Catalytic Allylation of Aldehydes

Fluoride ion (from CsF, CdF2, or AgF) can also catalyze the allylation using AllylSiFs and AUylSi(OMe)3, respectively [10, 11] the asymmetric version (with 56% ee) requires a combination of Bu4N [SiPh3F2] with the Lewis acidic complex of CuCl and BINAP [21]. While aldehydes react readily, ketones are normally inert under the catalytic conditions. 

Chiral formamide 13 (figure 15.1) typically requires 20mol% loading and HMPA (1 equiv) as a co-catalyst to attain 80% yield and 98% ee, the reaction was left at -78 °C for 2 weeks, which is less than practical. Interestingly, 13 is the only catalyst reported to date that exhibits very high enantioselectivities ( 98% ee) with aliphatic aldehydes, while with benzaldehydes it gives an almost racemic product (8% ee) [17]. 

Prior to Hayashi s report [26], Maikov and Kocovsk [27] found the terpene-derived bipyridine N-monoxides 19-21 (PINDOX, Me2PlNDOX, and iso-PINDOX) to be even more enantioselective than Nakajima s N,N -dioxide 17, 

Other pyridine-type N-monoxides, namely, 23 (QUINOX) [30], 24 (the first nonpyridine-type N-oxide) and its congeners [31], and the pyridine N-oxide 25 [32] have also been reported as successful organocatalysts. This series is complemented by the N,N -dioxide 26 (with 96% ee), its atropoisomer and their congeners [36, 37], the N,N, N -trioxide 27 and its analogues [33], and the related bis-imidazole N,N -dioxides [38]. 

Other pyridine-type N-oxides with various scaffolds (terpene [40], carbohydrate [41], etc. [42, 43]) have also been reported but as a rule their enantioselectivities do not exceeds those discussed above. A notable exception has been reported for 

METHOX (22) was synthesized in three steps from the commercially available pinocarvone (47) using the Krohnke annulation (47 + 48 — 50). Pinocarvone itself, commercially available only in one enantiomeric form, can be readily obtained from the much cheaper a-pinene (46) via an ene-reaction with singlet oxygen. Since both enantiomers of a-pinene are commercially available, this procedure can be utiUzed for the preparation of both enantiomers of METHOX (22) (28b). The Krohnke reagent 48 [52] is readily obtained in one pot via iodination of the corresponding acetophenone (49) in pyridine (28b). 

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The allylation of aldehydes can be carried out using stannous chloride and catalytic cupric chloride or copper in aqueous media." In-situ probing provides indirect (NMR, CV) and direct (MS) evidence for the copper(I)-catalyzed formation of an allyltrihalostannane intermediate in very high concentration in water (Scheme 8.6). Hydrophilic palladium complex also efficiently catalyzes the allylation of carbonyl compounds with allyl chlorides or allyl alcohols with SnCl2 under aqueous-organic... 

Later, Araki et al. found that the allylation of aldehydes and ketones can be carried out by using catalytic amounts of indium(III) chloride in combination with aluminum or zinc metal.109 This reaction was typically performed in a THF-water (5 2) mixture at room temperature, although the conversion was much slower compared to the same reaction mediated by use of a stoichiometric amount of indium and it required days to complete. When the reaction was carried out in anhydrous THF alone, the yield dropped considerably and side-reactions such as reduction to alcohol increased. The combinations of Al-InCL or Zn-InCl3 gave comparable results. 

Intermolecular allylation of aldehydes with 1 -trialkylsilyl-1,3-dienes 22 in the presence of a stoichiometric amount of triethylsilane and a catalytic amount of Ni(cod)2 and PPI13 shows novel regio- and stereoselectivity (Scheme 6) [20-22], When a toluene solution of a 1-silyl-1,3-diene and an aldehyde is refluxed in the presence of trialkylsilane under the catalysis of Ni(cod)2 and PPh3, ( )-allylsilane (E)-23 is obtained exclusively. On the other hand, when the reaction is carried out in THF upon heating at 50 °C as... 

Because of lack of catalytic processes for metals such as Sb and Bi (except for a few cases) [530, 532], recycling of the metals in multimediatory redox systems is of current interest. Recently, allylation of aldehydes (499) with (500) has been performed in an aqueous CH2Cl2-BiCl3-(Pt) two-phase system. Although the reaction (499— 501) can proceed in neutral solution, the best result is obtained in acidic media (Scheme 174) [577]. 

A chiral dinuclear Ti(IV) oxide 20 has been successfully designed by Maruoka and coworkers and can be used for the strong activation of aldehydes, thereby allowing a new catalytic enantioselective allylation of aldehydes with allyltributyltin (Scheme 12.18). ° The chiral catalyst 20 can be readily prepared either by treatment of bis(triisopropoxy)titanium oxide [(/-Pr0)3Ti-0-Ti(0/-Pr)3] with (S)-BINOL or by the reaction of ((5)-binaphthoxy)isopropoxytitanium chloride with silver(I) oxide. The reaction of 3-phenylpropanal with allyltributyltin (1.1 equiv) under the influence of 20 (10 mol%) gives l-phenyl-5-hexen-3-ol... 

