Stereospecific 1,2‐Migrations of Boronate Complexes Induced by Electrophiles

Abstract The stereospecific 1,2‐migration of boronate complexes is one of the most representative reactions in boron chemistry. This process has been used extensively to develop powerful methods for asymmetric synthesis, with applications spanning from pharmaceuticals to natural products. Typically, 1,2‐migration of boronate complexes is driven by displacement of an α‐leaving group, oxidation of an α‐boryl radical, or electrophilic activation of an alkenyl boronate complex. The aim of this article is to summarize the recent advances in the rapidly expanding field of electrophile‐induced stereospecific 1,2‐migration of groups from boron to sp2 and sp3 carbon centers. It will be shown that three different conceptual approaches can be utilized to enable the 1,2‐migration of boronate complexes: stereospecific Zweifel‐type reactions, catalytic conjunctive coupling reactions, and transition metal‐free sp2–sp3 couplings. A discussion of the reaction scope, mechanistic insights, and synthetic applications of the work described is also presented.


Introduction
Chiral boronic acids and related derivatives are valuable building blocks in modern synthesis as they can be easily prepared with high levels of enantioselectivity. [1] Crucial to the synthetic utility of organoboron compounds is their ability to be transformed stereospecifically into arange of functional groups. [2] In general terms,these transformations are initiated by the addition of anucleophile to the boron atom, resulting in boronate complex formation, followed by as tereospecific 1,2-migration of am etal migrating group to the adjacent carbon centre. [3] An example of such ap rocess is the homologation of boronic esters with carbenoids (Scheme 1a), which has seen wide application in asymmetric synthesis.I n this context, Mattesonss ubstrate-controlled homologation [4] and Aggarwalsr eagent-controlled lithiation-borylation [5] methodologies are particularly noteworthy.R ecently,t he fields of radical chemistry with stereospecific 1,2-migration has been shown that radicals next to boronates can be generated by the addition of carbon-centred radicals to alkenyl boronates [6] or by a-C(sp 3 ) À Habstraction. [7] These aboryl radical anions can then undergo single-electron oxidation followed by 1,2-migration to afford the desired products. This active field has been recently reviewed so will not be discussed further here. [8] Stereospecific 1,2-migrations of alkenyl or aryl boronates can be induced by reactions with suitable electrophiles (Scheme 1c). Although significant and substantial work in this field has been reported, systematic review articles are rare. [9] Therefore,the aim of this Minireview is to provide an overview of recent developments in electrophile-induced stereospecific 1,2-migration of boronate complexes,including Zweifel-type reactions,conjunctive cross-couplings,and transition metal-free sp 2 -sp 3 couplings.T he scope of this review also extends to boronate complexes containing strained sbonds,which exhibit similar reactivity to p-bonds. In 1967, Zweifel first reported the stereoselective synthesis of alkenes using organoboron intermediates (Scheme 2a). [10] Ther eaction was initiated by hydroboration of alkyne 1 with dicyclohexylborane,r esulting in the formation of alkenyl borane 2a,which was then reacted with iodine in the presence of sodium hydroxide, leading to Z-alkene 5.T he reaction proceeds via cyclic iodonium ion intermediate 3,followed by astereospecific 1,2-migration affording b-iodoborinic acid 4.This species then undergoes anti elimination in the presence of base, which results in an overall inversion of alkene geometry from 2 to 5.Furthermore,itwas later proved that the migrating moiety underwent 1,2-migration with complete retention of configuration by employing diastereomerically pure borane 6 as as ubstrate in the reaction (Scheme 2b). [11] Considering the stereochemical features of this process,asyn elimination (giving the E-alkene) should be possible if the interaction between the b-halogen and boron of the b-haloboron intermediate could be enhanced. Indeed, Zweifel demonstrated that syn elimination was favoured if astrong electron-withdrawing group (CN) was introduced on boron, which allowed coordination of the bromide to boron in intermediate 10 and resulted in the formation of E-olefins 11 (Scheme 2c). [12] Thev inyl group is an important functional group, commonly found in natural products and functional materials. [13] In this context, the Zweifel olefination provides an excellent method to convert aboronic ester