2.3.1. Copper
Copper tolerates the use of non stabilized hard nucleophiles such as non-delocalized carbanions. This reaction has been thoroughly studied and many reviews are dealing with this subject.38 In general, copper-catalyzed allylic substitutions proceed though a SN2’ mechanism (Scheme 2-14), which, contrary to palladium, makes the reaction regiospecific.39 Both Grignard and organo-zinc reagents have been successfully used in this transformation in conjunction with among others enantiopure aminoacids,40 diaminocarbenes,41 diphosphines42 and phosphoramidites43 as ligands.
Cu(I),L
R2 R1
LG
R2 R1
RMgX or R2Zn R
SN2' mechanism
Scheme 2-14: Cu-catalyzed allylation.
36 (a) Bandini, M.; Melloni, A.; Piccinelli, F.; Sinisi, R.; Tommasi, S.; Umani-Ronchi, A. J. Am. Chem. Soc.
2006, 128, 1424-1425. (b) Bandini, M.; Melloni, A.; Tommasi, S.; Umani-Ronchi, A. Synlett 2005, 1199-1222.
(c) Bian, J. W.; Van Wingerden, M.; Ready, J. M. J. Am. Chem. Soc. 2006, 128, 7428-7429. (d) Koch, G.; Pfaltz, A. Tetrahedron: Asymmetry 1996, 7, 2213-2216. (e) Trost, B. M.; Sacchi, K. L.; Schroeder, G. M.; Asakawa, N.
Org. Lett. 2002, 4, 3427-3430.
37 For reviews on the addition of preformed enolates onto π-allyl complexes see: (a) Braun, M.; Meier, T.
Angew. Chem. Int. Ed. 2006, 45, 6952-6955. (b) Braun, M.; Meier, T. Synlett 2006, 661-676.
38 For recent reviews see: (a) Yorimitsu, H.; Oshima, K. Angew. Chem. Int. Ed. 2005, 44, 4435-4439. (b) Kar, A.; Argade, N. P. Synthesis 2005, 2995-3022. (c) Alexakis, A.; Malan, C.; Lea, L.; Tissot-Croset, K.; Polet, D.;
Falciola, C. Chimia 2006, 60, 124-130. (d) Falciola, C.; Alexakis, A. Eur. J. Org. Chem. 2008, 2008, 3755. (e) Alexakis, A.; Bäckvall, J. E.; Krause, N.; Pàmies, O.; Diéguez, M. Chem. Rev. 2008, 108, 2796-2823. (f) Harutyunyan, S. R.; den Hartog, T.; Geurts, K.; Minnaard, A. J.; Feringa, B. L. Chem. Rev. 2008, 108, 2824-2852.
39 The term regiospecificity is not defined in the 1996 IUPAC recommendations.
40 Murphy, K. E.; Hoveyda, A. H. Org. Lett. 2005, 7, 1255-1258.
41 Van Veldhuizen, J. J.; Campbell, J. E.; Giudici, R. E.; Hoveyda, A. H. J. Am. Chem. Soc. 2005, 127, 6877-6882.
42 Geurts, K.; Fletcher, S. P.; Feringa, B. L. J. Am. Chem. Soc. 2006, 128, 15572-15573.
43 Falciola, C. A.; Tissot-Croset, K.; Alexakis, A. Angew. Chem. Int. Ed. 2006, 45, 5995-5998.
2.3.2. Molybdenum
Molybdenum-catalyzed allylic substitutions are very similar to Pd-catalyzed reaction to the key difference that, without any electronic bias, the nucleophile preferentially attacks onto the more substituted terminus of the π-allyl.44 Mechanistic studies have provided conclusive evidence that the Mo-catalyzed allylic alkylations proceeds with an overall retention of configuration through a mechanism involving an oxidative addition and subsequent nucleophilic attack onto the resulting π-allyl complex.44 Many examples have been detailed in the litterature1b,1g,1h and can be exemplified by the following reaction (Scheme 2-15) in which two stereocentres are introduced in a single step.45
10 mol% [Mo(C7H8)(CO)3]
Ar = Ph, 2-thienyl, 2-Br-Ph, 2,4-(MeO)2-Ph
Scheme 2-15: Mo-catalyzed allylic substitution.
