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Enantioselective 1,4-additions of QCHR) (R = alkyl, alkenyl, Ph) ClMeAl(CHQ to cyclohexenones†
Received 25th October 2013, Accepted 19th November 2013
D. Willcox,a S. Woodward*a and A. Alexakisb
DOI: 10.1039/c3cc48191c www.rsc.org/chemcomm
QCHR) prepared directly Chloromethylvinyl alanes (E)-ClMeAl(CHQ from terminal alkynes undergo 1,4-addition to cyclohexenone and 3-methylcyclohexenone in moderate to good yield (30–70%) and good to excellent stereoselectivity (80–98% ee) using readily available copper(I) sources and chiral ligands.
Asymmetric conjugate addition (ACA) has become a mainstay of contemporary chiral synthesis in the last 10 years.1 Sublime levels of enantioselectivity are realised in 1,4-additions of simple alkyl groups to various Michael acceptors, but the situation for C(sp2) vinyl-based nucleophiles is not so clear cut. Rhodium-diphosphine catalysts are normally preferred for additions of C(sp2) nucleophiles, especially aryls, to mono substituted enones2 but these fail to elicit any reaction for b,b-substituted enones – where copper(I)/phosphorus-ligand catalysts are required.1,3 The choice of C(sp2) nucleophile also has issues: vinyl boronic acids, and their derivatives, are rather more susceptible to hydrolytic deboronation compared to their aryl cousins – causing lower yields or the need for excess reagents. Alkenylalanes, used with CuI catalysts, are often prepared from RCCH and DIBAL-H (either through heating,4 or Ni-catalysis5) have issues: (i) deprotonation by-products are common under thermal DIBAL-H procedures except for alkyl substituted cases; (ii) b-aryl Bui2AlCHQCHAr, prepared by Ni-catalysis, are normally contaminated with B5% of the a-aryl isomer; finally (iii) the bulky Bui substituents can cause problems in the subsequent ACA catalysis leading to low yields and slow reactions. Alternative hydroalumination-ACA approaches are desirable, particularly if they use simple reagents catalysts and conditions to deliver high ee values for 1,4-additions to both mono and b,b-disubstituted enones. a
School of Chemistry, The University of Nottingham, University Park, Nottingham, UK. E-mail: [email protected]; Fax: +44 (0)115 9513564; Tel: +44 (0)115 9513541 b Department of Organic Chemistry, University of Geneva, Quai Ernest Ansermet 30, CH-1211 Geneva 4, Switzerland † Electronic supplementary information (ESI) available. See DOI: 10.1039/ c3cc48191c
This journal is © The Royal Society of Chemistry 2014
We were attracted to the terminal alkyne hydroalumination products derived from the appreciably stabilised, easily prepared hydride HAlCl2(THF)2;6 e.g. Cp*2ZrCl2 (2–5 mol%) (Cp* = Z5-C5Me5) affords (E)-Cl2AlCHQCHC6H13 (1a) quantitatively from HCRCC6H13. Preliminary trials indicated the absence of background reactions of 1a with cyclohexenone.7 Reaction of 1a with cyclohexenone is highly accelerated by CuTC/PCy3 (5–10 mol%; TC = 2-thiophenecarboxylate) at 30 1C but this provides an enone trimerisation product‡ by a mechanism identical to that we demonstrated earlier for PhCH2ZnBr.8 This trimeric by-product originates from slow transmetalation of the post-ACA Cu-bound enolate by fresh 1a. Improving the nucleophilicity of 1a is therefore predicted to overcome this. Co-promotion of 1a with AlMe3 and running the reaction at 25 1C led to chemoselective formation of 1,4-addition products. However, under CuI/chiral phosphorus ligand catalysis the maximum ee value attained was o55% for a library of 17 ligands. Fortunately, when treated with MeLi (1.0 equiv.) 