into avinyl group by employing vinyl lithium or the corresponding Grignard reagent. [14] In 2009, Aggarwal applied this concept to the total synthesis of (+ +)-faranal (Scheme 3). [15] Enantioenriched boronic ester 12 was reacted with vinyl lithium and then treated with iodine and sodium methoxide,w hich provided alkene intermediate 13.Without isolation of 13,insitu hydroboration and oxidation gave alcohol 14 in 69 %yield and with excellent The stereospecific 1,2-migration of boronate complexes is one of the most representative reactions in boron chemistry.T his process has been used extensively to develop powerful methods for asymmetric synthesis,with applications spanning from pharmaceuticals to natural products.T ypically,1,2-migration of boronate complexes is driven by displacement of an a-leaving group,oxidation of an a-boryl radical, or electrophilic activation of an alkenyl boronate complex. The aim of this article is to summarize the recent advances in the rapidly expanding field of electrophile-induced stereospecific 1,2-migration of groups from boron to sp 2 and sp 3 carbon centers.Itwill be shown that three different conceptual approaches can be utilized to enable the 1,2migration of boronate complexes:stereospecific Zweifel-type reactions,c atalytic conjunctive coupling reactions,and transition metalfree sp 2 -sp 3 couplings.Adiscussion of the reaction scope,mechanistic insights,a nd synthetic applications of the work described is also presented.
diasteroselectivity.F inally,( + +)-faranal was obtained by oxidation of 14 with pyridinium chlorochromate (PCC). Additionally,t his strategy was also successfully used by Morken to introduce an isoprenyl group in the total synthesis of debromohamigeran E( Scheme 4). [16] Alkene 16 was formed in high yield on ag ram-scale by Zweifel olefination of boronic ester 15 with isopropenyllithium.
Enantioenriched tertiary boronic esters 17 have also been subjected to the same Zweifel olefination conditions to form vinyl-substituted quaternary stereogenic centers 18 with complete enantiospecificity (Scheme 5a). [17] It is noteworthy that allylsilanes 20 could also be obtained in high enantiomeric excess using this protocol (Scheme 5b). [18] However, the preparation of vinyllithium typically relies on in situ lithium-tin exchange of tetravinyltin, or lithium-bromide exchange of vinyl bromide,w hich reduces its practicality. Therefore,vinyl Grignard reagents,which are easier to handle and commercially available,h ave also been explored in the Zweifel olefination (Scheme 5c). [19] Aconsequence of changing from vinyllithium to vinyl Grignard reagents,i st hat magnesium pinacolate is readily formed from Mg II salts and the pinacol ligand on boron. Therefore,u pon reaction of ab oronic ester with av inyl Grignard reagent, trivinyl boronate species 21 is formed instead of the mono-vinyl pinacolato boronate.Normally,this necessitates the use of an excess of vinyl Grignard (4.0 equivalents) but by screening various reaction conditions,i tw as found that using am ixed solvent system (1:1 THF/DMSO) allowed boronic esters to undergo vinylation using 1.2 equivalents of vinyl Grignard. [20] Whilst this method shows synthetic utility,itisnot suitable for sterically hindered tertiary boronic esters,w hich makes the higher reactivity of vinyllithium more attractive.T his is illustrated in af ive-step synthesis of (AE)-grandisol, where aZ weifel olefination was used to convert tertiary boronic ester 24 into terminal alkene 25 (Scheme 5d). Subsequent hydroboration/oxidation and Cope elimination provided the natural product in good yield and high diastereoselectivity. [21] In the past decade,t he scope of the Zweifel olefination reaction has been greatly expanded. Fore xample, a-heteroatom-substituted alkenyl metals 27 have been successfully coupled with secondary boronic esters (Scheme 6a), [20] which provides great opportunities for application in synthesis as the vinyl ether products 29 can be easily converted into ketones by hydrolysis under mild conditions. [19] This methodology was used to convert boronic ester 30 into enol ethers 31 and 32 in the synthesis of the reported and revised structures of baulamycins Aa nd B, respectively (Scheme 6b). [22] Theenantiospecific alkynylation of secondary and tertiary boronic esters is an extension to the established Zweifel olefination. In situ a-lithiation of vinyl bromides or carbamates in the presence of the boronic ester provided boronate complexes 33 that underwent iodine-induced olefination to give alkenyl bromides or carbamates 34 (Scheme 7a). [23] Scheme 2. Zweifel olefination:selective synthesis of olefins.

