Stoichiometric Allylation of Aldehydes and Ketones

As discussed above, catalytic allylation with AUylSiCh is generally confined to conjugated aldehydes (aromatic, heteroaromatic, and dnnamyl). However, if a 

Stoichiometric activator is employed, for example, DMF or HMPA, as an additive or solvent the substrate range broadens to aliphatic aldehydes and a-keto acids RCOCO2H (R = aryl, alkyl) [16]. In the case of chiral aldehydes, such as N-protected alaninal, diastereoselectivity attained in DMF is modest ( 3 1) [54]. AllylSiFs can transfer the allyl group to a-hydroxy ketones and (l-diketones on heating with EtsN in THF [55]. 

Allylation of hydrazones derived from aryl alkyl ketones [56] and of N-aryl aldi-mines in DMF at 0°C [61] has also been reported. 

Aldimines react with AllylSiMe3 (2a) in the presence of iodine in MeCN to afford the products of allylation but an asymmetric version of this method has not yet been developed [62]. Nevertheless, with a chiral auxiliary attached to the imine nitrogen, dual catalysis was reported here, In(lll) was employed as a Lewis acid to coordinate the imine nitrogen, while BujN F was used as a Lewis basic activator of the Si, resulting in excellent diastereocontrol [63, 64]. 

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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. 

Several methods promoted by a stoichiometric amount of chiral Lewis acid 38 [51] or chiral Lewis bases 39 [52, 53] and 40 [53] have been developed for enantioselective indium-mediated allylation of aldehydes and ketones by the Loh group. A combination of a chiral trimethylsilyl ether derived from norpseu-doephedrine and allyltrimethylsilane is also convenient for synthesis of enan-tiopure homoallylic alcohols from ketones [54,55]. Asymmetric carbonyl addition by chirally modified allylic metal reagents, to which chiral auxiliaries are covalently bonded, is also an efficient method to obtain enantiomerically enriched homoallylic alcohols and various excellent chiral allylating agents have been developed for example, (lS,2S)-pseudoephedrine- and (lF,2F)-cyclohex-ane-1,2-diamine-derived allylsilanes [56], polymer-supported chiral allylboron reagents [57], and a bisoxazoline-modified chiral allylzinc reagent [58]. An al-lyl transfer reaction from a chiral crotyl donor opened a way to highly enantioselective and a-selective crotylation of aldehydes [59-62]. Enzymatic routes to enantioselective allylation of carbonyl compounds have still not appeared. 

In the pioneering works by Hosomi and Sakurai, a stoichiometric or substoichio-metric amount of TiCU, a conventional Lewis acid, was used for the carbonyl allylation with allylsilanes [106]. Davis and coworkers found that TMS borates such as Me3Si[BX(OTf)3] (X = OTf, Cl) enables an efficient, catalytic Hosomi-Sakurai allylation of aldehydes although (la) and Me3SiI show low catalytic activities (Scheme 9.41) [18, 107]. Ishihara and Yamamoto have demonstrated the utility of (lb) as Lewis acid catalyst of the carbonyl allylation as well as the Mukaiyama aldol reaction [15]. The silicon Lewis acid (lb), generated in situ by the reaction of allyltrimethylsilane with HNTf2, efficiently promotes the allylation of aldehydes and ketones with a loading of 0.5 mol% (Scheme 9.41). 

The Barhier-type reaction of aldehydes and ketones with allyl halides (485) in the presence of Sml2, leading to homoallyl alcohols (486), has received recent interest as a one-step alternative to the Grignard reaction. However, the reactions require the use of stoichiometric amounts of the reducing Sm(III) species. Recently, the electroreductive Barhier-type allylation of carbonyl compounds in an SmH-mediated reaction has been developed [569]. The electrolysis of (485) is carried out in a DMF-SmCl3-(Mg/Ni) system in an undivided cell to give the adduct (486) in 50 85% yields (Scheme 168) [569]. Electrosynthesis of y-butyrolactones has been achieved by the reductive coupling of ethyl 3-chloropropionate with carbonyl compounds in the presence of a catalytic amount of SmCfi [570]. 

Tamaru reported that Pd-catalyzed a-allyladon of aldehydes to afford 168 can be carried out even with allyl alcohols in the presence of a stoichiometric amount of EtaB, NEt3, and LiCl. Although the mechanism is not clear, activation of allyl alcohol by Et3B occurs by coordination to generate 7r-allylpalladium. In addition, boron enolates are formed by the reaction of aldehydes with Et3B and Et3N, and attacked by r-allylpalladium [62]. Similarly allylation of malonates and ketones with allylic alcohols 169 and 169a were carried out [63],... 