The concept of CPTC has been applied in a large number of catalytic reactions such as reduction of allyl chlorides with HCOONa, carbonylation of aryl and allyl halides, allylation of aldehydes, cyanation of aryl halides etc.214 For example, Okano et a/.215 reduced l-chloro-2-nonene to afford 1-nonene and... 

Catalytic asymmetric allylations of aldehydes or ketones are roughly classified into two methods, namely, those using chiral Lewis acid catalysts and those using chiral Lewis base catalysts. The former method uses less reactive allylsilanes or allylstannanes as the allyl source. The latter method requires allyltrichlorosi-lane or more reactive allylmetals. Both processes are applicable to the reactions with substituted allylmetal compounds or propargylation. 

A similar chiral silver(I) catalyst 21 was applied to the asymmetric addition of allyltributyltin to various aldehydes in an aqueous medium [28]. Shi et al. have shown that chiral silver complex 22, prepared from chiral bidentate phospho-ramide and AgOTf, is also an effective chiral catalyst for the allylation [29]. Chiral bis(oxazoline) ligands have found widespread use in asymmetric reactions catalyzed by chiral metal complexes, and C2-symmetric chiral bis(oxazoline)-Zn(OTf)2 complex 23 has been applied to catalytic enantioselective allylation of aldehydes with allyltributyltin (44) however, satisfactory enantioselectivity was not observed [30]. 

Many noticeable examples of chiral Lewis base catalyzed allylation of carbonyl compounds have also appeared. Iseki and coworkers published a full paper on enantioselective addition of allyl- and crotyltrichlorosilanes to aliphatic aldehydes catalyzed by a chiral formamide 28 in the presence of HMPA as an additive [41]. This method was further applied to asymmetric allenylation of aliphatic aldehydes with propargyltrichlorosilane [40]. Nakajima and Hashi-moto have demonstrated the effectiveness of (S)-3,3 -dimethyl-2,2 -biquinoline N,AT-dioxide (29) as a chiral Lewis base catalyst for the allylation of aldehydes [42]. In the reaction of (fs)-enriched crotyltrichlorosilane (54 , E Z=97 3) with benzaldehyde (48), y-allylated anfi-homoallylic alcohol 55 was obtained exclusively with high ee while the corresponding syn-adduct was formed from its Z isomer 54Z (fs Z= 1 99) (Scheme 6). Catalytic amounts of chiral urea 30 also promote the asymmetric reaction in the presence of a silver(I) salt, although the enantioselectivity is low [43]. 

Catalytic asymmetric allylation of aldehydes and ketones with allylsilanes can be achieved by using chiral Lewis acids, transition metal complexes, and Lewis bases. In recent years, much attention has been paid for the chiral Lewis base-catalyzed system using allyltrichlorosilanes. Advances in catalytic asymmetric carbonyl allylation have been described in detail in recent reviews.116,117,117a... 

Practical and efficient asymmetric allylation of aldehydes is successfully promoted by Lewis acid catalysts bearing chiral auxiliaries to afford high levels of enantioselectivity.165 The effective catalysts for asymmetric allylation to benzaldehyde are shown below (Scheme j) 166-176 The catalytic asymmetric allylation of ketones has proved to be a more challenging transformation owing to the significantly low reactivity compared to aldehydes. In 2002, a catalyst based on titanium complex was developed (Equation (51)).A ... 

As a conceptually new allylation of aldehydes, an allylic functionality of the homoallyl alcohols is transferred to aldehydes via the formation of a hemiacetal and the elimination of acetone to give a-adduct homoallylic alcohols in the presence of a catalytic amount of Sn(OTf)2 (Equation (107)).274... 

Aldehydes, ketones, and acetals react with allyltrimethylsilane in the presence of a catalytic amount of BiX3 (X = C1, Br, OTf) to give homoallyl alcohols or homoallyl alkyl ethers (Equation (52)).91-93 The BiX3-catalyzed allylation of aldehydes and sequential intramolecular etherification of the resulting homoallylic silyl ethers are involved in the stereoselective synthesis of polysubstituted tetrahydropyrans (Equation (53)).94,95 Similarly, these Lewis acids catalyze the cyanation of aldehydes and ketones with cyanotrimethylsilane. When a chiral bismuth(m) catalyst is used in the cyanation, cyanohydrines are obtained in up to 72% ee (Equation (54)). a-Aminonitriles are prepared directly from aldehydes, amines, and cyanotrimethysilane by the BiCl3-catalyzed Strecker-type reaction. 

