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Ei-ichi Negishi - One of the best experts on this subject based on the ideXlab platform.
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Arylethyne Bromoboration–Negishi Coupling Route to E- or Z-Aryl-Substituted Trisubstituted Alkenes of ≥98% Isomeric Purity. New Horizon in the Highly Selective Synthesis of Trisubstituted Alkenes
Advanced synthesis & catalysis, 2010Co-Authors: Chao Wang, Tomas Tobrman, Ei-ichi NegishiAbstract:Despite major advances in the syntheses of strictly (≥98%) regio- and stereodefined alkenes via “elementometalation”[1]–Pd- or Ni-catalyzed cross-Coupling developed since 1976,[2]-[4] efficient and highly (≥98%) selective syntheses of tri- and tetrasubstituted alkenes continue to provide major synthetic challenges. The Zr-catalyzed alkyne carboalumination–Negishi Coupling[3][4] (Eq. 1 in Scheme 1) has provided a highly selective and widely used method for the synthesis of trisubstituted alkenes.[4b] Although this method is broad in synthetic scope with respect to R1 of the starting alkyne (R1C≡CH), the R2 group of the organoalanes to be added to R1C≡CH has been practically limited to Me, and a limited number of alkyl groups including allyl and benzyl groups.[3–6] On the other hand, in an alkyne bromoboration–Negishi-Suzuki tandem cross-Coupling process (Eq. 2 in Scheme 1) reported by Suzuki in 1988,[7] bromoboration of R1C≡CH is followed by incorporation of both R2 and R3 groups by Pd-catalyzed cross-Coupling reactions of wide synthetic scopes, thereby promising to provide a method of very wide applicability for synthesizing trisubstituted alkenes. In reality, however, all reported examples[7] of Eq. 2 in Scheme 1 and of its modification involving double Negishi Coupling reactions[8,9] (Eq. 3 in Scheme 1) involve the use of only alkylethynes, even though haloboration of aryl- and alkenyl-substituted ethynes are known to proceed well.[10] Scheme 1 Highly (≥98%) selective “elementometalation” –Pd-catalyzed cross-Coupling routes to trisubstituted alkenes. As readily suspected, competitive debromoboration of 2 to revert to the starting alkynes would be the main cause of difficulty in the Pd-catalyzed cross-Coupling of 2, and the fact that those derived from aryl- and alkenyl-substituted ethynes are benzylic and allylic bromides, respectively, besides being alkenyl bromides must undoubtedly be responsible for their significantly higher propensity to undergoing debromoboration, as compared with that of alkylethyne-derived 2. Thus, for example, the reaction of 2a, generated by bromoboration of phenylethyne followed by treatment with pinacol, with (E)-1-octenylzinc bromide in the presence of Pd(DPEphos)Cl2 (0.5 mol %) at 23 °C for 2 h led to the formation of the desired 3a in
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arylethyne bromoboration Negishi Coupling route to e or z aryl substituted trisubstituted alkenes of 98 isomeric purity new horizon in the highly selective synthesis of trisubstituted alkenes
Advanced Synthesis & Catalysis, 2010Co-Authors: Chao Wang, Tomas Tobrman, Ei-ichi NegishiAbstract:Despite major advances in the syntheses of strictly (≥98%) regio- and stereodefined alkenes via “elementometalation”[1]–Pd- or Ni-catalyzed cross-Coupling developed since 1976,[2]-[4] efficient and highly (≥98%) selective syntheses of tri- and tetrasubstituted alkenes continue to provide major synthetic challenges. The Zr-catalyzed alkyne carboalumination–Negishi Coupling[3][4] (Eq. 1 in Scheme 1) has provided a highly selective and widely used method for the synthesis of trisubstituted alkenes.[4b] Although this method is broad in synthetic scope with respect to R1 of the starting alkyne (R1C≡CH), the R2 group of the organoalanes to be added to R1C≡CH has been practically limited to Me, and a limited number of alkyl groups including allyl and benzyl groups.[3–6] On the other hand, in an alkyne bromoboration–Negishi-Suzuki tandem cross-Coupling process (Eq. 2 in Scheme 1) reported by Suzuki in 1988,[7] bromoboration of R1C≡CH is followed by incorporation of both R2 and R3 groups by Pd-catalyzed cross-Coupling reactions of wide synthetic scopes, thereby promising to provide a method of very wide applicability for synthesizing trisubstituted alkenes. In reality, however, all reported examples[7] of Eq. 2 in Scheme 1 and of its modification involving double Negishi Coupling reactions[8,9] (Eq. 3 in Scheme 1) involve the use of only alkylethynes, even though haloboration of aryl- and alkenyl-substituted ethynes are known to proceed well.