Through the use of Inis, Baba et al. had managed to dispense with TMSCI to regenerate the catalyst [30]. Only 10 to 20 mol% of Inis was required for the allylation of aldehydes and aromatic ketones with allyltributyltin, and stoichiometric amounts of Inis was found to inhibit the reaction. Reaction was expected to proceed via an entirely transmetallation pathway owing to the lower Lewis acidity of Inis. Thus, for y-substituted allylic tin compounds, typical anti preference for the addition product was observed. A chelation-controlled addition was used to explain the rate acceleration and higher yields of carbonyl compounds with vicinal alkoxy group, and the predominance of the syn addition product for such compounds (Figure 8.12). 

Carbanions, generated by the reaction of benzylsilanes with tetra-n-butylammo-nium fluoride react with non-enolizable aldehydes to produce the alcohol [67], When a stoichiometric amount of the ammonium fluoride is used, the methylarene corresponding to the benzylsilane is frequently a by-product and arises from formation of the hydrogen difluoride salt during the reaction. When only catalytic amounts of the ammonium fluoride initiate the reaction, the formation of the methylarene is suppressed. In a similar type of reaction (although the mechanism is not known) between aldehydes and ketones, allyl bromide, and tin in the presence of trimethylsilyl chloride the yield of the but-l-en-4-ol is raised significantly by the addition of tetra-n-butylammonium bromide, particularly in the reactions with... 

Despite their obvious economical and ecological importance, few catalytic systems are available for the transformation of alcohols into aldehydes and ketones, using molecular oxygen or air as the ultimate, stoichiometric oxidant (5). Moreover, most of the currently available catalytic oxidation processes suffer from severe limitations, being usually only effective with reactive alcohols, such as benzylic and allylic ones, or requiring high pressures, temperatures, and catalyst loading. 

The pioneering works by Flosomi and Sakurai described that conventional Lewis acids (TiCLt, S11CI4, and BFj OEtd are effective in the allylation of aldehydes, ketones, and acetals with a (sub)stoichiometric quantity.72... 

Lithium aminoborohydrides are obtained by the reaction of -BuLi with amine-boranes [FF2, FH5, NT2]. They can be generated in situ as THF solutions or as solids when formed in diethylether or hexane (n-BuLi must then be used in sub-stoichiometric amounts). They are stable under dry air and are slowly decomposed by water [NT2] or methanol so that workup of the reactions mixtures can be carried out with 3M HCl. They reduce alkyl halides (Section 2.1), epoxides (Section 2.3), aldehydes, and ketones (Section 3.2.1) (in the latter case with an interesting stereoselectivity [HFl]), and esters to primary alcohols (Section 3.2.5). a,(3-Unsaturated aldehydes, ketones, and esters are reduced to allyl alcohols (Section 3.2.9) [FF2, FS2]. Depending on the bulkiness of the amines associated with the reagent and to the substrate, tertiary amides give amines or alcohols (Section 3.2.8) [FFl, FF2]. Amines are also formed from imines (Section 3.3.1) [FB1 ] and from azides (Section 5.2) [AFl]. However, carboxylic acids remain untouched. 

Alcohols, particularly benzylic and allylic ones, are oxidized to aldehydes and ketones under PTC conditions. Both stoichiometric and catalytic processes have been performed As in the case of permanganate, the reaction is controlled by pH in... 

Reduction of conjugated carbonyl compounds using stoichiometric amounts of the ammonium salt shows little advantage over the sodium salt in acidic methanol [11] with both reagents producing allylic alcohols (58-88% for acyclic compounds and 15-64% for cyclic compounds) by selective 1,2-reduction of the conjugated systems. Aldehydes, ketones and conjugated enones are also reduced by tetra-n-butylammonium cyanoborohydride in HMPA [11, 12], whereas haloalkanes and alkanesulphonic esters are cleaved reductively under similar conditions [13]. 

Abstract The purpose of this chapter is to present a survey of the organometallic chemistry and catalysis of rhodium and iridium related to the oxidation of organic substrates that has been developed over the last 5 years, placing special emphasis on reactions or processes involving environmentally friendly oxidants. Iridium-based catalysts appear to be promising candidates for the oxidation of alcohols to aldehydes/ketones as products or as intermediates for heterocyclic compounds or domino reactions. Rhodium complexes seem to be more appropriate for the oxygenation of alkenes. In addition to catalytic allylic and benzylic oxidation of alkenes, recent advances in vinylic oxygenations have been focused on stoichiometric reactions. This review offers an overview of these reactions... 

An extremely useful alternative method, employing catalytic amounts of Pd° complexes, rather than stoichiometric (or near stoichiometric) quantities of Pd11 salts has been developed. The oxa-tr-allyl complex is accessed via allyl p-ketocarboxylates360-363 or allyl alkenylcarbonates360,361,363,364 in the intramolecular cases and via enol acetates,361,363,365 enol silyl ethers361,366 or ketene silyl acetals367 with allyl carbonates in the intermolecular cases. The products of these reactions are the corresponding a,p-un-saturated ketones, aldehydes and esters (equations 138-142). 

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