1a provided an alane (nominally (E)-ClAlMeCHQCHC6H13)§ leading to ee values (>80%) with readily available Feringa’s ligand L1. Strangely, use of two equivalents of MeLi gave poor processes (o12% yield, o5% ee) – despite the known efficacy of Me2AlCHQCHR species in related processes.9 Finally, the addition mode for 1a/MeLi to cyclohexenone was optimised (Table 1). Although higher enantioselectivities were attained (runs 1 and 5), we optimised on yield of 2a as poor chemical yields are often a more challenging problem in copper(I)-catalysed 1,4-additions of alkenyls than enantioselectivity.10 The mass balance of the reactions was enone trimerisation.‡ Taking the best compromise a range of copper(I) catalyst precursors were screened (Table 2) using the conditions of Table 1 (slow addition of cyclohexenone, run 3). In all cases the yields of 2a attained with CuI precursors other than CuTC (run 5) were lower. Although high enantioselectivity was attained using Fletcher’s conditions10 only trivial amounts of product were attained. In this, and all other cases, running the reactions for longer times (>1 h) did not improve the situation (product decomposition occurred instead). Having confirmed that the CuTC system was optimal for chemoselectivity,
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Table 1
Yield and ee effects of addition modesa
Run
Addition mode
Yield 2a (%)
ee (%)
Run
Ligand
Yield 2a (%)
ee (%)
1 2 3 4 5
Normal (enone to 1a + MeLi) Reverse (1a + MeLi to enone) Slow addition of enone Slow addition of 1a + MeLi Enone (1a + MeLi) slow addition
54 70 66 o5 20
84 60 76 n.d.b 90
1 2 3 4 5 6 7 8 9
L1 L2 L3 L4 L5 L6 L7 L8 L9
62 65 65 81 63 54 84 36 49
76 88 38 56 50 44 42 10 6
Table 3
a
Active alane from 1a (1.4 mmol) and MeLi (0.65 mmol); cyclohexenone (0.5 mmol) in toluene/tBuOMe (2.5 mL/0.5 mL). The structure of L1 is shown in Scheme 1. Yield and ee determination by GC. b Not determined.
Table 2
Copper pre-catalyst effects on the formation of 2aa
Run
Copper salt
Yield 2a (%)
ee (%)
1 2 3 4 5
Cu(OTf)2 (CuOTf)2PhMe Cu(MeCN)4BF4 CuCl + AgNTf2 (15 mol%) CuTC
6 47 34 7 66
64 78 80 90 76
a
Using the conditions of Table 1. Yield and ee determination by GC.
ease of use and activity, the enantioselectivity as a function of ligand structure was optimised. On the basis of the known trend the ligand library of Scheme 1 was selected to compare against L1. Use of 2-naphthyl units in phosphoramidites L2–L3 is often favourable in enantioselective 1,4-alane addition.11 Similarly, the ‘simplephos’ ligands L4–L9 are often effective.12 The results of this screening are presented in Table 3. Unusually in this case, the phosphoramidite L2 was optimal (run 2) compared to the tropos ligand L3 and the simplephos derivatives (L4–L9). The optimal catalytic system (CuTC/L2) was then applied to a combination of acceptors and vinylalanes (Scheme 2).
Scheme 1
Ligands used in this study.
1656 | Chem. Commun., 2014, 50, 1655--1657
a
Ligand structure effectsa
Using the conditions of Table 1. Yield and ee determination by GC.
Satisfyingly, the final process shows rather good generality in 1,4-additions to cyclohexenone (leading to 2) and to 3-substituted cyclohexenones (leading to 3–4) and even easily deprotonated terminal alkynes (required for 2c, 2d, 2f and 3c) are tolerated.¶ Only very temperamental cyclopropylacetylene derived 3g gave modest yields. An identical CuTC/L2 catalyst provides practical levels of enantioselectivity for formation of both 2 (80–96% ee) and 3 (88–98% ee). Previously mixed success has been attained in cyclohexanone alkenylation with related Cu-catalysts. For example, ACA addition of Me2AlCHQCHPh to cyclohexenone proceeds with rather poor ee (17%).13 However, high selectivities (B90% ee) are attained in a ACA reactions of a,b-unsaturated lactams and dehydro-4-piperidones (whether 3-substituted or not).14 Based on known correlations15 (S,R,R)-L2 provides (+)-(S)-2a and the other addition products are assumed to proceed with
Scheme 2 Scope of the hydroalumination–ACA process; series 2 from cyclohexenone, 3 from 3-methylcyclohexenone, 4 from 3-ethyl cyclohexenone.
