Allylation of ketones

As the nitro group is removed by radical denitration with Bu3SnH, allylic alkylation of a-nitro ketones with allyl carbonates in the presence of Pd(0) followed by denitration with Bu3SnH provides a new regio-selective allylation of ketones under neutral conditions (Eq. 5.55).79... 

The oxidation of terminal alkenes to methyl ketones has been extensively applied to syntheses of many natural products [31]. Several 1,4-dicarbonyl compounds are prepared based on this oxidation. Typically, the 1,4-diketone 11 or the 1,4-keto aldehyde 13 can be prepared by the allylation of ketone [18] or aldehyde [32,33], followed by the oxidation. The reaction provides a good annulation method to prepare cyclopentenones 12 and 14. 

Jorgensen et al. reported that C2-symmetric bis(oxazoline)-copper(II) complex 25 also acts as chiral Lewis acid catalyst for a reaction of allylic stannane with ethyl glyoxylate [37]. Meanwhile, p-Tol-BINAP-CuCl complex 26 was shown to be a promising chiral catalyst for a catalytic enantioselective allylation of ketones with allyltrimethoxysilane under the influence of the TBAT catalyst [38]. Evans and coworkers have developed (S,S)-Ph-pybox-Sc(OTf)3 complex 27 as a new chiral Lewis acid catalyst and shown that this scandium catalyst promotes enantioselective addition reactions of allenyltrimethylsilanes to ethyl glyoxylate [39]. But, when the silicon substituents become bulkier, nonracemic dihydrofurans are predominantly obtained as products of [3+2] cycloaddition. 

Oxocarbenium ions bearing a chiral auxiliary are useful for asymmetric allylation with 10. For example, oxocarbenium ions generated from aldehydes and homochiral Me3Si ether 15 are allylated with high diastereoselectivity (Scheme 104,104a,104b rp e resultant homoallyl ethers can easily be converted into homoallyl alcohols without epimerization. This two-step procedure is applicable to enantioselective allylation of ketones.105,1053... 

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 ... 

Tietze et al. emphasized the usefulness of chiral trimethylsilyl ethers of readily accessible amino alcohol derivatives in allylation of aldehydes and ketones [43]. As a consequence, careful design of the norpseudoephedrine derivatives and proper choice of silicon Lewis acids have led to the convergent preparation of enantiomerically enriched secondary and tertiary homoallylic alcohols in high yields (Sch. 12) [43a], It should be noted that the configuration of the newly formed stereogenic center of the secondary homoallylic alcohols is the opposite of that in the allylation of ketones [43c], They also described in detail mechanistic studies of the above allylation reaction by use of and NMR. 

Kii, S., Maruoka, K. Catalytic enantioselective allylation of ketones with novel chiral bis-titanium(IV) catalyst. Chirality 2003,15, 68-70. 

Allylation of ketones is a fundamental and important transformation, and therefore, efficient catalysts promoting addition of allylstannanes to ketones have been investigated [89]. Enantioselective allylation of ketones is a very challenging topic. It has been disclosed that asymmetric allylation of ketones with allylstannanes was promoted by addition of BINOL/TiCl2(OiPr)2 catalyst [90] or by premixing of BINOL with tetraallyltin [91]. In these reactions, however, enantioselectivity was not sufficient for practical purposes (acetophenone <65% ee). It was recently discovered that acetophenone was allylated by a mixture of tetraallyltin and an alkyl-triallyltin in the presence of monothiobinaphthol to furnish the desired chiral homoallyl alcohol with high enantioselectivity (Scheme 12.35) [92]. 

Allyltin compounds were uniformly shown to be less reactive than the zinc or especially indium analogs. Thus, strongly acidic conditions (HBr, AcOH) were required to perform the heterogeneous reaction using metallic tin, allylic bromides and aldehydes, even if the presence of water accelerated the reaction compared to the reaction in pure diethyl ether. Allylation of ketones required metallic aluminum as an additive [115]. In this way, five- or six-membered rings were prepared through intramolecular reactions (Scheme 24) [116]. 

This reaction is part of a useful cyclopentannelation sequence. Allylation of ketones is among the easiest alkylations subsequent Wacker oxidation and cyclisation creates anew five-membered ring 76. This is the a-acyl cation strategy discussed in chapter 6, though this version of it was not mentioned. 

