Aldehydes titanium reagents

Stereoselectivities of 99% are also obtained by Mukaiyama type aldol reactions (cf. p. 58) of the titanium enolate of Masamune s chired a-silyloxy ketone with aldehydes. An excess of titanium reagent (s 2 mol) must be used to prevent interference by the lithium salt formed, when the titanium enolate is generated via the lithium enolate (C. Siegel, 1989). The mechanism and the stereochemistry are the same as with the boron enolate. 

Alkene Y Titanium Reagent X Aldehyde R d.r. (antijsyn) Yield (%) Ref... 

The enantiomeric compositions of the titanium reagents are monitored easily by the reaction with enantiomerically pure chiral aldehydes, such as 2-(fer/-butyldimethylsilyloxy)propanal104. Here, the ratio of diastereomeric products reflects the ratio of enantiomers of the reagent, although a small error arises from double stereodifferentiation95 104. 

Very high levels of induced diastereoselectivity are also achieved in the reaction of aldehydes with the titanium enolate of (5)-l-rerr-butyldimethylsiloxy-1-cyclohexyl-2-butanone47. This chiral ketone reagent is deprotonated with lithium diisopropylamide, transmetalated by the addition of triisopropyloxytitunium chloride, and finally added to an aldehyde. High diastereoselectivities are obtained when excess of the titanium reagent (> 2 mol equiv) is used which prevents interference by the lithium salt formed in the transmetalation procedure. Under carefully optimized conditions, diastereomeric ratios of the adducts range from 70 1 to >100 1. 

The titanium reagent also dimethylates aromatic aldehydes." Triethylaluminum reacts with aldehydes, however, to give the mono-ethyl alcohol, and in the presence of a chiral additive the reaction proceeds with good asymmetric induction." A complex of Me3Ti-MeLi has been shown to be selective for 1,2 addition with conjugated ketones, in the presence of nonconjugated ketones." ... 

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. 

Aldol-type reaction of zinc esters. This titanium reagent promotes condensation of (ethoxycarbonylalkyl)iodozinc compounds (13, 220) with aldehydes or ketones to provide hydroxy esters and/or lactones. The active reagent may be (ethoxycarbonyl)alkyltriisopropoxytitanium. 

Addition of propargylic and allenic titanium reagents to aldehydes. 

Propargylic ethers undergo directed lithiation and subsequent transmetallation to afford oxygenated allenyl titanium reagents. Subsequent addition of aldehydes gives rise to various homopropargylic alcohol adducts as mixtures favoring the anti dia-stereomers (Tables 9.18 and 9.19) [29, 30]... 

Deprotonation of 3-methoxy-3-methylallene with BuLi followed by metal exchange with Ti(OiPr)4 affords a chiral allenyltitanium reagent [31], Addition of this reagent to enantioenriched (S)-2-benzyloxypropanal afforded a mixture of four diastereomeric products in which the anti,syn and anti,anti adducts predominated (Eq. 9.26) [31], The former was shown to derive from the matched pairing of the (S)-aldehyde with the (P)-enantiomer of the allenic titanium reagent. The latter is the major diastereomer of the mismatched (S)/(M) pairing. 

An alternative, but related, route to allenic titanium reagents from propargylic esters has been reported recently. Reaction of titanocene dichloride with BuMgCl and Mg yields a reactive titanocene intermediate, formulated as Cp2Ti. This reduced Ti species reacts in situ by oxidative addition to propargylic acetates. The allenyltitanium reagents thus produced add to aldehydes and ketones, as expected, to afford homopropargylic alcohols (Table 9.27) [43]. 

The chiral titanium reagent preparerd in situ from the chiral 1,4-diol and dichlorodiisopropoxytitanium is expected to be applicable to various reactions catalyzed by Lewis acids. We, therefore, investigated the asymmetric synthesis of cyanohydrins from aldehydes and cyanotrimethylsilane employing the chiral titanium reagent.(20)... 

Simple diastereoselectivity comes into play when allenylmetal compounds are added to aldehydes, since adducts such as 1 a/b contain both an axis and a center of asymmetry. Hence, diastereomeric mixtures are produced. When chiral aldehydes are used in such reactions, the diastereoselectivity also depends on the relative rate by which the enantiomers of the racemic allenylmetallic species interconvert, i.e., relative to the rate of addition to the chiral aldehyde. Apart from reactions of allenyllithium and -titanium reagents with aldehydes90-94, few such intermolecular, simple diastereoselective reactions yielding allenes have been reported. 

The titanium reagent also dimethylates aromatic aldehydes.372... 

Preparation Essentially this reaction involves the preparation of a low-valent titanium reagent that then couples carbonyl groups, including esters to aldehydes/ketones. Generally, TiCLt is reduced with some reducing agent (LiAIH4, Zn, Mg). 

Dienes.1 The titanium reagent 2, obtained from 1 by metallation and reaction with Ti(0-/-Pr)4, reacts with aldehydes to give (3-triphenylsilyl alcohols (3). These can be converted into either (E)- or (Z)-l,3-dienes by treatment with acid or base. 

Diastereospecific aldol condensations,u The titanium enolate of the chiral ketone 1 reacts with aldehydes to give mainly the syn-aldol (—90 10). However, use of excess titanium reagent or addition of 12-crown-4 (which complexes Li+) results in >99 1 diastereoselectivity. 

Apart from the Takai method and titanium reagents such as 15, silyl reagents 16 and 17 frequently find application in the synthesis of vinylic silanes from carbonyl compounds. Reagent 16 can be utilized with aldehydes and non-enolizable ketones in a reaction analogous to the Peterson olefination Reagent 17 also reacts successfully with enolizable ketones.6... 

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