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in Et2O afforded nominal ClAlMe(CHQCHBu) (1.4 equiv.). The alane solution was added to CuTC (0.05 equiv.) mixed with L2 (0.075 equiv.) in toluene and cyclohexenone (0.5 equiv.) added slowly. After 1 h at 25 1C the reaction was quenched and worked up in the normal way to afford 2a (65%, 88% ee).
Scheme 3 Hydroalumination–ACA product yields from acyclic enones and for MeAlClCHQCHTMS addition.
the same facial selectivity. Preliminary studies indicate that the scope of the reaction could be partially extended to products 5–7 (in the racemic sense), derived from linear enones (Scheme 3) and via hydroalumination of problematic Me3SiCCH (leading to 8). However, the present conditions do not provide synthetically useful isolable yields – this is under further investigation at present and will be reported later. In conclusion, simple ambient temperature ACA addition to cyclohexenones of terminal alkyne derived ClAlMeCHQCHR gives moderate to good chemical yields in synthetically useful ee values. The latter are readily available from hydroalumination with significantly air stabilised HAlCl2(THF)2.6 SW and DW gratefully acknowledge the Engineering and Physical Sciences (EPSRC; EP/G026882/1) Research Council and the University of Nottingham for funding. SW thanks AA for many fruitful collaborations over the last 20 years and wishes him a diverse and productive retirement.
Notes and references ‡ The structure of the by-product is:
§ The formation of the alternative ‘ate’ species Li[Cl2AlMeCHQCHC6H13] was discounted on the basis of the formation of copious LiCl precipitates. ¶ Representative procedure for the formation of 2a. 1-Octyne was treated with HAlCl2(THF)2 (1.4 equiv.) and Cp*2ZrCl2 (0.05 equiv.) at 80 1C (2 h) in THF followed by solvent removal and the addition of MeLi
This journal is © The Royal Society of Chemistry 2014
1 General overviews of ACA reactions: (a) A. Alexakis, N. Krause and S. Woodward, in Copper Catalysed Asymmetric Synthesis, ed. A. Alexakis, N. Krause and S. Woodward, Wiley-VCH, Weinheim, ¨ller and A. Alexakis, Chem. Com2014, ch. 2, pp. 33–68; (b) D. Mu mun., 2012, 48, 12037; (c) Catalytic Asymmetric Conjugate Reactions, ed. A. Cordova, Wiley-VCH, Weinheim, 2010; (d) S. R. Harutyunyan, T. den Hartog, K. Geurts, A. J. Minnaard and B. L. Feringa, Chem. ¨ckvall, N. Krause, Rev., 2008, 108, 2824; (e) A. Alexakis, J. E. Ba `mies and M. Die ´guez, Chem. Rev., 2008, 108, 2796; O. Pa ´mies and M. Die ´guez, Top. Organomet. Chem., 2013, ( f ) O. Pa 41, 277 and references therein. 2 Rh-catalysed alkenylation (arylation): (a) T. Hayashi and K. Yamasaki, Chem. Rev., 2003, 103, 2829 (overview); (b) T. Hayashi, K. Ueyama, N. Tokunaga and K. J. Yoshida, J. Am. Chem. Soc., 2003, 125, 11508; (c) T. Hayashi, M. Takahashi, Y. Takaya and M. Ogasawara, J. Am. Chem. Soc., 2002, 124, 5052; (d) S. Oi, T. Sato and Y. Inoue, Tetrahedron Lett., 2004, 45, 5051. 3 Cu-catalysed quaternary centre formation: (a) C. Hawner and ¨ller A. Alexakis, Chem. Commun., 2010, 46, 7295 (overview); (b) D. Mu and A. Alexakis, Org. Lett., 2013, 15, 1594; (c) M. Sidera, P. M. C. Roth, R. M. Maksymowicz and S. P. Fletcher, Angew. Chem., Int. Ed., 2013, ¨ller, M. Tissot and A. Alexakis, Org. Lett., 2011, 52, 7995; (d) D. Mu ¨ller and A. Alexakis, Chem.–Eur. J., 2013, 19, 15226. 13, 3040; (e) D. Mu 4 Thermal alkyne hydroalumination: E. Negishi, T. Takahashi and S. Baba, Org. Synth., 1988, 66, 60. 