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Subsequent base-induced 1,2-elimination afforded the alkynylated products 35.I nt his reaction, various terminal and silyl-protected alkynes can be obtained with high enantiospecificity,a nd ab road range of functional groups (alkenes, azide,alkyne,and ester groups) are tolerated. Furthermore,it was used in the total synthesis of tatanan A, where complex boronic ester 36-constructed using iterative reagent-controlled homologation-was employed in an enantiospecific Zweifel-type alkynylation to afford alkyne 37 (Scheme 7b). [24] It should be noted that alkynyl anions cannot be used directly in Zweifel-type alkynylation since they react reversibly with boronic esters.H owever,t hey can used in reactions with boranes or borinic esters. [25] Intramolecular Zweifel olefination has also been achieved, which provides access to methylene cycloalkanes (Scheme 8). [26] Alkenyl bromide-containing boronic ester 39-obtained with high stereoselectivity from 38 by lithiation-borylation-was treated with t BuLi to form an alkenyl lithium intermediate through lithium-halogen exchange.T his species cyclised to give an intermediate cyclic boronate complex. Subsequent treatment with iodine and methanol under Zweifel olefination conditions afforded ring contracted methylene cyclopentane 40 in 97 %y ield with 100 %e nantiospecificity,w hich was then transformed into the natural product (À)-filiformin. This ring contraction methodology was extended to the more challenging synthesis of highly strained methylene cyclobutane 41,w hich was obtained in 63 %y ield and > 99:1 e.r.
Since its introduction over 50 years ago,t he Zweifel olefination has become ap owerful method to transform boronic esters into structurally diverse alkenes with excellent control of alkene geometry.I mportantly,b yp roceeding through as tereospecific 1,2-migration mechanism, the chiral information of the boronic ester substrate is fully translated to the alkene product. This high level of stereocontrol is often unachievable with metal-catalyzed Suzuki-Miyaura crosscouplings,which has resulted in the Zweifel olefination being commonly employed in the synthesis of complex natural products and pharmaceutical intermediates.

Sulfur and Selenium-Based Electrophiles
In 2017, Aggarwal reported am odified Zweifel-type olefination proceeding through an ovel syn elimination process (Scheme 9). [27] This was achieved by employing PhSeCl as the electrophile for the selenation of alkenyl boronates 43,which led to b-selenoboronic esters 46 through the stereospecific 1,2-migration ring-opening of seleniranium intermediates 45.I tw as found that m-CPBAw as able to chemoselectively oxidise the selenide to give selenoxide intermediate 47,which underwent syn elimination to provide

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Chemie alkenes 44 in high stereoselectivity.DFT calculations showed that the oxygen atom of selenoxide 47 interacts strongly with the boron atom, therefore resulting in a syn elimination pathway.T his selenium-mediated olefination showed broad substrate scope in terms of both the boronic esters and the alkenyl lithium reagents (di-and trisubstituted), leading to synthetically useful alkene products 44 with high selectivity for retention of olefin geometry.

