REACTION STUDY SHEET. NAME OF REACTION: Antarafacial (anti) Addition of an Electrophile (:E Nu:) to an Alkene

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1 REACTONSTUDYSEET NAMEOFREACTON: Antarafacial(anti)AdditionofanElectrophile(:E Nu:)toan Alkene mportantfeatureofthisreaction:theelectrophilicatomcarriesanon bondingpairofelectrons. Generalformofthereaction: Reactant Reagent Product(s) R 1 R 4 R 2 R 3 R 1 R 2 R 4 Aspecificexample Reactant Reagent Product(s) R 3 2 /Li/TF AcO Whatwayscanthisspecificexamplebeaskedonanexam(i.e.whatflashcardsdoneed?) 2 /Li/TF?? 2 /Li/TF AcO (±)? AcO Whatdoesthisreagentdo? t adds :E Nu: across a π bond of an alkene to give a bromohydrin. The addition is stereospecific to give the antarafacial(anti) adduct. This stereochemistry is a direct result of the involvement of a three membered cyclic onium ion intermediate, which is made possible by the lonepairontheelectrophilicatom.without this lone pair, the stereospecificity is lost because the three memberedcycliconiumionbecomesimpossibletoform.

2 Whatisthemechanismofthisreaction? R 1 R 4 R 2 R 3 R 1 R2 E R 4 R3 R 1 R 4 R 2 R 3 :Nu Whatisthestereochemistryofthisreaction?The addition is stereospecific. t occurs with antarafacial(anti)additionofthetwogroupstotheπbond(i.e.theelectrophilicatom,:e,the nucleophilicatom,nu:,areaddedtooppositefacesoftheπbond). Whatistheregiochemistryofthisreaction? The addition occurs with Markovnikov regiochemistry: the:e atom becomes bonded to the end of the π bond that is less able to carry a positivecharge(i.e.wouldmakethelessstablecarbocation),thenu:atombecomesbondedto theendoftheπbondthatisbetterabletosupportapositivecharge(i.e.wouldbethemorestable carbocation) sthereanintermediateinvolvedinthisreaction? There is a three membered cyclic onium ionintermediate.thisintermediatehaseveryatomwithacompleteouter shelloctet,whichmakes itlowerenergythanasimplecarbocation(stabilizedbyhyperconjugationorconjugationwithaπ bond),whichhasonecarbonatomthatiselectrondeficient(i.e.lacksacompleteoctet). Does this intermediate lead to any special reactivity or observations? Yes: this threemembered ring must open anti, so the overall addition is always antarafacial. When the double bond is part of a cyclohexene ring, the E Nu groups both end up axial, although the ring may then flip to make them both equatorial. Antarafacial addition will supersede the regiochemical preferenceformarkovnikovaddition. Whatreagentorcombinationsofreagentscanbeusedtomaketheactivereagentinthis reaction? AllreagentsareseparatedintotheE Nusegments. a.addingx O:X2/2O;2/K/2O;2/K/2O;NaO3/NaSO3/2SO4/2O;NaO/2O; g()2/2o/tf;etc. b.addingx OR:2/RO;g(OCOCF3)2/RO;etc. c.addingx OCOR[thisreactionisespeciallyusefulinanintramolecularversionbecauseit givescyclicesters,orlactones]:2/rco2li/tf;g()2/tf;g()2/eto;etc. d.adding N3:N3/C22 e.addingrs(e) X:PhS/C22;PhSe/C22;etc. f.addingx Y:2/Li/MeCN;/C22;etc. g.addingx NCO2R[thisreactionismostusefulintheintramolecularversion]: 2/ROCON2;g(OCOCF3)2/ROCON2;etc.

3 PracticeProblems: Whatisthemajororganicproductformedfromeachofthefollowingalkeneswiththe reagentspecified? (1)2/2O (2)g(OCOCF3)2/TF/MeO (3)C65Se/C22 (4)2/LiOCOC3/TF. (5)N3/C22 (6)C3S/C22 (a) (b) (c) (d) (e) (f) (g) (h) (i) (j) (k) (l) (m) (n) (o) (p) (q) (r) Whatalkenereagentcombinationshouldbeusedtoprepareeachofthefollowing additionproducts?[onlyoneenantiomerisshown,althoughsomeproductsmayberacemic] fmorethanonediastereoisomerorregioisomerwillbeformedasamajorproduct,givethe structureofthatotherproduct. (a) O (b) (c) O (d) (e) (f) go 2 CCF 3 (g) (h) O