5 Ni-catalysed hydroalumination: K. Akiyama, F. Gao and A. H. Hoveyda, Angew. Chem., Int. Ed., 2010, 49, 419 based on the work of J. J. Eisch and M. W. Foxton, J. Org. Chem., 1971, 36, 3520. 6 P. Andrews, C. M. Latham, M. Magre, D. Willcox and S. Woodward, Chem. Commun., 2013, 49, 1488. 7 With reactive acceptors, e.g. alkylidenemalonates spontaneous additions are observed. 8 A. J. Blake, J. Shannon, J. C. Stephens and S. Woodward, Chem.–Eur. J., 2007, 13, 2462. ¨ller and A. Alexakis, Org. Lett., 2012, 14, 1842. 9 D. Mu 10 Lower 1,4-addition yields from MCHQCHR species attained by hydrometallation are unfortunately not uncommon, for example: see Table 2 in ref. 3d (3 runs o 50%); ref. 9 (5 runs o 50%) ref. 14 (30–70%). See also R. Maksymowicz, P. M. C. Roth, A. Thompson and S. P. Fletcher, Chem. Commun., 2013, 49, 4211. 11 C. Hawner, K. Li, V. Cirriez and A. Alexakis, Angew. Chem., Int. Ed., 2008, 47, 8211. ¨ller, C. Hawner, M. Tissot, L. Palais and A. Alexakis, Synlett, 12 D. Mu 2010, 1694. ¨ller, PhD thesis, University of Geneva, No. Sc. 4502, see 13 D. Mu specifically, p. 110. ¨ller and A. Alexakis, Org. Lett., 2013, 15, 828. 14 P. Cottet, D. Mu 15 J. F. Teichert and B. L. Feringa, Angew. Chem., Int. Ed., 2010, 49, 2486.
Chem. Commun., 2014, 50, 1655--1657 | 1657
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Cite this: Chem. Commun., 2014, 50, 1655
Enantioselective 1,4-additions of QCHR) (R = alkyl, alkenyl, Ph) ClMeAl(CHQ to cyclohexenones†
Received 25th October 2013, Accepted 19th November 2013
D. Willcox,a S. Woodward*a and A. Alexakisb
DOI: 10.1039/c3cc48191c www.rsc.org/chemcomm
QCHR) prepared directly Chloromethylvinyl alanes (E)-ClMeAl(CHQ from terminal alkynes undergo 1,4-addition to cyclohexenone and 3-methylcyclohexenone in moderate to good yield (30–70%) and good to excellent stereoselectivity (80–98% ee) using readily available copper(I) sources and chiral ligands.
Asymmetric conjugate addition (ACA) has become a mainstay of contemporary chiral synthesis in the last 10 years.1 Sublime levels of enantioselectivity are realised in 1,4-additions of simple alkyl groups to various Michael acceptors, but the situation for C(sp2) vinyl-based nucleophiles is not so clear cut. Rhodium-diphosphine catalysts are normally preferred for additions of C(sp2) nucleophiles, especially aryls, to mono substituted enones2 but these fail to elicit any reaction for b,b-substituted enones – where copper(I)/phosphorus-ligand catalysts are required.1,3 The choice of C(sp2) nucleophile also has issues: vinyl boronic acids, and their derivatives, are rather more susceptible to hydrolytic deboronation compared to their aryl cousins – causing lower yields or the need for excess reagents. Alkenylalanes, used with CuI catalysts, are often prepared from RCCH and DIBAL-H (either through heating,4 or Ni-catalysis5) have issues: (i) deprotonation by-products are common under thermal DIBAL-H procedures except for alkyl substituted cases; (ii) b-aryl Bui2AlCHQCHAr, prepared by Ni-catalysis, are normally contaminated with B5% of the a-aryl isomer; finally (iii) the bulky Bui substituents can cause problems in the subsequent ACA catalysis leading to low yields and slow reactions. Alternative hydroalumination-ACA approaches are desirable, particularly if they use simple reagents catalysts and conditions to deliver high ee values for 1,4-additions to both mono and b,b-disubstituted enones. a