[10] Scheme 1 Highly (≥98%) selective “elementometalation” –Pd-catalyzed cross-Coupling routes to trisubstituted alkenes. As readily suspected, competitive debromoboration of 2 to revert to the starting alkynes would be the main cause of difficulty in the Pd-catalyzed cross-Coupling of 2, and the fact that those derived from aryl- and alkenyl-substituted ethynes are benzylic and allylic bromides, respectively, besides being alkenyl bromides must undoubtedly be responsible for their significantly higher propensity to undergoing debromoboration, as compared with that of alkylethyne-derived 2. Thus, for example, the reaction of 2a, generated by bromoboration of phenylethyne followed by treatment with pinacol, with (E)-1-octenylzinc bromide in the presence of Pd(DPEphos)Cl2 (0.5 mol %) at 23 °C for 2 h led to the formation of the desired 3a in <2% yield along with PhC≡CH (20%) and the unreacted 2a (67%). The results indicate that the reaction not only is slow but also produces at least ten times as much PhC≡CH as 3a. To our delight, however, the use of highly active Pd catalysts, such as Pd(tBu3P)2[11,12] and PEPPSI™-IPr (5),[12c,13,14] almost fully suppressed debromoboration of 2a and led to the production of the desired 3a of ≥98% isomeric purity in high yields along with only traces (<2%) of PhC≡CH and the unreacted starting compound 2a (Eq. 1 in Scheme 2). Earlier in this study, we treated 2b (Y = Br) with nHexZnBr in THF in the presence of 0.5 mol % of Pd(tBu3P)2 and obtained, after iodinolysis, the desired (E)-α-(n-hexyl)-β-iodostyrene (4b) only in 14% yield along with PhC=CH formed in 78% yield (Eq. 2 in Scheme 2). However, the use of Pd(tBu3P)2 as a catalyst later proved to be appropriate, since its use along with 2a in place of 2b gave 4b in 86% yield (Eq. 3 in Scheme 2). The results shown in Scheme 2 clearly indicate that proper selection of not only Pd catalysts, e.g., Pd(tBu3P)2 and PEPPSI™-IPr (5), but also boryl groups, e.g., pinacolboryl rather than dibromoboryl, is critically important. Scheme 2 Pd-Catalyzed cross-Coupling reactions of (Z)-β-bromo-β-phenylethenylboranes (2a and 2b). Effects of Pd catalysts and boryl groups. Cond. I: i) BBr3 (1.1 equiv), CH2Cl2, −78 °C, 1 h; ii) pinacol (1.2 equiv), iPr2NEt (2.4 ... As summarized in Table 1, a wide range of R2 groups including alkyl, alkenyl, aryl, and alkynyl may now be introduced into 3 and 4 derived from aryletheynes, such as phenylethyne, p-chlorophenylethyne, and p-tolylethyne, by using (i) (Z)-β-aryl-β-bromoalkenyl(pinacol)boranes (2), (ii) either Pd(tBu3P)2 or PEPPSI™-IPr (5). Since a wide range of Pd-catalyzed alkenylation reactions are known to selectively and satisfactorily convert alkenylmetals and/or alkenyl halides represented by 3 and 4 into the corresponding trisubstituted alkenes 1[4,15] our attention in this study is focused on the synthesis of 3 and 4. Many of the alkenes represented by 3 and 4 shown in Table 1 are very difficult to prepare in a highly (≥98%) selective manner by any previously known methods except for those that are accessible by Zr-catalyzed carboalumination[5] and carbocupration[16] of alkynes. To demonstrate the synthetic utility of the alkyne bromoboration–Pd-catalyzed cross-Coupling route to 3 and 4, a pair of (E)- and (Z)-2-iodo-1,1-diarylethenes 4h and 4i were synthesized as ≥98% stereoisomerically pure compounds in 42% and 46% yields in two steps from PhC≡CH and p-ClC6H4C≡CH, respectively (Scheme 3). Scheme 3 Highly selective (≥98%) synthesis of (E)- and (Z)-α -(p-chlorophenyl)-β-iodostyrenes (4h and 4i) via arylethyne bromoboration–Negishi Coupling–iodinolysis. Table 1 Arylethyne bromoboration–Negishi Coupling route to β,β-disubstituted alkenyl(pinacol)boranes (3) and the corresponding iodides (4). In summary, the following findings have significantly contributed to the development of the widely applicable and highly selective route to trisubstituted alkenes via alkyne elementometalation–Pd-catalyzed cross-Coupling. (1) (Z)-β-Bromo-β-arylethenyldibromoboranes, readily preparable by treatment of arylethyne with BBr3,[10] do not satisfactorily undergo Pd-catalyzed cross-Coupling due to competitive β-debromoboration under all conditions tested thus far. However, the combined use of the corresponding (Z)-β-bromo-β-arylethenyl(pinacol)boranes and highly active Pd catalysts, such as Pd(tBu3P)2[11,12] and PEPPSI™-IPr (5),[13] leads to highly (≥98%) regio- and stereoselective syntheses of the corresponding trisubstituted alkenyl(pinacol)boranes (3) in one or two steps from arylethynes via Negishi Coupling in 53 to 66% isolated overall yields. The corresponding alkenyl iodides (4) can be obtained as ≥98% isomerically pure compounds by known iodinolysis of 3 with I2 and NaOH in 80–86% isolated yields from 3. In a couple of cases, the feasibility of one-pot conversion of arylethynes to 4 in ca. 60% overall yields has also been demonstrated (Table 1). (2) The arylethyne bromoboration–Negishi Coupling protocol reported herein makes available 3 and 4, and hence their fully carbotrisubstituted derivatives as well,[4,15] many of which have been very difficult to prepare as highy (≥98%) isomerically pure compounds by any other known methods. Together with the related alkylethyne-based protocols,[7–9] the alkyne bromoboration–Negishi Coupling protocol represents the hitherto most widely applicable and highly (≥98%) selective route to trisubstituted alkenes. Further development with the use of conjugated 1,3-enynes and 1,3-diynes is currently in progress.