Sulfoxides and sulfonium ylids Regio- and stereochemical control [2,3] Sigmatropic shifts in the allylation of ketones Recent applications... 

The allylation of ketones is a simple reaction. Most of the specific enol equivalents described in chapters 2-6 react well with allylic halides. Disconnection of the y,5-unsaturated ketone 59 to the enolate 61 and the allylic halide 60 is trivial and the reaction of, say, an enamine will occur at the less hindered primary centre to give 59. However, supposing the target molecule is the isomeric ketone 63. The same disconnection gives the isomeric allylic bromide 62 which will almost certainly give the alternative product 59 by reaction at the less hindered end of the alkene. 

AUylation. The multidentate ligand 9 has been developed for regioselective and diasteieoselective allylation of ketones. ... 

The alkylation of a-hetero substituted aldehydes and ketones is often a far from simple process. However methods for both the a and a -alkylation of fluoroacetone by way of its lithium N-cyclohexyl enamide,1 0 and the alkylation of formamido ketones1 1 have been reported. The allylation of ketones has received a... 

Allylation of ketone enolates is treated in Chapter 4.2.3. The chemistry of tt-allylpalladium enolates, which is related, but more versatile than that of simple ketone enolates, is treated in this section. 7r-Allylpalladium enolates are generated in two ways. One is the transmetallation of silyl and tin enolates with TT-allylpalladium alkoxide formed from allyl carbonates. The other is Pd-catalyzed reaction of allyl j6-keto esters [199]. 

Scheme 7.38 Enantioselective allylation of ketone 64 using pol5maer-supported BINOL ligand 66.

SCHEME 8.33. An example of asymmetric a-allylation of ketones reported by MacMillan and co-workers [140]. 

Mastracchio A, Warkentin AA, Walji AM, MacMillan DWC (2010) Direct and Enantioselective a-Allylation of Ketones via Singly Occupied Molecular Orbital (SOMO)... 

Scheme 12.47 Pd-catalyzed a-allylation of ketones with allyl alcohols involving proline activation [109dj.

The allylation of ketones and aldehydes was accomplished by Yamamoto, where preformation of TMSNTf2 was done in diethyl ether at —78°C for 15 min. Slow addition of the carbonyl compound followed by acidic hydrolysis gave the allylation products in high yield (eq 6). 

No allylation of simple ketones, aldehydes, and esters without additional EWGs occurs. Allylation of ketones is carried out indirectly. For example, enamines, prepared from ketones, are allylated easily and allyl ketones are obtained after hydrolysis (Scheme... 

In summary, the Pd-catalyzed a-allylation of ketones can be achieved with the corresponding enolates containing Li, Li + 2BEt3, ZnX, BEtsK, SiMcs, and SnRs as the metal countercations. In some demanding cases, however, the most satisfactory results may be obtained through the use of Li + 2 BEts, ZnX, or BEtsK as the countercation. 

Intermediacy of Tr-allylpalladium(ll) enolate is proposed for /3-elimination of palladium hydride, which leads to the formation of a,/S-unsaturated ketones. Competitive allylation of ketones is favored by use of palladium(0)(dba)2 (dba dibenzylideneacetone) in THF. 

Vitamin E (a) L. F. Tietze, J. Gorlitzer, A. Schuffenhauer, M. HUbner, Eur. J. Org. Chem. 1999, 1075-1084. Enantioselective synthesis of the chromane moiety of vitamin E. (b) L. F. Tietze, J. Gorlitzer, Synlett 1997, 1049-1050. Preparation of enantiopure precursors for the vitamin E synthesis. A comparison of the asymmetric allylation of ketones and the sharpless bishydroxylation. (+)-Hydroxymyoporone (c) L. F. Tietze, C. Wegner, C. Wulff, Chem.-Eur. J. 1999, 5, 2885-2889. First total synthesis and determination of the absolute configuration of the stress factor (+)-hydroxymyoporone. 5,6-Dihydrocineromycin B (d) L. F. Tietze, L. Vblkel, Angew. Chem. Int. Ed. 2001, 40, 901-902. Total synthesis of the macrolide antibiotic 5,6-dihydrocineromycin B. 

Type of reaction C-C bond formation Reaction conditions Solvent-free, room temperature Synthetic strategy One-step allylation of ketones Catalyst Zinc-copper couple... 

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