School of Chemistry, The University of Nottingham, University Park, Nottingham, UK. E-mail: [email protected]; Fax: +44 (0)115 9513564; Tel: +44 (0)115 9513541 b Department of Organic Chemistry, University of Geneva, Quai Ernest Ansermet 30, CH-1211 Geneva 4, Switzerland † Electronic supplementary information (ESI) available. See DOI: 10.1039/ c3cc48191c
This journal is © The Royal Society of Chemistry 2014
We were attracted to the terminal alkyne hydroalumination products derived from the appreciably stabilised, easily prepared hydride HAlCl2(THF)2;6 e.g. Cp*2ZrCl2 (2–5 mol%) (Cp* = Z5-C5Me5) affords (E)-Cl2AlCHQCHC6H13 (1a) quantitatively from HCRCC6H13. Preliminary trials indicated the absence of background reactions of 1a with cyclohexenone.7 Reaction of 1a with cyclohexenone is highly accelerated by CuTC/PCy3 (5–10 mol%; TC = 2-thiophenecarboxylate) at 30 1C but this provides an enone trimerisation product‡ by a mechanism identical to that we demonstrated earlier for PhCH2ZnBr.8 This trimeric by-product originates from slow transmetalation of the post-ACA Cu-bound enolate by fresh 1a. Improving the nucleophilicity of 1a is therefore predicted to overcome this. Co-promotion of 1a with AlMe3 and running the reaction at 25 1C led to chemoselective formation of 1,4-addition products. However, under CuI/chiral phosphorus ligand catalysis the maximum ee value attained was o55% for a library of 17 ligands. Fortunately, when treated with MeLi (1.0 equiv.) 1a provided an alane (nominally (E)-ClAlMeCHQCHC6H13)§ leading to ee values (>80%) with readily available Feringa’s ligand L1. Strangely, use of two equivalents of MeLi gave poor processes (o12% yield, o5% ee) – despite the known efficacy of Me2AlCHQCHR species in related processes.9 Finally, the addition mode for 1a/MeLi to cyclohexenone was optimised (Table 1). Although higher enantioselectivities were attained (runs 1 and 5), we optimised on yield of 2a as poor chemical yields are often a more challenging problem in copper(I)-catalysed 1,4-additions of alkenyls than enantioselectivity.10 The mass balance of the reactions was enone trimerisation.‡ Taking the best compromise a range of copper(I) catalyst precursors were screened (Table 2) using the conditions of Table 1 (slow addition of cyclohexenone, run 3). In all cases the yields of 2a attained with CuI precursors other than CuTC (run 5) were lower. Although high enantioselectivity was attained using Fletcher’s conditions10 only trivial amounts of product were attained. In this, and all other cases, running the reactions for longer times (>1 h) did not improve the situation (product decomposition occurred instead). Having confirmed that the CuTC system was optimal for chemoselectivity,
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Table 1
Yield and ee effects of addition modesa
Run
Addition mode
Yield 2a (%)
ee (%)
Run
Ligand
Yield 2a (%)
ee (%)
1 2 3 4 5
Normal (enone to 1a + MeLi) Reverse (1a + MeLi to enone) Slow addition of enone Slow addition of 1a + MeLi Enone (1a + MeLi) slow addition
54 70 66 o5 20
84 60 76 n.d.b 90
1 2 3 4 5 6 7 8 9
L1 L2 L3 L4 L5 L6 L7 L8 L9
62 65 65 81 63 54 84 36 49
76 88 38 56 50 44 42 10 6
Table 3
a
Active alane from 1a (1.4 mmol) and MeLi (0.65 mmol); cyclohexenone (0.5 mmol) in toluene/tBuOMe (2.5 mL/0.5 mL). The structure of L1 is shown in Scheme 1. Yield and ee determination by GC. b Not determined.