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Negishi Coupling—Expedient Formation of Biphenyls on the Periphery of Inorganic/Organometallic Diruthenium Species
Organometallics, 2007Co-Authors: Lei Zhang, Zhihong Huang, Weizhong Chen, Ei-ichi Negishi, Phillip E. Fanwick, James B. Updegraff, John D. Protasiewicz, Tong RenAbstract:Negishi Coupling is a facile, mild, and high-yield alternative to Suzuki Coupling in the biphenyl formation at the periphery of diruthenium coordination and organometallic compounds.
Olivier Baudoin - One of the best experts on this subject based on the ideXlab platform.
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Regiodivergent enantioselective C–H functionalization of Boc-1,3-oxazinanes for the synthesis of β^2- and β^3-amino acids
Nature Catalysis, 2019Co-Authors: Ke-feng Zhang, Olivier BaudoinAbstract:β^2- and β^3-amino acids are important chiral building blocks for the design of new pharmaceuticals and peptidomimetics. Here, we report a straightforward regio- and enantiodivergent access to these compounds using a one-pot reaction composed of sparteine-mediated enantioselective lithiation of a Boc-1,3-oxazinane, transmetallation to zinc and direct or migratory Negishi Coupling with an organic electrophile. The regioselectivity of the Negishi Coupling was highly ligand-controlled and switchable to obtain the C4- or the C5-functionalized product exclusively. High enantioselectivities were achieved on a broad range of examples, and a catalytic version in chiral diamine was developed using the (+)-sparteine surrogate. Selected C4- and C5-functionalized Boc-1,3-oxazinanes were subsequently converted to highly enantioenriched β^2- and β^3-amino acids with the ( R ) or ( S ) configuration, depending on the sparteine enantiomer employed in the lithiation step. Here the enantioselective lithiation of Boc-1,3-oxazinanes is reported. Transmetallation to zinc allows for regiodivergent functionalization at either C4 or C5 positions via a ligand-controlled Negishi Coupling, and subsequent oxidative cleavage gives easy access to both β^2- and β^3-amino acids.
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Regiodivergent enantioselective C-H functionalization of Boc-1,3-oxazinanes and application to the synthesis of β2 and β3-amino acids.
Nature catalysis, 2019Co-Authors: Weilong Lin, Ke-feng Zhang, Olivier BaudoinAbstract:β2- and β3-amino acids are important chiral building blocks for the design of new pharmaceuticals and peptidomimetics. Here, we report a straightforward regio- and enantiodivergent access to these compounds using a one-pot reaction composed of sparteine-mediated enantioselective lithiation of a Boc-1,3-oxazinane, transmetallation to zinc and direct or migratory Negishi Coupling with an organic electrophile. The regioselectivity of the Negishi Coupling was highly ligand-controlled and switchable to obtain the C4- or the C5-functionalized product exclusively. High enantioselectivities were achieved on a broad range of examples, and a catalytic version in chiral diamine was developed using the (+)-sparteine surrogate. Selected C4- and C5-functionalized Boc-1,3-oxazinanes were subsequently converted to highly enantioenriched β2- and β3-amino acids with the (R) or (S) configuration, depending on the sparteine enantiomer employed in the lithiation step. Here the enantioselective lithiation of Boc-1,3-oxazinanes is reported. Transmetallation to zinc allows for regiodivergent functionalization at either C4 or C5 positions via a ligand-controlled Negishi Coupling, and subsequent oxidative cleavage gives easy access to both β2- and β3-amino acids.
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Pd-catalyzed γ-arylation of γ,δ-unsaturated O-carbamates via an unusual haptotropic rearrangement
Chemical science, 2019Co-Authors: Titouan Royal, Olivier BaudoinAbstract:An unusual γ-selectivity was observed in the arylation of γ,δ-unsaturated O-carbamates involving directed lithiation, transmetallation to zinc and Negishi Coupling, when a specific combination of aryl electrophile and phosphine ligand is employed. Mechanistic studies indicate that an unusual, stereospecific haptotropic rearrangement of the palladium–diene intermediate is involved.