4 (i) (j) g (k) S (l) O (m) AcOg (n) O (o) (p) O (q) (r) O SELECTEDANSWERS What is the major organic product formed from each of the following alkenes with the reagent specified? (s) O (t) MeO go 2 CCF 3 (b) The starting alkene is symmetrical not chiral; the product is racemic, but there is no regiochemistry involved in this addition. The antarafacial addition may result in addition of the electrophilic atom to the top face or the bottom face of the double bond with equal facility, but note how the two new chiral centers have stereochemistry that reflects the stereochemistry of the original double bond (Z). (1) (2) (3) (4) (5) (6) O MeO g OCOCF 3 SeC 6 5 SC 3 (f) The starting alkene is not symmetrical not chiral; the product is racemic, this addition will occur with Markovnikov regiochemistry. The antarafacial addition may result in addition of the electrophilic atom to the top face or the bottom face of the double bond with equal facility, but note how the two new chiral centers have stereochemistry that reflects the E stereochemistry of the original double bond. (1) (2) (3) go 2 CCF 3 O

5 (4) (5) (6) (i) The starting alkene is not symmetrical is chiral, the tert-butyl group prevernts the ring from inverting. Antarafacial addition in cyclohexanes forces the two new σ bonds to be formed in a trans-diaxial relationship. This supersedes the Markovnikov rule for regiochemistry of the addition. The upper product results from initial addition of the electrophilic atom to the top face of the π bond; the lower product results from initial addition of the electrophilic atom to the bottom face of the π bond. The products are regioisomers, but are both E isomers. The result of the reaction may be better understood seen in the chair projection formulas. (1) (2) (3) O gococf 3 O O gococf 3 gococf 3 O gococf 3 (4) (5) (6) What alkene reagent combination should be used to prepare each of the following addition products? [Only one enantiomer is shown, although some products may be racemic] R (a) The functional groups in this molecule are the bromine the hydroxy groups, which are on adjacent carbon atoms. This locates the O position of the double bond; these groups can be incorporated into a O R molecule by the antarafacial addition of O to an alkene through a three-membered cyclic bromonium ion intermediate. When we examine the Newman projection of this product, we see that when the bromine the hydroxy groups are anti to each other, so are the hydrogen atoms the alkyl groups. This means that in the starting alkene, the alkyl groups must be anti to each other, so must the hydrogen atoms. The starting alkene is therefore E-4-octene.

6 2 / 2 O (±) O R (b) The functional groups in this molecule are the iodine R R the azide groups, which are on adjacent carbon atoms. This locates the position of the double bond; these groups R can be incorporated into a molecule by the antarafacial addition of to an alkene through a three-membered cyclic iodonium ion intermediate. When we examine the Newman projection of this product, we see that when the iodine the azide group are syn to each other, so the first thing we must do is to re-write the Newman projection so that these two groups are anti to each other. n this conformation, the two alkyl groups are syn to each other, so are the hydrogen atoms. This means that in the starting alkene, the alkyl groups must be syn to each other, so must the hydrogen atoms. The starting alkene is therefore Z-4-octene. /C 2 2 (±) (f) The functional groups in this molecule are the methoxy group the mercury group, which are on adjacent carbon atoms. This locates the position of the double bond. They are both axial, which places them in an anti relationship; they can be go 2 CCF 3 incorporated into a molecule by the antarafacial addition of MeO gococf 3 to an alkene in methanol solvent through a three-membered cyclic mercurinium ion intermediate. The reagent itself is formed by using mervury () trifluoroacetate in methanol. g(ococf 3 ) 2 /MeO go 2 CCF 3 AcOg Ph (m) The functional groups in this molecule are the acetate the g mercuriacetate groups, which are on adjacent carbon atoms. This AcO locates the position of the double bond; these groups can be R incorporated into a molecule by the antarafacial addition of AcOg to an alkene through a three-membered cyclic mercurinium ion intermediate. The mercury atom is attached to a secondary carbon, the acetate is secondary benzylic, which corresponds to Markovnikov regiochemistry in the addition. When we examine the Newman projection of this product, we see that the bromine sulfur atoms are anti to each other, as are the two alkyl groups the two hydrogen atoms. This means that in the starting alkene, the alkyl groups must be anti to each other, so must the hydrogen atoms. The starting alkene is therefore the E isomer. The other chiral center present in the product is not affected during the reaction, so it must have been present already in the starting alkene. g() 2 /TF AcOg AcOg