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Ortholithiation directing groups

Addition of a lithiated secondary amine to an aldehyde both protects the aldehyde from attack by RLi and turns it into an ortholithiation directing group. The best lithioamines for this purpose are A-lithio-A-methylpiperazine 53, iV-lithio-iV,iV,iV -trimethylethylene-diamine 56 and Al-lithio-Al,0-dimethylhydroxylamine 58 , which optimize the opportunity for coordination of BuLi to the intermediate alkoxide (54) (Scheme 27) . ... [Pg.515]

In his review of 1990,104 Snieckus divided the typical ortholithiation-directing groups into classes, according to the ease with which they may be lithiated and the practicalities of their application in synthesis. It is clear that in the meantime certain metallation-directing groups have remained little more than curiosities, while others have become widely used. In this section, we shall survey metallation-directing groups in broad assemblies which share certain features. [Pg.34]

Coordination to strongly orf/zo-directing groups is responsible for the regiochemistry of some other reactions which do not involve ortholithiation. For example, while the electron-withdrawing nature of the oxazoline would be expected to direct the addition of the organolithium nucleophile to benzyne 11 towards the meta position, the major product that arises is the result of addition at the ortho position to give 12 (Scheme 1). ... [Pg.501]

To summarize, ortholithiation is a reaction with two steps (complex-formation and deprotonation) in which two features (rate and regioselectivity of lithiation) are controlled by two factors (coordination between organolithium and a heteroatom and acidity of the proton to be removed). In some cases, some of these points are less important (acidity, for example, or the coordination step). The best directing groups tend to have a mixture of the basic properties required for good coordination to lithium and the acidic properties required for rapid and efficient deprotonation. [Pg.502]

Double ortholithiation (to give a dUithiated ring) is usually feasible when two separate directing groups are involved, but using one group to direct simultaneously to both ortho positions usually fails . Simultaneous triple lithiation has never been achieved even with three separate groups . [Pg.505]

Even sulphonate esters 109 are powerful directing groups, competing well with tertiary amides. No substitution accompanies ortholithiation of ethyl or isopropyl benzene-sulphonate by BuLi. Hydrolysis and chlorination of the products 110 gives functionalized sulphonyl chlorides 111 (Scheme 48) °°. [Pg.526]

It is just about possible to ortholithiate imines, but in nearly all cases, the side reaction of nucleophilic attack at C=N is at least as important. Ortholithiation can overcome this side-reaction if it is assisted by an additional directing group (Scheme 58) . ... [Pg.529]

The usually very powerfully ortto-directing groups such as secondary carboxamide surprisingly do not always lead to ortholithiation on pyrazine and pyridazine rings lithi-ation of 253 and 254, for example, takes place principally (at least kinetically) at the meta and para positions (Scheme 125) . ... [Pg.559]

The greater acidity of lateral protons means that LDA can usually be used to remove them and hence much more electrophilic directing groups can be used for lateral lithiation than ortholithiation. Ethyl 2-methylbenzoate 427 is deprotonated at -78 °C by LDA but as soon as the product organolithium forms it adds to unreacted starting material to give dimeric products 428.392... [Pg.78]

The total synthesis of veiutamine [53], which has a carbon side chain and a structure similar to makaluvamine D, has also been achieved via route a (Scheme 6). The 6-methoxyindole derivative 9 was converted to the Boc compound 11. Regio-selective ortholithiation at 6-position using the Boc group as a directing group and coupling with an aldehyde followed by intramolecular cyclization afforded the tetracyclic compound 12, which was converted to veiutamine [54]. [Pg.138]

Ferrocene is best deprotonated by f-BuLi/f-BuOK in THF at 0 since BuLi alone will not lithiate ferrocene in the absence of TMEDA and leads to multiple lithiation in the presence of TMEDA. In the example in Scheme 134, a sulphur electrophile and a Kagan-Sharpless epoxidation lead to the enantiomerically pure sulphinyl ferrocene 278. The sulphinyl group directs stereoselective ortholithiation (see Section I.B.2), allowing the formation of products such as 279. Nucleophilic attack at sulphur is avoided by using triisopropylphenyllithium for this lithiation. [Pg.564]

The amide 504 may be made by ortholithiation of benzodioxolane 505, though a higher-yielding preparation starts from 1,2-dihydroxybenzoic acid 506. OrthoUthiation of 504, directed by the tertiary amide group, is straightforward, and gives the alkylated amide 503 (Scheme 196). [Pg.602]

Tertiary amides can direct vinylic lithiations in the manner of ortholithiations as shown by the example of 605 and 606. Even methyl groups can be lithiated given an appropriate director and base 607 forms the cyclopropane 609 on treatment with 608 in refluxing heptane (Scheme 238). ... [Pg.622]


See other pages where Ortholithiation directing groups is mentioned: [Pg.275]    [Pg.275]    [Pg.70]    [Pg.497]    [Pg.505]    [Pg.514]    [Pg.540]    [Pg.597]    [Pg.28]    [Pg.33]    [Pg.35]    [Pg.35]    [Pg.73]    [Pg.225]    [Pg.564]    [Pg.497]    [Pg.498]    [Pg.500]    [Pg.502]    [Pg.527]    [Pg.610]    [Pg.28]    [Pg.30]    [Pg.31]    [Pg.32]    [Pg.50]    [Pg.81]    [Pg.126]    [Pg.367]   


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Directing groups

Ortholithiation

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