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Barbier-Negishi Coupling of Secondary Alkyl Bromides with Aryl and Alkenyl Triflates and Nonaflates.
Angewandte Chemie (International ed. in English), 2018Co-Authors: Ke-feng Zhang, Fadri Christoffel, Olivier BaudoinAbstract:A mild and practical Barbier-Negishi Coupling of secondary alkyl bromides with aryl and alkenyl triflates and nonaflates has been developed. This challenging reaction was enabled by the use of a very bulky imidazole-based phosphine ligand, which resulted in good yields as well as good chemo- and site selectivities for a broad range of substrates at room temperature and under non-aqueous conditions. This reaction was extended to primary alkyl bromides by using an analogous pyrazole-based ligand.
Chao Wang - One of the best experts on this subject based on the ideXlab platform.
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aryl ether as a Negishi Coupling partner an approach for constructing c c bonds under mild conditions
Chemistry: A European Journal, 2012Co-Authors: Chao Wang, Takashi J. Ozaki, Ryo Takita, Masanobu UchiyamaAbstract:An etheric Negishi Coupling: The first cross-Coupling reaction between aryl alkyl ethers and dianion-type zincate reagents to afford biaryl compounds through selective cleavage of the etheric C(sp(2))-O bond was developed. Dianion-type zincates showed excellent reactivity toward the aromatic ethers under mild conditions, with good functional group compatibility (see scheme).
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Aryl Ether as a Negishi Coupling Partner: An Approach for Constructing C ? C Bonds under Mild Conditions
Chemistry (Weinheim an der Bergstrasse Germany), 2012Co-Authors: Chao Wang, Takashi J. Ozaki, Ryo Takita, Masanobu UchiyamaAbstract:An etheric Negishi Coupling: The first cross-Coupling reaction between aryl alkyl ethers and dianion-type zincate reagents to afford biaryl compounds through selective cleavage of the etheric C(sp(2))-O bond was developed. Dianion-type zincates showed excellent reactivity toward the aromatic ethers under mild conditions, with good functional group compatibility (see scheme).
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arylethyne bromoboration Negishi Coupling route to e or z aryl substituted trisubstituted alkenes of 98 isomeric purity new horizon in the highly selective synthesis of trisubstituted alkenes
Advanced Synthesis & Catalysis, 2010Co-Authors: Chao Wang, Tomas Tobrman, Ei-ichi NegishiAbstract:Despite major advances in the syntheses of strictly (≥98%) regio- and stereodefined alkenes via “elementometalation”[1]–Pd- or Ni-catalyzed cross-Coupling developed since 1976,[2]-[4] efficient and highly (≥98%) selective syntheses of tri- and tetrasubstituted alkenes continue to provide major synthetic challenges. The Zr-catalyzed alkyne carboalumination–Negishi Coupling[3][4] (Eq. 1 in Scheme 1) has provided a highly selective and widely used method for the synthesis of trisubstituted alkenes.[4b] Although this method is broad in synthetic scope with respect to R1 of the starting alkyne (R1C≡CH), the R2 group of the organoalanes to be added to R1C≡CH has been practically limited to Me, and a limited number of alkyl groups including allyl and benzyl groups.[3–6] On the other hand, in an alkyne bromoboration–Negishi-Suzuki tandem cross-Coupling process (Eq. 2 in Scheme 1) reported by Suzuki in 1988,[7] bromoboration of R1C≡CH is followed by incorporation of both R2 and R3 groups by Pd-catalyzed cross-Coupling reactions of wide synthetic scopes, thereby promising to provide a method of very wide applicability for synthesizing trisubstituted alkenes. In reality, however, all reported examples[7] of Eq. 2 in Scheme 1 and of its modification involving double Negishi Coupling reactions[8,9] (Eq. 3 in Scheme 1) involve the use of only alkylethynes, even though haloboration of aryl- and alkenyl-substituted ethynes are known to proceed well.[10] Scheme 1 Highly (≥98%) selective “elementometalation” –Pd-catalyzed cross-Coupling routes to trisubstituted alkenes. As readily suspected, competitive debromoboration of 2 to revert to the starting alkynes would be the main cause of difficulty in the Pd-catalyzed cross-Coupling of 2, and the fact that those derived from aryl- and alkenyl-substituted ethynes are benzylic and allylic bromides, respectively, besides being alkenyl bromides must undoubtedly be responsible for their significantly higher propensity to undergoing debromoboration, as compared with that of alkylethyne-derived 2. Thus, for example, the reaction of 2a, generated by bromoboration of phenylethyne followed by treatment with pinacol, with (E)-1-octenylzinc bromide in the presence of Pd(DPEphos)Cl2 (0.5 