Transition Metal-Catalyzed Conjunctive Cross-Couplings
It is known that p-acidic late transition metal complexes in high oxidation states,s uch as Pd II and Ni II ,a re highly electrophilic and able to strongly coordinate to p-bonds.I n 2015, Morken reported that such species could interact with the electron-rich p-bond of alkenyl boronate complexes, triggering a1 ,2-migration of an alkyl or aryl group on boron (Scheme 11). [29] Key to the success of this reaction was the use of aryl triflates rather than aryl halides,w hich generated amore reactive cationic Pd II intermediate,and the use of the Mandyphos ligand L 2 to reduce the propensity for b-hydride elimination of intermediate alkylpalladium(II) intermediates. Furthermore,u sing ac hiral phosphine ligand gave the conjunctive coupling products in good yield and high enantioselectivity.T he choice of diol ligand on boron played an important role in determining the enantioselectivity. Interestingly,t he optimum diol ligand was found to be dependent on the triflate electrophile,w ith neopentyl glycol Morken has built on this discovery with an umber of important developments (Scheme 13). Firstly,t he reaction has been extended to Grignard reagents instead of organolithiums and to halide electrophiles in place of triflates (Scheme 13 a). [30] It was found that the conjunctive crosscoupling was inhibited by halide ions,w hich had previously limited the use of aryl halide electrophiles.H owever,t his limitation was overcome by using ac ombination of NaOTf and DMSO as additives,w hich allowed the formation of cross-coupled products 61 with high yields and enantioselec-tivities.T he effect of these additives was two-fold:( i) the NaOTfresulted in precipitation of the sodium halide salt, thus avoiding the detrimental coordination of halide ions to palladium and creating the more electrophilic Pd II complex; and (ii)the combination of NaOTf and DMSO greatly increased the stability of the alkenyl boronate complexes 60 generated from the vinyl Grignard reagent. Conjunctive cross-couplings between alkenyl boronic esters 62,v inyllithium, and aryl/alkenyl triflate were next explored (Scheme 13 b). [31] These reactions proceed through bis-alkenylboronate complexes 63,w ith the Pd II intermediate showing apreference for reaction with the less substituted alkene,and allow access to chiral allylboronic esters 64.Extension of this approach to boronate complexes derived from a-substituted alkenyl boronic esters 65 allowed access to highly desirable tertiary boronic esters 66 with good enantioselectivity (Scheme 13 c). [32] b-Substituted alkenyl boronic esters 67 were also successfully employed, but required alterations to the boron ligand design to prevent undesired Suzuki-Miyura-type reactivity,w hich was found to dominate with pinacol and neopentyl glycol boronic ester substrates (Scheme 13 d). [33] A more sterically demanding boronic substituent (mac), derived from acenaphthoquinone,w as required to minimize Suzuki-Miyaura coupling and direct the approach of the palladium-(II) complex to the more congested b-carbon, thus enabling access to the conjunctive cross-coupling products 68 with excellent stereoselectivities.F urthermore,t his approach was applied to b-silyl alkenyl boronate complexes 69 for the efficient construction of anti-1,2-borosilanes (Scheme 13 d). [34] Finally,u sing propargylic carbonates 72 in place of aryl triflates furnished fully substituted b-boryl allenes with high enantioselectivity (Scheme 13 e). [35] It was found that amethanol additive resulted in formation of ad imethoxyboronate intermediate through boron ligand exchange,w hich significantly enhanced both the yield and enantioselectivity of the reaction.
Morken has since extended this conjunctive cross-coupling to include enyne-derived boronate complexes 74,which give a-hydroxy allenes 75 after oxidative work-up (Scheme 14). [36] Interestingly,e nyne boronates derived from Z-alkenes provided a-boryl allenes with high diastereoselectivity,w hereas E-alkene substrates gave low diastereoselectivity.T his was rationalized based on the steric interactions between the migrating group and the palladium complex:i n the case of the Z-alkene,complex syn-76 has these moieties in close proximity so they orientate to minimize steric interactions,m aking anti-76 the reactive conformer;w hereas in the E substrate,t here is little interaction between the migrating group and the palladium complex in either conformers anti-77 or syn-77,r esulting in poor diastereocontrol. Forreactions with alkyl migrating groups,substitution of the pinacol ligand on boron for an acenaphthoquinone-derived boronic substituent (hac*) was essential for achieving high stereoselectivity,w hich was attributed to enhanced catalystsubstrate steric interactions.