In indium-mediated reactions, a catalytic use of expensive indium is desirable from an economical standpoint, and it has been achieved in combination with more electron-positive metals. Thus, allylation of aldehydes and ketones, as well as prenylation of 2-chlorobenzoquinone, has been performed by using metallic aluminum or zinc in combination with a catalytic amount of indium(m) chloride.63 Also, allylation of aldehydes and ketones with allyl bromide is carried out with a catalytic amount of indium powder (from 0.01 to 0.1 equiv.) in THF in the presence of manganese and chlorotrimethylsilane as the reducing and oxophilic agents, respectively (Scheme 2). 64,65... 

Miscellaneous. There are several other reports on the application of this ligand to catalytic asymmetric reactions, although enantioselectivities are modest. Those reports include the Mukaiyama-Michael reaction, allylation of aldehydes, asymmetric Diels-Alder reaction, Mukaiyama-Aldol reaction of ketomalonate, aziridination reaction of a-imino esters, and asymmetric hetero-Diels-Alder reaction. ... 

Allylation of Aldehydes. Synthesis of enantiomerically pure allyl alcohols can be accomplished by catalytic asymmetric addition of divinylzinc to aldehydes using a camphorsulfonic acid-derived catalyst (eq 22). ... 

Yu, C.-M., Choi, H.-S., Jung, W.-H., Lee, S.-S. Catalytic asymmetric allylation of aldehydes with BINOL-Ti(IV) complex accelerated by I-PrSSiMes. Tetrahedron Lett. 1996, 37, 7095-7098. 

Brenna, E., Scaramelli, L., Serra, S. An efficient atropisomeric chiral biaryl ligand for catalytic stereoselective allylation of aldehydes a novel approach to 2,2 -binol analogs. Synlett 2000, 357-358. 

Kii, S., Maruoka, K. Practical approach for catalytic asymmetric allylation of aldehydes with a chiral bidentate titanium(IV) complex. Tetrahedron Lett. 2001,42,1935-1939. 

Palladium(0)-catalyzed a-allylations of TMS enol ethers can be carried out cleanly with allylic carbonates. These reactions are highly regioselective, e.g. the mtne- and less-substituted TMS enol derivative of 2-methylcyclohexanone cf. Scheme 37) gave 2-allyl-2-methylcyclohexanone and 2-methyl-6-allylcyclohexanone, respectively. Allylations of aldehyde silyl enol ers occur similarly. Allylations of enol acetates occur with allyl carbonates in the presence of catalytic amounts of palla-dium(0) complexes and tri-n-butyltin methoxide. ... 

There are very few examples of Lewis base-promoted allylations of aldehydes with allylstannanes. In 1992 Baba disclosed an intriguing method for allylation of aldehydes with allyl- and 2-butenyltributylstannanes in the presence of catalytic-amounts of dibutyltin dichloride and certain coactivators such as tetrabutylammo-nium iodide, tributylphosphine oxide, HMPA or tetraphenylphosphonium iodide [76]. No definitive mechanistic information is available on the role of the co-activators the authors speculate that the ligands accelerate the metathesis to form allyldibutyltin chloride which is the actual nucleophile. The same group has recently reported the use of a lead(II) iodide/HMPA catalyst for the allylation of a,yff-epoxyketones [76bj. 

For benzoic acid acceleration in Yb(OTf)3-catalyzed allylation of aldehydes in acetonitrile, (a) As-pinall, H.C. Greeves, N. Mclver, E. G. Tetrahedron Lett. 1998, 39, 9283. For acetic acid acceleration in Yb(fod)3-catalyzed ene reaction of aldehydes with alkyl vinyl ethers, ene reaction of aldehydes with alkyl vinyl ethers, (b) Deaton, M. V. Ciufolini, M.A. Tetrahedron Lett. 1993, 34, 2409. Yamamoto et al. reported Brpnsted acid-assisted chiral Lewis acids and Lewis acid-assisted Brpnsted acids which were used for catalytic asymmetric Diels-Alder reactions and protonations and stoichiometric asymmetric aza Diels-Alder reactions, aldol-type reactions of imines, and an aldol reaction, (c) Ishihara, K. Yamamoto, H. J. Am. Chem. Soc. 1994, 116, 1561. (d) Ishihara, K. Kurihara, H. Yamamoto, H. J. Am. Chem. Soc. 1996, 118, 3049. (e) Ishihara, K. Nakamura, S. Kaneeda, M. Yamamoto, H. J. Am. Chem. Soc. 1996, 118, 12854. (f) Ishihara, K. Miyata, M. Hattori, K. Tada, T. Yamamoto, H. J. Am. Chem. Sc c. 1994, 116, 10520. (g) Yamamoto, H. J. Am. Chem. Soc 1994, 116, 10520. (h) ishihara, K. Kurihara, H. Matsumoto, M. Yamamoto Ishihara, K. Kurihara, H. Matsumoto, M. Yamamoto, H. J. Am. Chem. Soc 1998, 120, 6920. 

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