Regioselectivity alkylation

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 transition metal-catalyzed allylation of carbon nucleophiles was a widely used method until Grieco and Pearson discovered LPDE-mediated allylic substitutions in 1992. Grieco investigated substitution reactions of cyclic allyl alcohols with silyl ketene acetals such as Si-1 by use of LPDE solution [95]. The concentration of LPDE seems to be important. For example, the use of 2.0 M LPDE resulted in formation of silyl ether 88 with 86 and 87 in the ratio 2 6.4 1. In contrast, 3.0 m LPDE afforded an excellent yield (90 %) of 86 and 87 (5.8 1), and the less hindered side of the allylic unit is alkylated regioselectively. It is of interest to note that this chemistry is also applicable to cyclopropyl carbinol 89 (Sch. 44). 

Lower dialkylboranes are reactive and hydroborate alkenes rapidly, even without a solvent below 0°C. The reactivity depends on the alkyl group, decreasing primary > secondary > cyclo-alkyl. Regioselectivity approaches that of RjBH with bulky substituents. Unfortunately, mixtures of products are formed because the reagents disproportionate and are in equilibrium with R3B and alkylated diboranes ... 

The enolate of enone 94 was alkylated regioselectively using 4-iodo-l-(tert-butyldiphenylsiloxy)butane to afford a 2.5 1 mixture of diastereomers 121a and 121b in 77% yield. The mixture of diastereomers were separated and the major product was carried forward. Decoupling... 

Two sohd-phase syntheses of Af-hydroxy(alkoxy)indoles have been reported by Roy (equation 1) [91] and Wu (equa-tion2) [92] respectively (Scheme 15).TheAf-hydroxyindoles in equation 2 were alkylated regioselectively to give a library of 1,2-dialkoxyindoles after cleavage from the SynPhase lanterns [92]. In a program toward the synthesis of the alkaloids avrainvillamide and stephacidin B, Myers and Herzon synthesized 3-alkylidene-3//-indole 1-oxide (equation 3), which is the keystone unit of these novel alkaloids [93]. 

The high regioselectivity of tetrazolate 97 alkylation in the environment of aqueons acetone giving predominantly the 2H-isomer was later noted also by Spear et al. [100]. 5-Trifluoromethyltetrazole 96 slowly reacts with formaldehyde in water solution at pH 5 giving 2-hydroxymethyl-5-trifluoromethyltetrazole 108 [101]. Later the role of the electronic effects of the substituents at the endocyclic carbon of the tetrazole, and also the influence of the solvation effects on the alkylation regioselectivity of tetrazoles was treated in detail in quite a number of theoretic and experimental pubhcations [28,102]. 

The anion from 3-methylpentadienyl-lithium exists substantially in the conformation (32), and is a useful reagent for introducing a diene unit common to several terpenoid species. Thus, reactionof(32)withR COR gives (33). 1,3-Dilithioalkynes are alkylated regioselectively at the 3-position and can then be reacted with another electrophile at the 1-position. ... 

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