Minireviews
showed that these reactions could be extended to boronic esters and rendered asymmetric using Pd(BINAP) catalysts (Scheme 15). [38] Thei ndole-derived boronate complexes 78 reacted with Pd(p-allyl) complexes,t of orm indolin-2-yl boronic esters 79 with high levels of diastereo-, regio-, and enantioselectivity.T he boronic esters products were oxidized with basic hydrogen peroxide to provide the corresponding indoles 80.Alternately,protodeborylation of benzylic boronic ester products (79,R 1 = aryl) with TBAF trihydrate gave 2,3disubsituted indolines 81.V arious aryl and alkyl migrating groups could be employed in this asymmetric three-component coupling,w hich provided indoline products with three contiguous stereogenic centers.The scope of the reaction was subsequently extended to 3-alkyl-substituted indoles by using aP d/phosphoramidite catalyst system, which enabled the enantioselective formation of indolin-2-yl boronic esters 82 with adjacent quaternary stereocenters. [39] Morken has also demonstrated that nickel(II) complexes interact with alkenyl boronates in as imilar manner to palladium(II) complexes. [40] When investigating ao ne-pot 9-BBN hydroboration/enantioselective conjunctive cross-coupling reaction between alkenes and aryl iodides,t hey found that the Pd/Mandyphos catalyst system that was optimal for pinacol boronate substrates only provided racemic products when applied to the 9-BBN-derived boronates 83 (Scheme 16). However, anickel catalyst in combination with the diamine ligand (S,S)-L 3 gave the products 84 in high enantioselectivity.Detailed mechanistic studies indicated that the reaction involves initial oxidative addition of the aryl iodide to Ni 0 to give aN i II species,w hich binds the alkene (forming 85)t oi nduce 1,2-migration with stereospecific anti addition of the migrating group and Ni II across the alkene. Morken subsequently extended the scope of these nickelcatalyzed conjunctive cross-couplings to other electrophiles, including alkyl halides and acid chlorides. [41] Scheme 13. Catalytic conjunctive cross-coupling reactions enabledb ypalladium-induced 1,2-migration.R M = Migratinggroup.