Table 2
Copper pre-catalyst effects on the formation of 2aa
Run
Copper salt
Yield 2a (%)
ee (%)
1 2 3 4 5
Cu(OTf)2 (CuOTf)2PhMe Cu(MeCN)4BF4 CuCl + AgNTf2 (15 mol%) CuTC
6 47 34 7 66
64 78 80 90 76
a
Using the conditions of Table 1. Yield and ee determination by GC.
ease of use and activity, the enantioselectivity as a function of ligand structure was optimised. On the basis of the known trend the ligand library of Scheme 1 was selected to compare against L1. Use of 2-naphthyl units in phosphoramidites L2–L3 is often favourable in enantioselective 1,4-alane addition.11 Similarly, the ‘simplephos’ ligands L4–L9 are often effective.12 The results of this screening are presented in Table 3. Unusually in this case, the phosphoramidite L2 was optimal (run 2) compared to the tropos ligand L3 and the simplephos derivatives (L4–L9). The optimal catalytic system (CuTC/L2) was then applied to a combination of acceptors and vinylalanes (Scheme 2).
Scheme 1
Ligands used in this study.
1656 | Chem. Commun., 2014, 50, 1655--1657
a
Ligand structure effectsa
Using the conditions of Table 1. Yield and ee determination by GC.
Satisfyingly, the final process shows rather good generality in 1,4-additions to cyclohexenone (leading to 2) and to 3-substituted cyclohexenones (leading to 3–4) and even easily deprotonated terminal alkynes (required for 2c, 2d, 2f and 3c) are tolerated.¶ Only very temperamental cyclopropylacetylene derived 3g gave modest yields. An identical CuTC/L2 catalyst provides practical levels of enantioselectivity for formation of both 2 (80–96% ee) and 3 (88–98% ee). Previously mixed success has been attained in cyclohexanone alkenylation with related Cu-catalysts. For example, ACA addition of Me2AlCHQCHPh to cyclohexenone proceeds with rather poor ee (17%).13 However, high selectivities (B90% ee) are attained in a ACA reactions of a,b-unsaturated lactams and dehydro-4-piperidones (whether 3-substituted or not).14 Based on known correlations15 (S,R,R)-L2 provides (+)-(S)-2a and the other addition products are assumed to proceed with
Scheme 2 Scope of the hydroalumination–ACA process; series 2 from cyclohexenone, 3 from 3-methylcyclohexenone, 4 from 3-ethyl cyclohexenone.
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in Et2O afforded nominal ClAlMe(CHQCHBu) (1.4 equiv.). The alane solution was added to CuTC (0.05 equiv.) mixed with L2 (0.075 equiv.) in toluene and cyclohexenone (0.5 equiv.) added slowly. After 1 h at 25 1C the reaction was quenched and worked up in the normal way to afford 2a (65%, 88% ee).
Scheme 3 Hydroalumination–ACA product yields from acyclic enones and for MeAlClCHQCHTMS addition.
the same facial selectivity. Preliminary studies indicate that the scope of the reaction could be partially extended to products 5–7 (in the racemic sense), derived from linear enones (Scheme 3) and via hydroalumination of problematic Me3SiCCH (leading to 8). However, the present conditions do not provide synthetically useful isolable yields – this is under further investigation at present and will be reported later. In conclusion, simple ambient temperature ACA addition to cyclohexenones of terminal alkyne derived ClAlMeCHQCHR gives moderate to good chemical yields in synthetically useful ee values. The latter are readily available from hydroalumination with significantly air stabilised HAlCl2(THF)2.6 SW and DW gratefully acknowledge the Engineering and Physical Sciences (EPSRC; EP/G026882/1) Research Council and the University of Nottingham for funding. SW thanks AA for many fruitful collaborations over the last 20 years and wishes him a diverse and productive retirement.
