Alkylmagnesium derivatives

Moreover, the use of alkylmagnesium derivatives has been shown to be more satisfactory in some cases, as exemplified by the results shown in Scheme 67105. 

Alkylaluminum derivatives Alkylmagnesium derivatives Alkyl nonmetal halides Complex anhydrides Metal halides (some)... 

The reaction of primary and secondary alkylzinc and alkylmagnesium derivatives with alkenyl halides, such as ( )-l-iodo-2-methy-l-hexene, in the presence of 5mol% of PdCPPhj) can proceed to give the desired cross-coupling products in good yields along with only minor amounts (<15%) of the deiodination products [66,67] (Table 1-2). A closer look at the reaction of ec-BuMgCl with ( )-PhCH=CHBr catalyzed by various Pd-phosphine... 

For a study of zirconocene-catalyzed alkene carbomagnesiation with longer alkylmagnesium derivatives, see Rousset, C.J., Negishi, E., Suzxiki, N., and Takahashi, T. (1992) Tetrahedron Lett., 33, 1965-1968. 

The aforementioned observations have significant mechanistic implications. As illustrated in Eqs. 6.2—6.4, in the chemistry of zirconocene—alkene complexes derived from longer chain alkylmagnesium halides, several additional selectivity issues present themselves. (1) The derived transition metal—alkene complex can exist in two diastereomeric forms, exemplified in Eqs. 6.2 and 6.3 by (R)-8 anti and syn reaction through these stereoisomeric complexes can lead to the formation of different product diastereomers (compare Eqs. 6.2 and 6.3, or Eqs. 6.3 and 6.4). The data in Table 6.2 indicate that the mode of addition shown in Eq. 6.2 is preferred. (2) As illustrated in Eqs. 6.3 and 6.4, the carbomagnesation process can afford either the n-alkyl or the branched product. Alkene substrate insertion from the more substituted front of the zirconocene—alkene system affords the branched isomer (Eq. 6.3), whereas reaction from the less substituted end of the (ebthi)Zr—alkene system leads to the formation of the straight-chain product (Eq. 6.4). The results shown in Table 6.2 indicate that, depending on the reaction conditions, products derived from the two isomeric metallacyclopentane formations can be formed competitively. 

In the hydroxycyclopropanation of alkenes, esters may be more reactive than N,N-dialkylcarboxamides, as is illustrated by the exclusive formation of the disubstituted cyclopropanol 75 from the succinic acid monoester monoamide 73 (Scheme 11.21) [91]. However, the reactivities of both ester- as well as amide-carbonyl groups can be significantly influenced by the steric bulk around them [81,91]. Thus, in intermolecular competitions for reaction with the titanacydopropane intermediate derived from an alkylmagnesium halide and titanium tetraisopropoxide or methyltitanium triisoprop-oxide, between N,N-dibenzylformamide (48) and tert-butyl acetate (76) as well as between N,N-dibenzylacetamide (78) and tert-butyl acetate (76), the amide won in both cases and only the corresponding cyclopropylamines 77 and 79, respectively, were obtained (Scheme 11.21) [62,119]. 

Aldehyde imines derived from alkoxyamines are metalated by LDA (0 °C, TIIF, 1 h6 or —23 °C, THF, 0.5 h13) and by potassium diethylamide, lithium bis(trimethylsily])amide and lithium 2,2,6,6-tetramethylpiperidide (—23 °C, THF, 2-4 h)1J. Nucleophilic bases such as alkyl- and aryllithium derivatives and, in some cases, alkylmagnesium bromides add to aldehyde imines. Best enantioselectivities are achieved with lithium 2,2,6,6-tetramethylpiperidide (LTMP)13. The... 

A useful application of organomagnesium amides is in the enantioselective conjugate addition to enamidomalonate to prepare /3-amino acid derivatives (Scheme 16). The alkylmagnesium amide complexes provided both high yields and high selectivity in the organic transformation. 

Metallation of alkynylcyclopropanes at the acetylenic end is accomplished either by deprotonation or via metal-halide exchange reaction with strong bases. Metallation of ethynylcyclopropane may be affected by KOH in DMF, ethereal EtMgBr or preferably BuLi in THF (equation 151)231. All three metal acetyl ides react with methyl ketones to give the corresponding alcohols. However, the instability of cyclopropyl ketones towards bases, especially at the reaction conditions required by KOH (20 °C, 6h), and the sensitivity of cyclopropenyl double bonds in cyclopropenyl ketone derivatives towards addition reactions of alkylmagnesium compounds, make the alkyllithium (-78 °C, instant reaction) superior to the other reagents. 

Reaction of 2-benzo[6]thienyllithium (and its 7-methyl derivative 90) with aldehydes 486,5fl4, 620 or ketones 467 483 affords a secondary or tertiary alcohol, respectively. Treatment of 2-benzo[6]thienyl-lithium with acetyl chloride gives mainly l,l-di(2-benzo[6]thienyl)-ethylene.132 Side-chain alcohols in positions other than the 2-position are most easily prepared by reaction of the appropriate benzo[6]-thienylmagnesium halide with aldehydes 460,471 or ketones,186,3o9, 349, 4 7,466,479,498 or foy reaction of a benzo[fe]thiophene aldehyde, ketone, or ester with an alkylmagnesium halide.358,427 465 The preparation of alcohols from 2- and 3-benzo[6]thienylmethyl-magnesium chloride485,528 is discussed in Section VI, D, 4. 

Note, however, that with alkyl sulfoxides or alkylmagnesium halides, products derived formally from loss of SO may be obtained [34] (see also Ref. [35]) ... 

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