Stereospecific sp 2 -sp 3 Coupling of Chiral Boronic Esters with Aromatic Compounds
In 2014, Aggarwal disclosed an efficient and general method for stereospecific sp 2 -sp 3 couplings of electron-rich (hetero)aromatics with chiral secondary and tertiary boronic esters (Scheme 17 a). [42] Thereaction occurs by initial reaction of an aryllithium with boronic ester 18 to form aryl boronate complex 86,f ollowed by treatment with an electrophilic halogenating agent to provide the arylated product 87 in high yield and with complete stereospecificity.T his process could be used to introduce various electron-rich aromatic groups, including 5-membered ring heteroaromatics and 6-membered ring aromatics with meta-electron-donating groups,a nd was applicable to abroad range of secondary and tertiary boronic esters with different steric demands.I nm ost cases,N BS was the optimal electrophile,w ith NIS being employed in cases where further halogenation of the electron-rich aromatic ring occurred. Mechanistically,t he addition of NBS to the aromatic ring of boronate complex 86 generates cation 88. This triggers as tereospecific 1,2-migration, forming d-halo allylic boronic ester intermediate 89,a nd subsequent elimination/rearomatization leads to the arylated product 87. Subsequent DFT calculations on the reaction between furyl boronate complex 86 a and NBS provided evidence for simultaneous electrophilic bromination and 1,2-migration steps,without formation of the postulated cationic intermediate 88. [43] In later studies,i tw as found that the coupling of 6membered ring aromatics was dramatically affected by solvent choice (Scheme 17 b). [43] Solvent exchange from THF to MeOH led to improved yields of coupled products 87,which was due to areduction of the amount of undesired S E 2b romination of the CÀBb ond of 86.I nterestingly, switching to less nucleophilic alcohol solvents promoted an alternative arylation pathway to provide Bpin-incorporated coupling products 93 with complete stereospecificity.U sing an i PrOH-MeCN mixed solvent system resulted in an inefficient nucleophile-promoted Bpin elimination of dearomatized intermediate 91,t herefore 91 underwent a1 ,2-Wagner-Meerwein shift [44] of the Bpin moiety to form carbocation 92,w hich relieved steric encumbrance and allowed subsequent rearomatization by deprotonation to afford 93.
Aggarwal has since expanded this concept of electrophilic-induced arylation of boronic esters to allow coupling of ar ange of substituted aromatic rings.F or example,p henyl- acetylene products 95 and 96 could be accessed by coupling between p-lithiated phenylacetylenes (generated by halogenlithium exchange of the corresponding bromide 94)a nd arange of chiral boronic esters 18 (Scheme 18). [45] Treatment of the intermediate TMS-phenylacetylene-derived boronate complex with NBS results in bromination of the alkyne motif, which triggered as tereospecific 1,2-migration leading to dearomatized bromoallene intermediate 97.U sing unhindered neopentyl glycol boronic esters and MeOH as solvent, subsequent nucleophile-promoted elimination and rearomatization of 97 a occurred, resulting in the formation of coupled product 95.Incontrast, the use of the more hindered pinacol boronic esters and i PrOH as the solvent prevented nucleophile-promoted elimination, therefore 1,2-Wagner-Meerwein shift of the Bpin moiety occurred instead. This led to carbocation 98,w hich, after loss of ap roton, furnished the ortho Bpin-incorporated product 96.
Asimilar strategy was used by Aggarwal to access aniline products 110 through N-acylation of boronate complexes generated from lithiated para-a nd ortho-phenyl hydrazines 108 (Scheme 20 a). [47] Acylation of the para-hydrazinyl boronate complex with trifluoroacetic anhydride (TFAA) formed acyl ammonium 109,w ith subsequent concurrent 1,2-migration and N À Nb ond cleavage.A fter Bpin elimation/rearomatization and further reaction of the resulting amino group with TFAA, the trifluoroacetamide products 110 were isolated in good yield and with complete stereospecificity. Fort he corresponding ortho-hydrazinyl boronate complexes, changing the N-activator from TFAA to the less reactive 2,2,2-trichloro-1,1-dimethylethyl chloroformate (Me 2 Troc-Cl) was required to obtain the ortho-aniline products in good yield.

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Chemie suprafacial Lewis acid mediated 1,3-borotropic shift of 113 gave enantioenriched ortho-substituted benzylic boronic esters 114 in high yields and stereospecificities.Furthermore, through the use of enantioenriched secondary benzylic amine substrates,itwas shown that the anti-S N 2' and 1,3-borotropic shift processes also proceeded with high stereospecificity, which allowed doubly stereospecific reactions to occur when enantioenriched boronic esters were also employed (see product 114 c). Further work highlighted the synthetic utility of the intermediate enantioenriched dearomatized tertiary boronic esters 113,w hich were utilized in rearomatizing allylic Suzuki-Miyaura cross-coupling reactions to provide complex enantioenriched 1,1-diarylmethane products 116 with three readily addressable points of diversification (Scheme 20 c). [49] In an alternative N-acylation-induced 1,2-migration of aryl boronate complexes,A ggarwal developed ag eneral protocol for the stereospecific coupling of chiral secondary and tertiary boronic esters with electron-deficient N-heteroaromatics (Scheme 21 a). [50] After formation of chiral boronate complexes 119 from lithiated 6-membered ring Nheterocycles 117 (including pyridines,q uinolines and isoquinolines), 1,2-migration was triggered by N-acylation with 2,2,2-trichloroethyl chloroformate (Troc-Cl), leading to dearomatized tertiary boronic ester 121 via the intermediate Nacyl pyridinium 120.Aone-pot oxidation/hydrolysis/elimination sequence finally furnished the coupled heteroaromatic products 118 with complete stereospecificity.Amodified approach was reported by Ready,i nw hich the pyridyl boronate complexes 119 were generated by adding organometallic reagents to 4-pyridyl boronic ester 18 e (Scheme 21 b). [51] It was shown that, in addition to organolithium reagents,o rganozinc and Grignard reagents could also be employed in this heteroarylation reaction.