Notes and references ‡ The structure of the by-product is:
§ The formation of the alternative ‘ate’ species Li[Cl2AlMeCHQCHC6H13] was discounted on the basis of the formation of copious LiCl precipitates. ¶ Representative procedure for the formation of 2a. 1-Octyne was treated with HAlCl2(THF)2 (1.4 equiv.) and Cp*2ZrCl2 (0.05 equiv.) at 80 1C (2 h) in THF followed by solvent removal and the addition of MeLi
This journal is © The Royal Society of Chemistry 2014
1 General overviews of ACA reactions: (a) A. Alexakis, N. Krause and S. Woodward, in Copper Catalysed Asymmetric Synthesis, ed. A. Alexakis, N. Krause and S. Woodward, Wiley-VCH, Weinheim, ¨ller and A. Alexakis, Chem. Com2014, ch. 2, pp. 33–68; (b) D. Mu mun., 2012, 48, 12037; (c) Catalytic Asymmetric Conjugate Reactions, ed. A. Cordova, Wiley-VCH, Weinheim, 2010; (d) S. R. Harutyunyan, T. den Hartog, K. Geurts, A. J. Minnaard and B. L. Feringa, Chem. ¨ckvall, N. Krause, Rev., 2008, 108, 2824; (e) A. Alexakis, J. E. Ba `mies and M. Die ´guez, Chem. Rev., 2008, 108, 2796; O. Pa ´mies and M. Die ´guez, Top. Organomet. Chem., 2013, ( f ) O. Pa 41, 277 and references therein. 2 Rh-catalysed alkenylation (arylation): (a) T. Hayashi and K. Yamasaki, Chem. Rev., 2003, 103, 2829 (overview); (b) T. Hayashi, K. Ueyama, N. Tokunaga and K. J. Yoshida, J. Am. Chem. Soc., 2003, 125, 11508; (c) T. Hayashi, M. Takahashi, Y. Takaya and M. Ogasawara, J. Am. Chem. Soc., 2002, 124, 5052; (d) S. Oi, T. Sato and Y. Inoue, Tetrahedron Lett., 2004, 45, 5051. 3 Cu-catalysed quaternary centre formation: (a) C. Hawner and ¨ller A. Alexakis, Chem. Commun., 2010, 46, 7295 (overview); (b) D. Mu and A. Alexakis, Org. Lett., 2013, 15, 1594; (c) M. Sidera, P. M. C. Roth, R. M. Maksymowicz and S. P. Fletcher, Angew. Chem., Int. Ed., 2013, ¨ller, M. Tissot and A. Alexakis, Org. Lett., 2011, 52, 7995; (d) D. Mu ¨ller and A. Alexakis, Chem.–Eur. J., 2013, 19, 15226. 13, 3040; (e) D. Mu 4 Thermal alkyne hydroalumination: E. Negishi, T. Takahashi and S. Baba, Org. Synth., 1988, 66, 60. 5 Ni-catalysed hydroalumination: K. Akiyama, F. Gao and A. H. Hoveyda, Angew. Chem., Int. Ed., 2010, 49, 419 based on the work of J. J. Eisch and M. W. Foxton, J. Org. Chem., 1971, 36, 3520. 6 P. Andrews, C. M. Latham, M. Magre, D. Willcox and S. Woodward, Chem. Commun., 2013, 49, 1488. 7 With reactive acceptors, e.g. alkylidenemalonates spontaneous additions are observed. 8 A. J. Blake, J. Shannon, J. C. Stephens and S. Woodward, Chem.–Eur. J., 2007, 13, 2462. ¨ller and A. Alexakis, Org. Lett., 2012, 14, 1842. 9 D. Mu 10 Lower 1,4-addition yields from MCHQCHR species attained by hydrometallation are unfortunately not uncommon, for example: see Table 2 in ref. 3d (3 runs o 50%); ref. 9 (5 runs o 50%) ref. 14 (30–70%). See also R. Maksymowicz, P. M. C. Roth, A. Thompson and S. P. Fletcher, Chem. Commun., 2013, 49, 4211. 11 C. Hawner, K. Li, V. Cirriez and A. Alexakis, Angew. Chem., Int. Ed., 2008, 47, 8211. ¨ller, C. Hawner, M. Tissot, L. Palais and A. Alexakis, Synlett, 12 D. Mu 2010, 1694. ¨ller, PhD thesis, University of Geneva, No. Sc. 4502, see 13 D. Mu specifically, p. 110. ¨ller and A. Alexakis, Org. Lett., 2013, 15, 828. 14 P. Cottet, D. Mu 15 J. F. Teichert and B. L. Feringa, Angew. Chem., Int. Ed., 2010, 49, 2486.
Chem. Commun., 2014, 50, 1655--1657 | 1657
