Nucleophilic capture stereoselectivity

A deuterium-labeling study of a reaction of this type demonstrated syn stereoselectivity in both the oxypalladation and P-elimination, which indicates that the cyclization occurs by internal migration, rather than by an anti nucleophilic capture.113 This particular system also gives products from double-bond migration that occurs by reversible Pd(II)-D addition-elimination. 

No reactions of t with protic solvents have been reported however, its cyclic analogue 1,2-diphenylcyclobutene (7) reacts with the protic solvents methanol, acetic acid, and water, to yield adducts 85 and 86 (eq. 28). The proposed mechanism for the formation of 85 and 86 involves the formation of singlet exciplex followed by proton transfer to yield a cyclobutyl cation 87. Stereoselective nucleophilic capture of 87 by solvent from its less hindered side yields 85, while skeletal rearrangement of 87 yields the cyclopropylmethyl cation 88, which reacts with solvent to yield 86 ... 

Significant insights into the nature of the nucleophilic capture of radial cations is provided by the regiochemistry of the attack on the bridged norcaradiene radical cation, 18 +. The products suggested regiospecific attack of methanol on 18"+ with capture at C2 and C5 generating 104" and 105". The attack occurs with limited stereoselectivity, because products derived from 104" and 105" were formed in comparable yields [131]. 

PouLTER has demonstrated that chrysanthemyl derivative 16-OPy I asymmetrically deuterated at the carbinyl position ionizes with 91 2% stereoselectivity from a conformation with the leaving group aligned antiparallel to the 1,3-cyclopropyl bond (68). Since rotation about the C1-C2 bond in the cyclopropylcarbinyl carbonium ion intermediate should be slow relative to nucleophilic capture, this selectivity is reflected in the position of the deuterium atom in the vinyl group of the two major products. The stereoselectivity is attributed to stabilization of the transition state for ionization by charge delocalization into the vinyl group which should be more favorable in the a/i/f-parallel alignment. Kinetic data also indicate that the double bond facilitates the ionization process. 

Similar schemes can be developed easily for analogous reactions of acceptor-substituted polyenes. For example, a triene with an acceptor group in 1-position can form six regioi-someric products of Michael addition and electrophilic capture, and each of these exists as E/Z stereoisomers, diastereomers and/or enantiomers. Thus, reactions of this type are only useful if both the regio- and stereoselectivity can be controlled fortunately, only one isomeric Michael adduct is formed in many cases. This is true in particular for polyunsaturated Michael acceptors which bear at least one triple bond besides one or more double bonds. An additional feature of the latter substrate type is that nucleophilic additions can... 

As in the case of addition reactions of carbon nucleophiles to activated dienes (Section HA), organocopper compounds are the reagents of choice for regio- and stereoselective Michael additions to acceptor-substituted enynes. Substrates bearing an acceptor-substituted triple bond besides one or more conjugated double bonds react with organocuprates under 1,4-addition exclusively (equation 51)138-140 1,6-addition reactions which would provide allenes after electrophilic capture were not observed (cf. Section IV). 

Intramolecular capture of the nucleophile provides heterocycles (equation 15). The regio- and stereoselectivity of this process, which is highly dependent on the substrates and conditions, have been investigated" . 

It should be pointed out that in nucleophilic reactions, where the second step is protonation, as well as in the capture of the carbocation formed in the course of electrophilic reactions with bicyclobutane, the reactive intermediates are preferentially trapped from an equatorial direction. A priori, there is no obvious stereoelectronic driving force for this exceptional behavior of the reaction of PhSH with 60. However, in this specific case, it could stem from a steric repulsion between the methylene group at position 4 of the tricyclic system and the phenyl group of the PhS either entering or already present. Supporting this assumption are reactions of thiyl radical with bicyclobutane (equation 85) " . In the absence of the steric effects of the tricyclic system, the cis and trans isomers were obtained in equal amounts. Hence, at this stage, it seems that unlike the reactions of cyclobutyl carbanion or carbocation, stereoselectivity in the trapping radical... 

The hallmark of a concerted process is stereoselectivity. Crich and Gastaldi investigated the cine substitution reaction with the diastereomeric probes 27 and 28 and found partial (i.e. incomplete) scrambling in the products 29 and 30 (Scheme 26) [50], This result is best interpreted in terms of the evolving general mechanistic picture and stereoselective capture of the two diastereomeric contact or solvent-separated ion pairs by the nucleophile. The possibility remains, however, of a concerted mechanism in which the nucleophile does not distinguish between the two lobes of the singly occupied p-orbital in the initial radical. 

Nucleophilic solvents compete with bromide, but anti stereoselectivity is still observed, except when ERG substituents are present. It is proposed that anti stereoselectivity can result not only from a bridged ion intermediate, but also from very fast capture of a carbocation intermediate. Interpretation of the ratio of capture by competing nucleophiles has led to the estimate that the bromonium ion derived from cyclohexene has a lifetime on the order of 10 ° s in methanol, which is about 100 times longer than for secondary carbocations. ... 

Ma has developed a three-component allene carboamination reaction for the stereoselective synthesis of 2,5-as-disubstituted pyrrolidine derivatives [54]. A representative transformation involving allene 58, 4-iodoanisole, and imine 59 that generates 60 in 90% yield is shown below (Eq. (1.28)). The reaction is believed to proceed through the intermediate Jt-allylpalladium complex 62, which is formed by carbopalladation of the alkene to give 61 followed by addition of the malonate anion to the activated imine. Intramolecular capture of the allylpalladium moiety by the pendant nitrogen nucleophile affords the pyrrolidine product. A related asymmetric synthesis of pyrazolidines that employs azodicarboxylates as one of the electrophilic components has also been reported [55]. The pyrazolidine products are obtained with up to 84% ee when chiral bis oxazolines are employed as ligands. 

Backvall and coworkers have developed a stereoselective palladium catalyzed 1,4-addition to cyclic 1,3-dienes that produces pyrrolidine [89a] or lactam products [89bj. For example, treatment of 123 with catalytic Pd(OAc)2 and excess LiCl affords 125 (Eq. (1.50)). Alternatively, treatment of 123 with catalytic Pd(OAc)2 and excess LiOAc affords 127 (Eq. (1.51)). Both reactions proceed via awti-aminopalladation to afford an allylpalladium complex (124 or 126), which is then captured by an external nucleophile. Outer-sphere attack of chloride ion on 124 results in net syn-addition to the diene to give 125, whereas inner-sphere attack of acetate results in anti-addition to provide 127. 

The N -acetylneuraminic acid derivative (63) was converted via the iV-nitroso-derivatives (64) into the diazo-intermediate (65) which was then captured with nucleophilic reagents to give the azide (66) or the KDN (3-deoxy-D-gfycero-D-ga/flcro-nonulosonic acid) derivative (67), the stereoselectivity implying the operation of neighbouring group participation during the addition process (Scheme 10). °... 

When 1,6-allenynes were reacted with nucleophiles such as alcohols in the presence of Cp RuCl(cod) in methanol or in the presence of [Cp Ru(CH3CN)3] PFs in THF, functionalized 1,2-bisalkylidenecyclopentanes were produced via stereoselective addition of nucleophiles to ruthenacyclopentenes [107] [Eq. (46)]. This ruthenacycle obtained by oxidative coupling of the triple bond and the terminal double bond captures a proton from alcohol at the y-position of the metal affording a mono-carbene intermediate able to undergo a nucleophilic attack of alcohol. 

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