Alkylation regioselective

Deprotonation of / /-cyclohexylfluoroacetone imines by lithium hexamethyl-disilazide or tertiary butyl lithium at very low temperature allows a regioselective alkylation at the carbon carrying fluorine [773] (equation 98). 

A synthesis of aldehydes developed by Meyers begins with the commercially available dihydro-1,3-oxazine derivatives 132 (A = H, Ph, or COOEt). Though the ions (133) prepared from 132 are ambident, they are regioselectively alkylated at... 

Hence ketone (1) might be made by regioselective alkylation of (2) but this is doubtful. A safer route is to disconnect the ethyl group to leave nitrile (3) which can certainly be made by alkylation of nitrile (4) as there is only one site for enolisation. 

The regioselective alkylation and acylation of 3,5-diamino-l,2,4-triazole 19 using a simple protecting group strategy has been described in detail <2006RJA624, 2006ZPK632>. 

The electrochemical oxidation of l-MeO-7-alkyl-CHT in MeOH yields 2-alkyltropones, while the thermal rearrangement of 3-MeO-7-alkyl-CHT to l-MeO-4-alkyl-CHT followed by its anodic oxidation in MeOH affords 4-alkyltropones (equation 21). l-MeO-7-alkyl-CHT is prepared by the regioselective alkylation of 7,7-diMeO-CHT with a Grignard reagent and Cul, while 3-MeO-7-alkyl-CHT is also regioselectively prepared by alkylation of 7,7-diMeO-CHT with an alkyl lithium. 

The anionic intermediates generated by the cathodic reduction of CHT and some of its derivatives such as 1-MeO- and 3-MeO-CHTs are regioselectively alkylated with alkyl halides to give 6-alkyl-l,3-cycloheptadiene and l-MeO-6-alkyl-l,3-cycloheptadiene as the main products, respectively21. 

The synthetic usefulness of dioxin vinylogous esters as p-keto vinyl cation equivalents was demonstrated by a variety of reductive and alkylative 1,3-carbonyl transpositions.5 7 Regioselective alkylation and hydroxylation at the a -position (and, in some cases, at the y-position)8 9 further extend the usefulness of 1,3-dioxin vinylogous ester templates in organic synthesis. 

Electrogenerated bases (see Chap. 14) can be prepared in situ and tailored for regioselective deprotonation. Regioselective alkylation of an unsymmetrical cyclic ketone was achieved by using an electrogenerated triphenylmethyl anion (Eq. 5, RX = CH3I,... 

Takeo, K. Shibata, K., Regioselective Alkylation, Benzoylation, and Para-Toluene Sulfonylation of Methyl 4,6-0-Benzylidene-Beta-D-Glucopyranoside. Carbohydr. 

Coldham and coworkers have shown that the asymmetric deprotonation protocol can be used to regioselectively alkylate the 5-position of imidazolidines (Scheme 35). The process is used as part of a sequence that results in asymmetric alkylation of 1,2-diamines with high stereoselectivity. The yields are limited, in this case, by the barrier to rotation around the carbamate C—N bond. Thus, only the amide rotamer having the carbonyl group syn to C-5 of the heterocycle is deprotonated. There are several examples in this review where this limitation is possible whether it is a factor or not may depend on the temperature at which amide bond rotation occurs versus the stability of the organolithium compound. In this case, the barrier to amide bond rotation was determined as 16.6 kcalmoD at 60 °C. 

The parent thieno[3,4- ]-l,2,4-thiadiazine dioxide 35 undergoes regioselective alkylation at N-2 to give, for example, compound 36. This can then be followed by alkylation at N-4 (Scheme 7) <1999BMC2811, 2000EJM751>. 

The regioselective alkylation of [1,6]- and [l,7]-naphthyridines using benzylstannane and ethyl chloroformate has been described <2000TL8053> as an excellent route to give substituted dihydronaphthyridines (Scheme 4). 

The phosphine oxide (-)-(5 )-[2-(dimethylamino)ethyl]methyloxophenylphosphorane85 was treated with butyllithium or LDA to give, via directed lithiation, the methylene-deprotonated compound regioselectively. Alkylation with bromomethylbenzene gave (S)-[l-benzyl-2-(di-methylamino)ethyl]methyloxophenylphosphorane with low diastereoselectivity (d.r. 55 45)86. 

The reduction of a,/ -unsaturated ketones, e.g., 7, by lithium in ammonia is another possibility for generation of enolates19. This method has been mainly used in the preparation of enolates for stereo- and regioselective alkylations in the steroid and terpenoid fields (see... 

Regioselective alkylative opening of a,(1-epoxy ketone oxime [40] and tosylhydra-zones [41] with organocopper reagents is initiated by the generation of unsaturated azo compounds which undergo conjugate addition. 

Regioselective alkylation of a methyl ketone Even though the kinetic enolate of 2-heptanone consists of a mixture of terminal and internal enolates in the ratio 87 13, benzylation in DME results in preferential internal alkylation. Regioselective benzylation at the terminal position can be enhanced by addition of various ligands such as benzo-14-crown-4 and DMF, but HMPT is the most effective ligand, resulting in a ratio of terminal to internal benzylation of 11 1. The three ligands also increase the rate of alkylation. The same effect, but less marked, is observed in alkylation with the less reactive electrophile butyl iodide. 

The direct a-alkylation of monoketones normally employs reaction of an alkyl halide or sulfonate with the enolate anion produced using a strong base. This method can be satisfactorily used with symmetrical ketones, which are to be dialkylated with a dihalide, and with intramolecular cyclization reactions, where the formation of five- and six-membered rings is often favored over the formation of three-, four-, seven-, and eight-membered rings (M. Mous-seron, 1937 W.S. Johnson, 1963). Regioselective alkylation of dianions according to Hauser s rule (see p. 9f.) is usually also a satisfactory procedure (F.W. Sum, 1979). 

Another new LDA-based strategy for regioselective alkylation of unsymmetrical ketones involves the combined use of LDA and aluminium tris(2,6-diphenylphen-oxide) the latter complexes the less hindered side of the ketone, blocking the LDA and re-directing it by default to the more hindered side.154... 

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