl-boronates or allyltitanium triisopropoxide, which lack the requisite Lewis acidity for chelation, gives 11 with good Cram selectivity. 

Gais and co-workers recently reported the preparation and use of chiral sulfoximine-substituted allyltitanium(iv) complexes of type 78 for the asymmetric synthesis of 3-substituted unsaturated proline derivatives 79 (Scheme 31).108... 

Preparation of allyltitaniums of the type (allyl)Ti(OiPr) 3 from the corresponding allyl-lithium or -magnesium compounds and ClTi(OiPr)3 by transmetallation and their subsequent synthetic utilization have attracted considerable interest because of the advantageous reactivity of the allyltitaniums as compared to other allylmetal complexes in terms of chemo-, regio-, and diastereoselectivity [3], The preparation of certain allyllithium or -magnesium reagents, however, is not necessarily easy, which would seem to limit the utility of this method. 

The following synthetically attractive features of the reaction are apparent. The reaction allows the preparation of allyltitaniums bearing functional groups, thus providing easy access to functionalized compounds (Eq. 9.22). 

Alkylidenecydopropane derivatives can readily be prepared by the reaction of 1 with vinylcyclopropyl carbonates and subsequent trapping of the resulting allyltitaniums with aldehydes or ketones (Eq. 9.24) [44], It should be noted that, in this case, the carbon—carbon bond formation occurs at the less substituted allylic terminus, and not at the more substituted end of the titanium reagent, the latter being the position at which addition to substituted allyltitanium reagents is usually observed. 

The preparation of chiral allyltitanium reagents having a stereogenic center and their utilization in asymmetric synthesis have been pursued. As shown in Eq. 9.27, chiral allyl-... 

In contrast to the allyltitaniums derived from acrolein cyclic acetals, such as 1,2-dicyclo-hexylethylene acetal shown in Scheme 9.8, those derived from acrolein acyclic acetals react with ketones and imines exclusively at the y-position. As shown in Eq. 9.29, the reaction with chiral imines having an optically active 1-phenylethylamine moiety proceeds with high diastereoselectivity, thus providing a new method for preparing optically active 1-vinyl-2-amino alcohol derivatives with syn stereochemistry [53], The intermediate allyltita-nium species has also found use as a starting material for a carbozincation reaction [54],... 

A series of q3-allyltitanium compounds has been prepared, and their jr-structures have been confirmed by spectroscopic methods and X-ray analysis [9]. In these complexes, the alkyl substituents at C-l and C-3 preferably occupy the syn position with respect to the H (or R) at C-2 due to steric reasons. The proposed mechanism for their formation is outlined in Scheme 13.4 [8]. 

These c-complexes have been less extensively studied than the r 3-allyltitanium derivatives. r 1 -Allyltitanocenes can readily be prepared from the corresponding magnesium compounds by reaction with Cp2TiCl2 or by reaction of preformed r 3-allyltitanium complexes with but-2-enyl halides [36]. Crotyl-type reagents, which are accessible only in the E-iso-meric form, add to aldehydes with an anti selectivity (Scheme 13.17). 

The reaction proceeds through ligand exchange and a subsequent P-elimination akin to the oxidative addition of Cp2Zr to allylic ethers [58], In this way, allyltitanium compounds can be obtained from readily available allylic alcohol derivatives and inexpensive Ti(OiPr)4. The method allows the preparation of functionalized allyltitaniums bearing functional groups such as ester or halide (Scheme 13.28). 

The last decade has seen significant progress in the field of allyltitanium chemistry. A broad range of allyltitanium compounds, including functionalized derivatives, is now available. They can be prepared through several synthetic methods from structurally... 

Typical procedure for the preparation of allyltitanium derivatives from allyl halides via oxidative addition, and in situ reaction with aldehydes [57,59]... 

Reductive lithiation of allyl phenyl sulfides.1 This reagent is particularly useful for preparation of allyllithium reagents at temperatures at which the anions are stable. Moreover, regioselectivity in reactions can be achieved by conversion to allyltitanium(IV) complexes by metal exchange with Ti(0-/-Pr)4. Thus the un-symmetrical anion formed from the allyl sulfide 1 with LDMAN reacts with cro-tonaldehyde to give a mixture of 1,2- and 1,4-adducts. The 1,2-adduct 2 can be obtained in high yield as two diastereomers (9 1) by use of the allyltitanium complex (equation I). 

Allyltitanium ate complexes.8 In contrast to organotitanium compounds, which are aldehyde selective, the chemoselectivity of allyltitanium ate complexes depends on the ligands attached to titanium. The most aldehyde-selective allyltitanium ate complex prepared to date is CH2=CHCH2Ti[OCH(CH3) >].jMgCl (1) which reacts... 

The nucleophilic 7i-allyltitanium complex 67 is prepared by the reaction of the conjugated diene 65 with titanocene hydride 66, generated in situ by the treatment of titanocene dichloride with 2 moles of z-PrMgCl [21]. The complex is nucleophilic and reacts with aldehydes regio- and stereoselectively to give homoallylic alcohols [22]. 

The / ,y-unsaturated ester 68 was prepared by the reaction of the 7r-allyltitanium complex 67 with methyl chloroformate [23],... 

The unique phenomena observed for allyltitanium ate complexes appear to be restricted to allyl groups. Reversal of chemoselectivity in methylation reactions has not been observed to date. Ate complexes of the type 122 and 123 react much faster with aldehydes than with ketones 90>, but the reactions are not as clean as with the allyl derivatives. Aromatic nitro and cyano groups are tolerated. In certain situations reversal of diastereoselectivity is possible using 123 (Sect. D.II). Ate complexes prepared from poly-titanates17) are also aldehyde selective.77 ... 

Allyltitanium complexes (22) readily add to carbonyl compounds with high regio- and stereo-selection. They are prepared by reaction of a chlorotitanium complex (21) with an allyl-magnesium or -lithium derivative (equation 13). Some of these unsaturated Ti complexes, like (23)-(25) in Scheme 2, obtained from allylmagnesium halides or allyllithium by reaction with titanium tetraisopropoxide or titanium tetramides, are known as titanium ate complexes . The structure of these ate complexes, at least from a formal point of view, can be written with a pentacoordinate Ti atom. Some ate complexes have synthetic interest, as is the case of (allyl)Ti(OPr )4MgBr which shows sharply enhanced selectivity towards aldehydes in comparison with the simple (allyl)Ti(OPr )3. ... 

The lithiation of ethyl allyl sulfide followed by transmetallation with titanium isopropoxide engenders an allyltitanium reagent formulated as (26 Scheme 8). This and related reagents add to aldehydes or ketones to afford hydroxy sulfides, which are converted to epoxides as shown. The power of this method for the stereoselective generation of even trisubstituted epoxides is evident from Scheme 8 and equation (18). Reagent (26a), prepared as shown in Scheme 8a, undergoes addition to ketone (26b) to afford product exclusively resulting from chelation-controlled diastereofacial addition (as a mixture of epimers at the position shown). ... 

The preparation of allyltitanium compounds including those having functional groups is described by reaction of allylic halides or allylic alcohol derivatives with the system Ti(OPr1)4/MgXPr1 (X = C1, Br) (Scheme 7).24 Analogous allyltitanium complexes have also been reported by treatment of Ti(n) species with allylic alcohol derivatives, which proceeds via an oxidative addition pathway. Their reactions have been studied.25-27 These compounds are used to promote efficient syntheses of alkylidenecyclopropane and cycloalkane derivatives by regioselective reactions with carbonyl compounds,28,29 the stereoselective syntheses of optically active substituted piperidines and pyrrolidines... 

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