The Halogen–Samarium Exchange Reaction: Synthetic Applications and Kinetics

Abstract

Fast I/Sm and Br/Sm exchanges take place when various aromatic or heterocyclic iodides and bromides are treated with nBu 2 SmCl·4 LiCl and nBu 3 Sm·5 LiCl, respectively.The resulting organosamarium reagents were efficiently quenched with aldehydes,k etones,a nd imines.A lso,t hey undergo acylations when treated with N,N-dimethylamides leading to ketones.The rate of the Br/Sm exchange for atypical aryl bromide was determined and found to be 8.5 10 5 faster than the Br/Mg exchange,i ndicating that the rate of am etalexchange is related to the ionic character of the carbon-metal bond and to the metal electronegativity.Organometallics are key nucleophilic reagents for organic synthesis, [1] and their efficient preparation is an important synthetic task. Besides the oxidative addition [2] of am etal to an organic halide,the halogen-metal exchange reaction [3][4][5] is one of the most important synthetic routes to aryl and heteroaryl organometallics.T he halogen/lithium exchange [3] is certainly the most used in synthesis;h owever,t he functional group tolerance of aryllithiums is rather moderate. [4] As an alternative,the halogen/magnesium exchange [5] is compatible with large number of functional groups;nevertheless,this exchange reaction is considerably slower than the halogen/ lithium exchange. [6] Further,t he iodine/zinc exchange proceeds at an even slower rate. [7] Besides ate-metal reagents such as manganates [8] and cuprates [9] undergo an exchange, but the atom economy [10] of these reactions is moderate.Recently,w eh ave reported an ew halogen/lanthanum exchange reaction and have found that this exchange is at least 10 6 faster than the halogen/magnesium exchange.A lso, the I/La or Br/La exchange displays better functional group tolerance than the halogen/lithium exchange. [11] This led us to postulate that the rate of the halogen/metal exchange depends on the ionic character of the carbon-metal bond of the exchange reagent, and that the functional group compat-ibility also depends on this ionic character and therefore on the electronegativity [12] of the metal (Scheme 1).Forp roving this relation, we turned our attention to samarium which has an electronegativity of 1.17 compared to 1.10 for lanthanum. We therefore predicted that the halogen/ samarium exchange should be slower than the halogen/ lithium, the halogen/lanthanum, and the halogen/cerium exchanges,a nd that the functional group tolerance of the resulting arylsamarium(III) reagent should be better than that of the corresponding lanthanum(III) reagents.Moreover, organosamarium reagents already proved their utility as nucleophiles,b ut only few preparation methods of these organometallics have been reported. [13] Ah alogen/samarium exchange will then provide an ew access to these reagents.Herein, we report the preparation of halogen/samarium exchange reagents and their use for performing efficient I/Sm and Br/Sm exchanges.W edescribe also the reaction of these new aryl-and heteroarylsamarium reagents with various electrophiles and provide an appr...

Preparation of Polyfunctional Biaryl Derivatives by Cyclolanthanation of 2‐Bromobiaryls and Heterocyclic Analogues Using nBu2LaCl⋅4 LiCl

“…As shown in Table , neither the lithiation nor magnesiation of 2 a led to any cyclometalated product (entries 1 and 2). Br/Sm exchange provided the cyclometalated intermediate in only moderate yields, as shown by the iodolysis leading to 2,2′‐diiodobiphenyl ( 4 a ) in only 31–40 % yield (entries 3 and 4). However, the use of n Bu 2 LaCl⋅4 LiCl gave satisfactory results.…”

Herstellung von polyfunktionellen Biarylderivaten durch Cyclolanthanierung von 2‐Bromobiarylen und heterocyclischen Analoga unter Verwendung von nBu2LaCl⋅4 LiCl

“…Wie in Tabelle gezeigt, haben sowohl Lithiierungen als auch Magnesierungen von 2 a nicht zum cylometallierten Produkt geführt (Einträge 1 und 2). Nach Durchführung eines Br/Sm‐Austausches wurde das cyclometallierte Intermediat in moderaten Ausbeuten erhalten, gezeigt an Iodolysereaktionen, die zu 2,2′‐Diiodobiphenyl ( 4 a ) in nur 31–40 % Ausbeute führten (Einträge 3 und 4). Mit n Bu 2 LaCl⋅4 LiCl jedoch wurden zufriedenstellende Ergebnisse erzielt.…”

Preparation and reactions of polyfunctional magnesium and zinc organometallics in organic synthesis

“…This hypothesis led to the discovery of halogen/lanthanide exchange reactions. 14 The replacement of LiCl in the turbo-Grignard reagent ( 9 ) with lithium alkoxides (LiOR) led to even more powerful exchange reagents ( s BuMgOR 1 ·LiOR 1 and s Bu 2 Mg·2LiOR 1 ; R 1 = 2-ethylhexyl) soluble in toluene. These reagents allowed the performance of some Cl/Mg-exchanges 15 as well as regioselective exchanges on various dibromopyridines such as 10 .…”