mol %) at 23 °C for 2 h led to the formation of the desired 3a in <2% yield along with PhC≡CH (20%) and the unreacted 2a (67%). The results indicate that the reaction not only is slow but also produces at least ten times as much PhC≡CH as 3a. To our delight, however, the use of highly active Pd catalysts, such as Pd(tBu3P)2[11,12] and PEPPSI™-IPr (5),[12c,13,14] almost fully suppressed debromoboration of 2a and led to the production of the desired 3a of ≥98% isomeric purity in high yields along with only traces (<2%) of PhC≡CH and the unreacted starting compound 2a (Eq. 1 in Scheme 2). Earlier in this study, we treated 2b (Y = Br) with nHexZnBr in THF in the presence of 0.5 mol % of Pd(tBu3P)2 and obtained, after iodinolysis, the desired (E)-α-(n-hexyl)-β-iodostyrene (4b) only in 14% yield along with PhC=CH formed in 78% yield (Eq. 2 in Scheme 2). However, the use of Pd(tBu3P)2 as a catalyst later proved to be appropriate, since its use along with 2a in place of 2b gave 4b in 86% yield (Eq. 3 in Scheme 2). The results shown in Scheme 2 clearly indicate that proper selection of not only Pd catalysts, e.g., Pd(tBu3P)2 and PEPPSI™-IPr (5), but also boryl groups, e.g., pinacolboryl rather than dibromoboryl, is critically important. Scheme 2 Pd-Catalyzed cross-Coupling reactions of (Z)-β-bromo-β-phenylethenylboranes (2a and 2b). Effects of Pd catalysts and boryl groups. Cond. I: i) BBr3 (1.1 equiv), CH2Cl2, −78 °C, 1 h; ii) pinacol (1.2 equiv), iPr2NEt (2.4 ... As summarized in Table 1, a wide range of R2 groups including alkyl, alkenyl, aryl, and alkynyl may now be introduced into 3 and 4 derived from aryletheynes, such as phenylethyne, p-chlorophenylethyne, and p-tolylethyne, by using (i) (Z)-β-aryl-β-bromoalkenyl(pinacol)boranes (2), (ii) either Pd(tBu3P)2 or PEPPSI™-IPr (5). Since a wide range of Pd-catalyzed alkenylation reactions are known to selectively and satisfactorily convert alkenylmetals and/or alkenyl halides represented by 3 and 4 into the corresponding trisubstituted alkenes 1[4,15] our attention in this study is focused on the synthesis of 3 and 4. Many of the alkenes represented by 3 and 4 shown in Table 1 are very difficult to prepare in a highly (≥98%) selective manner by any previously known methods except for those that are accessible by Zr-catalyzed carboalumination[5] and carbocupration[16] of alkynes. To demonstrate the synthetic utility of the alkyne bromoboration–Pd-catalyzed cross-Coupling route to 3 and 4, a pair of (E)- and (Z)-2-iodo-1,1-diarylethenes 4h and 4i were synthesized as ≥98% stereoisomerically pure compounds in 42% and 46% yields in two steps from PhC≡CH and p-ClC6H4C≡CH, respectively (Scheme 3). Scheme 3 Highly selective (≥98%) synthesis of (E)- and (Z)-α -(p-chlorophenyl)-β-iodostyrenes (4h and 4i) via arylethyne bromoboration–Negishi Coupling–iodinolysis. Table 1 Arylethyne bromoboration–Negishi Coupling route to β,β-disubstituted alkenyl(pinacol)boranes (3) and the corresponding iodides (4). In summary, the following findings have significantly contributed to the development of the widely applicable and highly selective route to trisubstituted alkenes via alkyne elementometalation–Pd-catalyzed cross-Coupling. (1) (Z)-β-Bromo-β-arylethenyldibromoboranes, readily preparable by treatment of arylethyne with BBr3,[10] do not satisfactorily undergo Pd-catalyzed cross-Coupling due to competitive β-debromoboration under all conditions tested thus far. However, the combined use of the corresponding (Z)-β-bromo-β-arylethenyl(pinacol)boranes and highly active Pd catalysts, such as Pd(tBu3P)2[11,12] and PEPPSI™-IPr (5),[13] leads to highly (≥98%) regio- and stereoselective syntheses of the corresponding trisubstituted alkenyl(pinacol)boranes (3) in one or two steps from arylethynes via Negishi Coupling in 53 to 66% isolated overall yields. The corresponding alkenyl iodides (4) can be obtained as ≥98% isomerically pure compounds by known iodinolysis of 3 with I2 and NaOH in 80–86% isolated yields from 3. In a couple of cases, the feasibility of one-pot conversion of arylethynes to 4 in ca. 60% overall yields has also been demonstrated (Table 1). (2) The arylethyne bromoboration–Negishi Coupling protocol reported herein makes available 3 and 4, and hence their fully carbotrisubstituted derivatives as well,[4,15] many of which have been very difficult to prepare as highy (≥98%) isomerically pure compounds by any other known methods. Together with the related alkylethyne-based protocols,[7–9] the alkyne bromoboration–Negishi Coupling protocol represents the hitherto most widely applicable and highly (≥98%) selective route to trisubstituted alkenes. Further development with the use of conjugated 1,3-enynes and 1,3-diynes is currently in progress.
