Transmetallation stereochemistry

The stereochemistry of the Pd-catalyzed allylation of nucleophiles has been studied extensively[5,l8-20]. In the first step, 7r-allylpalladium complex formation by the attack of Pd(0) on an allylic part proceeds by inversion (anti attack). Then subsequent reaction of soft carbon nucleophiles, N- and 0-nucleophiles proceeds by inversion to give 1. Thus overall retention is observed. On the other hand, the reaction of hard carbon nucleophiles of organometallic compounds proceeds via transmetallation, which affords 2 by retention, and reductive elimination affords the final product 3. Thus the overall inversion is observed in this case[21,22]. 

The reaction of phenylzinc reagent proceeds with opposite stereochemistry, namely by retention of configuration at the final step via transmetallation. Both the (S)-( )- and (i )-(Z)-allylic acetates 4 and 9 afford the (/ )-( )-phe-nylated product II by overall inversion[23]. 

The reaction is formulated as an electrophilic attack by the aluminum halide, followed by hydride abstraction and transmetallation. A vinyl cation intermediate can account for both the regiochemistry and the stereochemistry. 

The anti stereochemistry is consistent with a cyclic TS, but the reaction is stereocon-vergent for the E- and Z-2-butenylstannanes, indicating that isomerization must occur at the transmetallation stage. The adducts are equilibrated at 82 °C and under these conditions the anti product is isolated on workup. 

These reactions are believed to proceed via transmetallation. Configurational inversion occurs at both the transmetallation and addition steps, leading to overall retention of the allylic stereochemistry. 

Coleman established the hydroxypropyl stereochemistry via addition of a homochiral a-alkoxyalkyl organometallic species. This reagent was prepared in high enantiomeric excess using a Noroyi BINAL-H reduction of organostannane 33, which was transmetallated with ra-BuLi to achieve the desired organolithium reagent 35 (Scheme 7.5). Both enantiomers of 35 could be obtained via this route. 

A more satisfactory sequence, which also starts with enantioenriched propargylic mesylates, generates the allenylindium intermediate by oxidative transmetallation of an allenylpalladium precursor with Ini. This catalytic process takes place in the presence of an aldehyde. The reaction employs 5-10 mol% of the palladium catalyst and a stoichiometric quantity of Ini. Based on the stereochemistry of the starting... 

Transmetalations with first row transition metal elements such as titanium or manganese have produced useful synthetic applications. Organotitanate species of type 123 show the advantage of high Sn2 selectivity in the anti stereochemistry of the resulting copper(I) intermediates (Scheme 2.56) [119, 120],... 

Assuming that the transmetallation and subsequent reaction with allyl bromide do not alter the configuration of the carbon-zinc bond47, the stereochemistry of the intermediate is that shown for 85. Hence it follows that one of the two carbon-metal bonds in 84 has... 

Although ionization usually proceeds with inversion of stereochemistry regardless of the nucleophile, the addition of a nucleophile involves two pathways in which the nature of the nucleophile leads to different stereochemical consequences (Scheme 8E.2). The soft (stabilized) nucleophiles, defined as those derived from conjugate acids whose pA < 25, usually add to the allyl ligand from the side opposite to the metal, giving rise to product with overall retention of stereochemistry [21-23]. On the other hand, with hard (unstabilized) nucleophiles (pA a > 25), the addition normally occurs via transmetallation where the nucleophile attacks the metal center of the rc-allyl intermediate and the resultant adduct collapses to product by reductive... 

However, their nonstatistical distribution as well as retention of stereochemistry if alkenyl organometallics were used (see Scheme 10.14),12 suggested that free radicals were not intermediates in such reactions. Such Wurtz-type couplings therefore probably proceeded by transmetallation and then recombination (Scheme 10.1). 

It is essential, for successful retention of stereochemistry, to form the organolithiums by halogen-metal exchange, and not by reductive lithiation. While transmetallation of cis- and trans-24 with BuLi, quenching the organolithium 25 with ethylene oxide, gives complete retention of stereochemistry in 26. Owing to the intervention of radicals, reductive lithiation leads to considerable (but not total) epimerisation ... 

Corey exploited the remarkable configurational stability of cyclopropyllithiums in his synthesis of hybridalactone. The stannane 28 was made by Simmons-Smith cyclopropanation of the allylic alcohol 27 and resolved by formation of an O-methyl mandelate ester. Transmetallation of 29 with 2 equiv. BuLi gave an organolithium which retained its stereochemistry even in THF over a period of 3 h at 0 °C, finally adding to 31 to give 32. 

The trimethylstannanes, on the other hand (which can be transmetallated at -120 °C in methyl THF) each give a ratio of products reflecting the stereochemistry of the starting material. The stereospecificity of the reactions indicates considerable configurational stability in these a-seleno organolithiums at -120 °C. The same ratios are obtained after 3 h or 6 h, indicating that the epimerisation takes place during the exothermic addition of the methyllithium. 

Similarly, the stannane 334 transmetallates with apparent stereospecificity and the product organolithium 335 reacts with overall retention.156 The origin of stereochemistry in the product can only be assumed here because of the unknown role of chelation by the -OLi group. 

Previous work5 6 had shown that, overall, transmetallation-electrophilic quench via vinyllithiums proceeds with retention or stereochemistry, and Seyferth s work4 finally proved that each of the two steps in the sequence are retentive. 

The synthesis of 9-alkenyl-9-BBN via hydroboration of terminal alkynes with 9-BBN suffered from the formation of 1,1-diborylalkanes via dihydroboration along with desired monohydroboration products. Alternatively, selective monohydroboration of terminal alkynes with dicyclohexylborane was followed by transmetallation with 9-MeO-9-BBN (Equation (193)).710 Treatment of the hydroboration intermediates with DIBAL-H in the presence of a borane-trapping reagent such as 1-hexene gave 1-alkenylaluminum compounds with complete retention of the (E)-stereochemistry (Equation (194)).711... 

The transmetallation step (iii) is certainly the most enigmatic part of the catalytic cycle. Generally, it is assumed to be rate limiting, and several mechanisms are proposed depending on the solvent. An open transition state with inversion of the stereochemistry would arise with polar solvents which are able to stabilize the transient partial charges , whereas a cyclic transition state with retention of the stereochemistry would arise in less polar solvents. It should be noted that the nature of the ligands on the palladium may influence dramatically the kinetics of the transmetallation step. A 1000-fold rate enhancement was observed when replacing triphenylphosphine by tri(2-furyl)phosphine . However, the dissociative or associative nature of the substitution on the palladium is stiU under discussion . ... 

Stannyl- (and -silyl-) carboxylic acids undergo oxidative decarboxylation with LTA under mild conditions to provide the corresponding alkenes. This represents an improvement on the well-known alkene-forming decarboxylation of acids with LTA, which requires thermtd or photochemical conditions, for example. The directing metal effect leads to improved yields and regioselectivity. However, stereo-specific alkene formation did not occur and this could imply free radical involvement or transmetallation (Pb for Sn) (stereochemistry ) followed by cation formation, see for example Scheme 27. 

Alkenyllithium compounds can also be prepared by metaUation of alkenes, particularly when alkenyl hydrogens are rendered acidic by an a-substituent (equation 22). Transmetallation of alkenyl stannanes with organohthium reagents gives alkenyUithium compounds with retention of alkene stereochemistry (equation 23). Tin lithium fransmet-allation has been used to prepare 1,4-dihthio-l,3-butadiene. Monosubstituted alkenylhthium compounds RHC=CHLi, can also be prepared from the corresponding diorganotel-luride, RHC=CHTeBu, by reaction with butylhthium in... 

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