Aldol-type reactions Titanium chloride

Chromium carbene complexes, 82 Methyl acrylate, 183 (2R,4R)-Pentanediol, 237 Titanium(IV) chloride, 304 Nitroaldols Nitromethane, 199 Intramolecular reactions Methyl acrylate, 183 Other aldol-type reactions Bis(2-pyridinethiolato)tin(II), 40 Alkoxycarbonylation (see Carboalkoxy-lation)... 

The titanium(IV) chloride-promoted reactions of enol silyl ethers with aldehydes, ketones, and acetals, known as Mukaiyama reaction, are useful as aldol type reactions which proceed under acidic conditions (eq (23)) [20], Enol silyl ethers also undergo the Michael type reactions with enones or p.y-unsaturated acetals (eq (24)) [21]. Under similar reaction conditions, enol silyl ethers are alkylated with reactive alkyl halides such as tertiary halides or chloromethyl sulfides (eq (25)) [22], and acylated with acid halides to give 1,3-diketones (eq (26)) [23]. 

The Mukaiyama reaction is an aldol-type reaction between a silyl enol ether and an aldehyde in the presence of a stoichiometric amount of titanium chloride. The reaction, which displays a negative volume of activation, could be performed without acidic promoter under high pressure [58]. In this case, the major product is the syn hydroxy ketone, not as for the TiCl4-promoted reactions which lead mostly to the anti addition product. Since the syn or anti selectivity is the result of two transition states with different activation volumes (AV n < AVfnti), it was of great interest to investigate the aldol reaction in water. Indeed, the reaction of the silyl enol ether of cyclohexanone with benzaldehyde in aqueous medium was shown to proceed without any catalyst and under atmospheric pressure, with the same syn... 

The aldol reactions of the titanium Z-enolates proceeded smoothly with various aldehydes precomplexed with titanium chloride at -78° C. The diastereose-lectivity is high to excellent, with the single exception of benzaldehyde. The high degree of diastereoselection associated with this current asymmetric anti-aldol process can be rationalized by a Zimmerman-Traxler type of six-membered chairlike transition state Al9fl (Scheme 2.2r). The model is based on the assumptions that the titanium enolate is a seven-membered metallocycle with a chairlike conformation, and a second titanium metal is involved in the transition state, where it is chelated to indanolyloxy oxygen as well as to the aldehyde carbonyl in a six-membered chairlike transition-state structure. 

The influence of Lewis acids on the diastereoselectivity of the cycloaddition of /f-alkoxyalde-hydes has also been studied35. Magnesium bromide, highly effective for a-alkoxyaldehydes, fails in the case of the cycloaddition of aldehyde 10 to diene 2 and the reaction does not exhibit any selectivity, probably due to a change of mechanism to Mukaiyama s aldol type. One reason may be the change of solvent from tetrahydrofuran to a mixture of benzene and diethyl ether. The additions of aldehyde 10 to other dienes are more selective but diastereoselectivity is still much lower than for the a-alkoxy aldehydes. Boron trifluoride-diethyl etherate complex also leads to a mixture of four possible products. Excellent selectivity is achieved for the titanium(IV) chloride catalyzed addition of aldehyde 10a to diene 2b, 11c is obtained as the only product. 

A titanium(iv) chloride mediated Baylis-Hillman-type or aldol reaction between a-ketoesters and cyclohex-2-enones has been studied (Equation (13)).77 The steric effect of the R2 substituent is crucial for the reaction pathway since the aldol reaction only proceeds with the unsubstituted cyclohexenone (aldol adduct 71 with R2 = H to a small extent the Baylis-Hillman reaction occurs), whereas with the substituted substrate (R2 = Me) gives exclusively the Baylis-Hillman adduct 72. 

A limitation of the methylenation of carboxylic acid derivatives with Tebbe-type reagents such as 3 and 11 is that highly electrophilic acid anhydrides and acid halides cannot be transformed to the corresponding enol esters or alkenyl halides. The reaction of titanocene-methylidene generated from 11 with add chlorides results in the formation of acylation products via titanium enolates 12 [44] rather than methylenation. Since the titanium enolates 12 are stable and do not isomerize to the more highly substituted enolates, they are useful for regioselective aldol reactions (Scheme 4.11) [44a]. Although similar titanium enolates are also produced... 

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