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Arylethyne Bromoboration–Negishi Coupling Route to E- or Z-Aryl-Substituted Trisubstituted Alkenes of ≥98% Isomeric Purity. New Horizon in the Highly Selective Synthesis of Trisubstituted Alkenes
Advanced synthesis & catalysis, 2010Co-Authors: Chao Wang, Tomas Tobrman, Ei-ichi NegishiAbstract:Despite major advances in the syntheses of strictly (≥98%) regio- and stereodefined alkenes via “elementometalation”[1]–Pd- or Ni-catalyzed cross-Coupling developed since 1976,[2]-[4] efficient and highly (≥98%) selective syntheses of tri- and tetrasubstituted alkenes continue to provide major synthetic challenges. The Zr-catalyzed alkyne carboalumination–Negishi Coupling[3][4] (Eq. 1 in Scheme 1) has provided a highly selective and widely used method for the synthesis of trisubstituted alkenes.[4b] Although this method is broad in synthetic scope with respect to R1 of the starting alkyne (R1C≡CH), the R2 group of the organoalanes to be added to R1C≡CH has been practically limited to Me, and a limited number of alkyl groups including allyl and benzyl groups.[3–6] On the other hand, in an alkyne bromoboration–Negishi-Suzuki tandem cross-Coupling process (Eq. 2 in Scheme 1) reported by Suzuki in 1988,[7] bromoboration of R1C≡CH is followed by incorporation of both R2 and R3 groups by Pd-catalyzed cross-Coupling reactions of wide synthetic scopes, thereby promising to provide a method of very wide applicability for synthesizing trisubstituted alkenes. In reality, however, all reported examples[7] of Eq. 2 in Scheme 1 and of its modification involving double Negishi Coupling reactions[8,9] (Eq. 3 in Scheme 1) involve the use of only alkylethynes, even though haloboration of aryl- and alkenyl-substituted ethynes are known to proceed well.[10] Scheme 1 Highly (≥98%) selective “elementometalation” –Pd-catalyzed cross-Coupling routes to trisubstituted alkenes. As readily suspected, competitive debromoboration of 2 to revert to the starting alkynes would be the main cause of difficulty in the Pd-catalyzed cross-Coupling of 2, and the fact that those derived from aryl- and alkenyl-substituted ethynes are benzylic and allylic bromides, respectively, besides being alkenyl bromides must undoubtedly be responsible for their significantly higher propensity to undergoing debromoboration, as compared with that of alkylethyne-derived 2. Thus, for example, the reaction of 2a, generated by bromoboration of phenylethyne followed by treatment with pinacol, with (E)-1-octenylzinc bromide in the presence of Pd(DPEphos)Cl2 (0.5 mol %) at 23 °C for 2 h led to the formation of the desired 3a in
Niousha Nazari - One of the best experts on this subject based on the ideXlab platform.
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Negishi Coupling: an easy progress for C–C bond construction in total synthesis
Molecular Diversity, 2014Co-Authors: Majid M. Heravi, Elaheh Hashemi, Niousha NazariAbstract:Negishi cross-Coupling reactions were used extensively in total synthesis. The expansion of substrate scope, the development of mild reaction conditions, the advancement of the methods to improve the stereo- and regio-selectivity of carbon–carbon bond formation, the maturity of a large number of sequential processes, and the development of non-toxic reactions signify the importance of Negishi Coupling. The following review illustrates a strategic role of this reaction in constructing carbon–carbon bonds in the recent total synthesis of natural products.
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Negishi Coupling: an easy progress for C-C bond construction in total synthesis.
Molecular diversity, 2014Co-Authors: Majid M. Heravi, Elaheh Hashemi, Niousha NazariAbstract:Negishi cross-Coupling reactions were used extensively in total synthesis. The expansion of substrate scope, the development of mild reaction conditions, the advancement of the methods to improve the stereo- and regio-selectivity of carbon–carbon bond formation, the maturity of a large number of sequential processes, and the development of non-toxic reactions signify the importance of Negishi Coupling. The following review illustrates a strategic role of this reaction in constructing carbon–carbon bonds in the recent total synthesis of natural products.
Tomas Tobrman - One of the best experts on this subject based on the ideXlab platform.