2.3.3. Tungsten
The case of tungsten is very similar in terms of selectivity to the one of Mo; notably in this case the tungsten-π-allyl complexes are not subject to anti / syn isomerization and apparent rotation processes contrary to the case for Pd-catalyzed reactions. Mechanistic insight into this reaction has been provided by Kočovský.46 One example is given below (Scheme
Pfaltz, A. Zeit. Naturforsch. 1995, 50b, 361-367.
2.3.4. Rhodium
Rhodium is even less prone to isomerization than tungsten, leading to the possibility to develop regio- and stereospecific reactions.48,1h As shown by A. Evans, the Rh-catalyzed allylic substitution of cinnamyl carbonates with Cu-enolates can be fully regio- and stereospecific (Scheme 2-17).49 Enantioselective versions of this reaction50 have also been developed as shown in Scheme 2-18.51
iii. 5 mol% RhCl(PPh3)3
Scheme 2-17: Regio- and stereospecific Rh-catalyzed allylic substitution.
5 mol% [Rh(dpm)(C2H4)2]
Scheme 2-18: Enantioselective Rh-catalyzed allylic substitution.
2.3.5. Iridium
Ir-catalysts were first probed for allylic substitution by Takeuchi52 and have received the most attention in the context of allylic substitution in the latest years.1g,1h,53 The focus will only be made on carbon-carbon bond forming reactions, for heteroatomic nucleophiles see the above mentioned reviews.1g,1h,52,53 Using [Ir(cod)Cl]2, as precatalyst, fine tuning with ligands and comparison of isomeric substrates uncovered the following trends: (i) reaction rate and regioselectivity are increased by electron-poor ligands and decreased by electron-rich ligands;
(ii) a ligand to Ir ratio of 1 gives optimal results; additional ligand leads to decrease in rate but not in regioselectivity; (iii) the reaction rate is significantly higher for the branched than for the linear substrates; (iv) there are distinct memory effects concerning the allylic substrate in
48Leahy, D. K.; Evans, P. A. In Modern Rhodium-Catalyzed Organic Reactions; ed Evans, P. A., Wiley-VCH:
Weinheim, Germany, 2005, 191-214 and references therein.
49 Evans, P. A.; Leahy, D. K. J. Am. Chem. Soc. 2003, 125, 8974-8975 and references therein.
50 Menard, F.; Chapman, T. M.; Dockendorff, C.; Lautens, M. Org. Lett. 2006, 8, 4569-4572.
51 Hayashi, T.; Okada, A.; Suzuka, T.; Kawatsura, M. Org. Lett. 2003, 5, 1713-1715.
52 (a) Takeuchi, R.; Akiyama, Y. J. Organomet. Chem. 2002, 651, 137-145. (b) Takeuchi, R.; Kashio, M. Angew.
Chem. Int. Ed. Engl. 1997, 36, 263-265. (c) Takeuchi, R.; Kezuka, S. Synthesis 2006, 3349-3366..
53 (a) Helmchen, G.; Dahnz, A.; Dubon, P.; Schelwies, M.; Weihofen, R. Chem. Commun. 2007, 675-691. (b) Miyabe, H.; Takemoto, Y. Synlett 2005, 1641-1655.
that branched substrates give branched products with high selectivity and linear substrates tend to give mixtures; (v) substrates with (Z)-configuration of the double bond preferentially yield linear products with conservation of the (Z)-configuration. A few representative examples of Ir-catalyzed allylation of stabilized carbanions are given in Table 2-5.
Ar
Table 2-5: Examples of allylic alkylation of cinnamyl derived acetates and stereotypical ligands.
The three following examples of Ir-catalyzed allylic substitutions with carbon-carbon bond formation have been chosen due to their strong resemblance with the reaction subsequently
54 Bartels, B.; Helmchen, G. Chem. Commun. 1999, 741-742..
55 (a) Janssen, J. P.; Helmchen, G. Tetrahedron Lett. 1997, 38, 8025-8026. (b) Garcia-Yebra, C.; Janssen, J. P.;
Rominger, F.; Helmchen, G. Organometallics 2004, 23, 5459-5470..