Electrophile-Induced 1,2-Migration of Strained Boronates
It is shown above that electrophilic metal complexes, including Pd II and Ni II ,c an coordinate with the p-bonds of alkenyl boronate complexes to trigger 1,2-migration and achieve carbometallation of alkenes (Scheme 11). Although such metal species readily react with CÀC p-bonds,t hey generally do not react with CÀC s-bonds.However,Aggarwal has recently reported that cationic palladium(II) complexes can activate s-bonds of highly strained boronate complexes to promote 1,2-migration and achieve s-bond carbopalladations (Scheme 22). [52] To achieve such aprocess,bicyclo[1.

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Chemie central s-bond, and the release of this strain provides significant driving force to allow efficient reaction of 124 with aP d II catalyst. This enabled ad istal cross-coupling of boronic esters and aryl triflates to provide 1,1,3-trisubstituted cyclobutanes 125 in high yields and with complete stereospecificity and diastereocontrol. Thep roposed mechanism involves initial oxidative addition of the aryl triflate to the Pd 0 catalyst 126 to form the cationic Pd II complex 127.Reaction of 127 with boronate complex 124 occurs at the more nucleo-philic b-carbon to provide the cyclobutyl palladium intermediate 128.A s1 ,2-migration requires an anti-periplanar alignment of the migrating group (R M )and the breaking C À C bond, this makes the endo face of the reactive conformer more sterically hindered, thus the bulky metal complex approaches from the more exposed exo face.T his forms intermediate 129 with complete diastereocontrol for syncarbopalladation, which, after stereospecific reductive elimination provides 125 in excellent diastereoselectivity.T his interesting strain release-driven 1,2-migation of bicyclo-[1.1.0]butyl boronate complexes opens up new directions for stereospecific transformations involving 1,2-migration to sp 3hybridized carbons.

Summary and Outlook
Organoboron compounds are indispensable in synthetic chemistry,p roviding ap owerful platform for myriad transformations.T he stereospecific 1,2-migration of boronate complexes is one of the most important processes in this area. This can be triggered by as uitable a-leaving group, oxidation of a-boryl radicals,o re lectrophilic activation. As described above,e lectrophilic activation of boronate complexes can take many different forms and provide access to ad iverse array of products from readily available chiral Scheme 20. Coupling boronic esters with lithiated arylhydrazines and ortho-lithiated benzylamines. TFA = trifluoroacetyl. DMT = 2,2,2-trichloro-1,1-dimethylethoxycarbonyl.

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Chemie boronic ester.Inthe case of the Zweifel olefination, reaction of alkenyl boronate complexes with iodine transforms boronic esters into alkenes with high selectivity for inversion of alkene geometry,p roviding av aluable methodology that has been exploited extensively in total synthesis.This concept has more recently been extended chalcogenation of alkenyl boronate complexes,i ncluding selenation, which provides au nique opportunity to switch the stereoselectivity of the Zweifel olefination from inversion to retention. Furthermore, the principles behind the Zweifel olefination have inspired the development of ab road range of arylation and heteroarylation reactions.A ni mportant advance in alkenyl boronate complex reactivity has been the development of enantioselective metal-catalyzed conjunctive cross-couplings, which have greatly expanded the range of electrophiles that can be employed in electrophile-induced 1,2-migration chemistry.T his new area in boron chemistry and has since been extended to boronate complexes containing highly strained s-bonds in place of p-bonds,p roviding further unique opportunities for reaction development.
Future developments could see the application of boronic esters in stereospecific 1,2-migrations of alkynyl boronate complexes,w hich have so far been unsuccessful due to their instability.I na ddition, the development of new electrophilic triggers for various boronate complexes will extend the scope of the chemistry,leading to new opportunities in asymmetric synthesis.W hile the field of electrophile-induced 1,2-migra-tion of boronate complexes is over 50 years old, it remains an exciting area that is continually expanding.I ti sr emarkable that the seminal olefination work by Zweifel in 1967 has inspired so many new methodologies with broad-ranging applications in synthetic chemistry.