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arylethyne bromoboration Negishi Coupling route to e or z aryl substituted trisubstituted alkenes of 98 isomeric purity new horizon in the highly selective synthesis of trisubstituted alkenes
Advanced Synthesis & Catalysis, 2010Co-Authors: Chao Wang, Tomas Tobrman, Ei-ichi NegishiAbstract:Despite major advances in the syntheses of strictly (≥98%) regio- and stereodefined alkenes via “elementometalation”[1]–Pd- or Ni-catalyzed cross-Coupling developed since 1976,[2]-[4] efficient and highly (≥98%) selective syntheses of tri- and tetrasubstituted alkenes continue to provide major synthetic challenges. The Zr-catalyzed alkyne carboalumination–Negishi Coupling[3][4] (Eq. 1 in Scheme 1) has provided a highly selective and widely used method for the synthesis of trisubstituted alkenes.[4b] Although this method is broad in synthetic scope with respect to R1 of the starting alkyne (R1C≡CH), the R2 group of the organoalanes to be added to R1C≡CH has been practically limited to Me, and a limited number of alkyl groups including allyl and benzyl groups.[3–6] On the other hand, in an alkyne bromoboration–Negishi-Suzuki tandem cross-Coupling process (Eq. 2 in Scheme 1) reported by Suzuki in 1988,[7] bromoboration of R1C≡CH is followed by incorporation of both R2 and R3 groups by Pd-catalyzed cross-Coupling reactions of wide synthetic scopes, thereby promising to provide a method of very wide applicability for synthesizing trisubstituted alkenes. In reality, however, all reported examples[7] of Eq. 2 in Scheme 1 and of its modification involving double Negishi Coupling reactions[8,9] (Eq. 3 in Scheme 1) involve the use of only alkylethynes, even though haloboration of aryl- and alkenyl-substituted ethynes are known to proceed well.[10] Scheme 1 Highly (≥98%) selective “elementometalation” –Pd-catalyzed cross-Coupling routes to trisubstituted alkenes. As readily suspected, competitive debromoboration of 2 to revert to the starting alkynes would be the main cause of difficulty in the Pd-catalyzed cross-Coupling of 2, and the fact that those derived from aryl- and alkenyl-substituted ethynes are benzylic and allylic bromides, respectively, besides being alkenyl bromides must undoubtedly be responsible for their significantly higher propensity to undergoing debromoboration, as compared with that of alkylethyne-derived 2. Thus, for example, the reaction of 2a, generated by bromoboration of phenylethyne followed by treatment with pinacol, with (E)-1-octenylzinc bromide in the presence of Pd(DPEphos)Cl2 (0.5 mol %) at 23 °C for 2 h led to the formation of the desired 3a in <2% yield along with PhC≡CH (20%) and the unreacted 2a (67%). The results indicate that the reaction not only is slow but also produces at least ten times as much PhC≡CH as 3a. To our delight, however, the use of highly active Pd catalysts, such as Pd(tBu3P)2[11,12] and PEPPSI™-IPr (5),[12c,13,14] almost fully suppressed debromoboration of 2a and led to the production of the desired 3a of ≥98% isomeric purity in high yields along with only traces (<2%) of PhC≡CH and the unreacted starting compound 2a (Eq. 1 in Scheme 2). Earlier in this study, we treated 2b (Y = Br) with nHexZnBr in THF in the presence of 0.5 mol % of Pd(tBu3P)2 and obtained, after iodinolysis, the desired (E)-α-(n-hexyl)-β-iodostyrene (4b) only in 14% yield along with PhC=CH formed in 78% yield (Eq. 2 in Scheme 2). However, the use of Pd(tBu3P)2 as a catalyst later proved to be appropriate, since its use along with 2a in place of 2b gave 4b in 86% yield (Eq. 3 in Scheme 2). The results shown in Scheme 2 clearly indicate that proper selection of not only Pd catalysts, e.g., Pd(tBu3P)2 and PEPPSI™-IPr (5), but also boryl groups, e.g., pinacolboryl rather than dibromoboryl, is critically important. Scheme 2 Pd-Catalyzed cross-Coupling reactions of (Z)-β-bromo-β-phenylethenylboranes (2a and 2b). Effects of Pd catalysts and boryl groups. Cond. I: i) BBr3 (1.1 equiv), CH2Cl2, −78 °C, 1 h; ii) pinacol (1.2 equiv), iPr2NEt (2.4 ... As summarized in Table 1, a wide range of R2 groups including alkyl, alkenyl, aryl, and alkynyl may now be introduced into 3 and 4 derived from aryletheynes, such as phenylethyne, p-chlorophenylethyne, and p-tolylethyne, by using (i) (Z)-β-aryl-β-bromoalkenyl(pinacol)boranes (2), (ii) either Pd(tBu3P)2 or PEPPSI™-IPr (5). Since a wide range of Pd-catalyzed alkenylation reactions are known to selectively and satisfactorily convert alkenylmetals and/or alkenyl halides represented by 3 and 4 into the corresponding trisubstituted alkenes 1[4,15] our attention in this study is focused on the synthesis of 3 and 4. Many of the alkenes represented by 3 and 4 shown in Table 1 are very difficult to prepare in a highly (≥98%) selective manner by any previously known methods except for those that are accessible by Zr-catalyzed carboalumination[5] and carbocupration[16] of alkynes. To demonstrate the synthetic utility of the alkyne