56 (a) Fuji, K.; Kinoshita, N.; Tanaka, K.; Kawabata, T. Chem. Commun. 1999, 2289-2290. (b) Kinoshita, N.;
Marx, K. H.; Tanaka, K.; Tsubaki, K.; Kawabata, T.; Yoshikai, N.; Nakamura, E.; Fuji, K. J. Org. Chem. 2004, 69, 7960-7964.
57 Lipowsky, G.; Miller, N.; Helmchen, G. Angew. Chem. Int. Ed. 2004, 43, 4595-4597.
58 (a) Alexakis, A.; Polet, D. Org. Lett. 2004, 6, 3529-3532. (b) Polet, D.; Alexakis, A.; Tissot-Croset, K.;
Corminboeuf, C.; Ditrich, K. Chem. Eur. J. 2006, 12, 3596-3609. (c) Polet, D.; Alexakis, A. Org. Lett. 2005, 7, 1621-1624.
59 Dahnz, A.; Helmchen, G. Synlett 2006, 697-700.
60 Graening, T.; Hartwig, J. F. J. Am. Chem. Soc. 2005, 127, 17192-17193.
2 mol% [Ir(cod)Cl]2
R = 4-anisyl, 4-CF3-Ph, 2-f uryl,i-Pr,n-Pr,1-propenyl, Ph R' = Ph, 2-anisyl,i-Pr, phenethyl
OBoc R'
OTMS
Scheme 2-19: Ir-catalyzed regio- and enantioselective allylation of preformed silyl enol ethers.
The second example is the Ir-catalyzed allylation of ketamines to give, after acidic hydrolysis, similar γ,δ-unsaturated ketones with high regioselectivity in preference for the branched position and good enantioselectivity (Scheme 2-20).61
i. 2 mol% [Ir(cod)Cl]2
R = Ph, 4-anisyl, 4-CF3-Ph, 2-furyl, 2-anisyl, Me,n-Pr R' = Ph,i-Pr, 2-anisyl,i-Bu
OCO2i-Pr R'
N
Scheme 2-20: Regioselective and enantioselective Ir-catalyzed allylation of preformed enamines.
This last example of Ir-catalyzed allylic substitution deals with the regio- and enantioselective decarboxylative alkylation of γ-substituted allylic β-aryloylacetates in the presence of a stoichiometric amount of base (Scheme 2-21).62 The same reaction, though catalyzed by a Ru-complex, will be the basis for this manuscript.
62-83 % yield
Scheme 2-21: Ir-catalyzed regio- and enantioselective decarboxylative allylic alkylations.
Several other metals have been used as catalysts in allylic substitution such as Ni,63 Pt64 and Fe65 but will not be detailed in this manuscript.
61 Weix, D. J.; Hartwig, J. F. J. Am. Chem. Soc. 2007, 129, 7720-7721.
62 He, H.; Zheng, X. J.; Yi, U.; Dai, L. X.; You, S. L. Org. Lett. 2007, 9, 4339-4341.
63 (a) Consiglio, G.; Piccolo, O.; Roncetti, L.; Morandini, F. Tetrahedron 1986, 42, 2043-2053. (b) Consiglio, G.;
Indolese, A. Organometallics 1991, 10, 3425-3427. (c) Indolese, A. F.; Consiglio, G. Organometallics 1994, 13, 2230-2234. (d) Son, S.; Fu, G. C. J. Am. Chem. Soc. 2008, 130, 2756-2757. (e) Gomez-Bengoa, E.; Heron, N.
M.; Didiuk, M. T.; Luchaco, C. A.; Hoveyda, A. H. J. Am. Chem. Soc. 1998, 120, 7649-7650.
64 (a) Blacker, A. J.; Clarke, M. L.; Loft, M. S.; Mahon, M. F.; Humphries, M. E.; Williams, J. M. J. Chem. Eur.
J. 2000, 6, 353-360. (b) Blacker, A. J.; Clark, M. L.; Loft, M. S.; Williams, J. M. J. Chem. Commun. 1999, 913-914.