Bis alkoxytitanacyclopropanes and -propenes (Kulinkovich reagents): Versatile reagents for carbon—carbon bond formation

The Chemistry of Cyclopropanols

“…This work has been reviewed recently. [64][65][66][67][68] 1-Substituted cyclopropanols were formed in moderate yields when carboxylic esters were treated with 1,4-di(bromomagnesium)butane in the presence of titanium(IV) isopropoxide. 68 This transformations is thought to involve a rearrangement of the titanacyclopentane intermediate 33 into the respective bisethylenic complex 34, which is then converted into 1-substituted cyclopropanol 19 (Scheme 16) in the manner described above (Scheme 9).…”

π-1,1-Dimethyleneallylmetal and Homologous Complexes: Their Application in Organic Synthesis

“…Addition of carboxylic acid esters to a mixture of titanium(IV) isopropoxide (1 equiv) and an alkylmagnesium bromide (3 equiv) at low temperature (−78 to 0 °C) affords 1-alkylcyclopropanols . This simple and efficient procedure could also be achieved in a catalytic version when the order of reagents was inverted, i.e., by addition of the Grignard reagent to the mixture of ester and titanium(IV) isopropoxide. 38a-e The intermediate diisopropyloxytitana(IV)cyclopropanes 45a and/or their (η 2 -olefin) diisopropyloxytitanium(II) resonance forms 45b have been considered to act as 1,2-dicarbanionic equivalents performing a 2-fold alkylation of alkoxy-carbonyl groups to provide diastereoselectively ( E )-cyclopropanols in good or excellent yields. 38a-c However, treatment of α,β-unsaturated esters 46 with Grignard reagents (e.g., EtMgBr or n- BuMgBr) in the presence of titanium(IV) isopropoxide [Ti(O i Pr) 4 ] (0.2−1.1 equiv) under various experimental conditions, gave the expected 1-ethenylcyclopropanols 47 in unusably low yields (<10−25%) . When the ( E )-1-styrylcyclopropanol 10a (R = H, R‘ = Ph), unequivocally prepared from the cyclopropanone hemiacetal magnesium salt 8 (Scheme ),7b was treated with EtMgBr/Ti(O i Pr) 4 , i.e., with the reagent 45a , b under the conditions of the cyclopropanation reaction, 38a-e then reductive elimination of the hydroxy group occurred to provide the (2-phenylethylidene)cyclopropane 47 in 95% yield (Scheme ) …”

5.34 Early Transition Metal Mediated Reductive Coupling Reactions

“…2 Like the established reactivity of the 'Negishi reagent' (n-Bu 2 ZrCp 2 ), 3,4 it has been proposed that the Kulinkovich reaction proceeds through the intermediacy of a similar metallacyclopropane, formed from decomposition of the initially formed (alkyl) 2 Ti(Oi-Pr) 2 species. 5 In short, each s C-Ti bond of the resulting metallacyclopropane engages in nucleophilic addition to the carboxylic ester, resulting in the formation of a hydroxycyclopropane. At the current time, more substantial data exist to support the sequence of events that proceed from (n-Bu) 2 ZrCp 2 to the corresponding butene-ZrCp 2 complex than the sequence of events that proceed from the R 2 Ti(Oi-Pr) 2 intermediate proposed in the Kulinkovich reaction.…”

“…Imine, ClTi(Oi-Pr)3 , c-C5 H 9 MgCl then sodium alkoxide of allylic alcohol (-40 °C to r.t.), then H 2 O 73% Imine-allylic alcohol coupling for the synthesis of indolizidines and quinolizidines. Aldehyde, LiHMDS, THF (-10 °C) then -78 °C, Ti(Oi-Pr) 4 , C 5 H 9 MgCl, (-78 to -30 °C), then Li-alkoxide of allylic alcohol C. Three-component coupling reaction for the synthesis of stereodefined primary homoallylic amines.…”