bromoboration–Pd-catalyzed cross-Coupling route to 3 and 4, a pair of (E)- and (Z)-2-iodo-1,1-diarylethenes 4h and 4i were synthesized as ≥98% stereoisomerically pure compounds in 42% and 46% yields in two steps from PhC≡CH and p-ClC6H4C≡CH, respectively (Scheme 3). Scheme 3 Highly selective (≥98%) synthesis of (E)- and (Z)-α -(p-chlorophenyl)-β-iodostyrenes (4h and 4i) via arylethyne bromoboration–Negishi Coupling–iodinolysis. Table 1 Arylethyne bromoboration–Negishi Coupling route to β,β-disubstituted alkenyl(pinacol)boranes (3) and the corresponding iodides (4). In summary, the following findings have significantly contributed to the development of the widely applicable and highly selective route to trisubstituted alkenes via alkyne elementometalation–Pd-catalyzed cross-Coupling. (1) (Z)-β-Bromo-β-arylethenyldibromoboranes, readily preparable by treatment of arylethyne with BBr3,[10] do not satisfactorily undergo Pd-catalyzed cross-Coupling due to competitive β-debromoboration under all conditions tested thus far. However, the combined use of the corresponding (Z)-β-bromo-β-arylethenyl(pinacol)boranes and highly active Pd catalysts, such as Pd(tBu3P)2[11,12] and PEPPSI™-IPr (5),[13] leads to highly (≥98%) regio- and stereoselective syntheses of the corresponding trisubstituted alkenyl(pinacol)boranes (3) in one or two steps from arylethynes via Negishi Coupling in 53 to 66% isolated overall yields. The corresponding alkenyl iodides (4) can be obtained as ≥98% isomerically pure compounds by known iodinolysis of 3 with I2 and NaOH in 80–86% isolated yields from 3. In a couple of cases, the feasibility of one-pot conversion of arylethynes to 4 in ca. 60% overall yields has also been demonstrated (Table 1). (2) The arylethyne bromoboration–Negishi Coupling protocol reported herein makes available 3 and 4, and hence their fully carbotrisubstituted derivatives as well,[4,15] many of which have been very difficult to prepare as highy (≥98%) isomerically pure compounds by any other known methods. Together with the related alkylethyne-based protocols,[7–9] the alkyne bromoboration–Negishi Coupling protocol represents the hitherto most widely applicable and highly (≥98%) selective route to trisubstituted alkenes. Further development with the use of conjugated 1,3-enynes and 1,3-diynes is currently in progress.
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Arylethyne Bromoboration–Negishi Coupling Route to E- or Z-Aryl-Substituted Trisubstituted Alkenes of ≥98% Isomeric Purity. New Horizon in the Highly Selective Synthesis of Trisubstituted Alkenes
Advanced synthesis & catalysis, 2010Co-Authors: Chao Wang, Tomas Tobrman, Ei-ichi NegishiAbstract:Despite major advances in the syntheses of strictly (≥98%) regio- and stereodefined alkenes via “elementometalation”[1]–Pd- or Ni-catalyzed cross-Coupling developed since 1976,[2]-[4] efficient and highly (≥98%) selective syntheses of tri- and tetrasubstituted alkenes continue to provide major synthetic challenges. The Zr-catalyzed alkyne carboalumination–Negishi Coupling[3][4] (Eq. 1 in Scheme 1) has provided a highly selective and widely used method for the synthesis of trisubstituted alkenes.[4b] Although this method is broad in synthetic scope with respect to R1 of the starting alkyne (R1C≡CH), the R2 group of the organoalanes to be added to R1C≡CH has been practically limited to Me, and a limited number of alkyl groups including allyl and benzyl groups.[3–6] On the other hand, in an alkyne bromoboration–Negishi-Suzuki tandem cross-Coupling process (Eq. 2 in Scheme 1) reported by Suzuki in 1988,[7] bromoboration of R1C≡CH is followed by incorporation of both R2 and R3 groups by Pd-catalyzed cross-Coupling reactions of wide synthetic scopes, thereby promising to provide a method of very wide applicability for synthesizing trisubstituted alkenes. In reality, however, all reported examples[7] of Eq. 2 in Scheme 1 and of its modification involving double Negishi Coupling reactions[8,9] (Eq. 3 in Scheme 1) involve the use of only alkylethynes, even though haloboration of aryl- and alkenyl-substituted ethynes are known to proceed well.[10] Scheme 1 Highly (≥98%) selective “elementometalation” –Pd-catalyzed cross-Coupling routes to trisubstituted alkenes. As readily suspected, competitive debromoboration of 2 to revert to the starting alkynes would be the main cause of difficulty in the Pd-catalyzed cross-Coupling of 2, and the fact that those derived from aryl- and alkenyl-substituted ethynes are benzylic and allylic bromides, respectively, besides being alkenyl bromides must undoubtedly be responsible for their significantly higher propensity to undergoing debromoboration, as compared with that of alkylethyne-derived 2. Thus, for example, the reaction of 2a, generated by bromoboration of phenylethyne followed by treatment with pinacol, with (E)-1-octenylzinc bromide in the presence of Pd(DPEphos)Cl2 (0.5 mol %) at 23 °C for 2 h led to the formation of the desired 3a in
