Aldehydes enantioselective allylation

As practiced in the preceding syntheses by Evans and Nishiyama and Yamamura, the A-ring fragment 43 is formed through substrate-directed vinylogous aldol reaction of the Brassard-type diene 19 and the chiral aldehyde 42, which is prepared using Brown s protocols for enantioselective allylation [53], followed by hydroxy-directed nnn-diastereoselective reduction of the C3 ketone (Me4NB(OAc)3H) [41],... 

Allylation of aromatic aldehydes with allyl trimethylsilane catalyzed by chiral acyloxyborane gives good results. In contrast, the results are normally poor for aliphatic aldehydes.89 Costa et al.90 introduced another enantioselective allylation procedure aiming to overcome this problem. In the following example, the enantioselective allylation of aldehyde octanal was carried out using... 

Scheme 13.19. Enantioselective allyltitanation of aldehydes with allyl TiCp(ODAG)2...

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... 

H. Yamamoto reported an enantioselective allylation of aldehydes catalyzed by AgF-p-tol-BINAP complex, [Eq. (13.24)]. High enantioselectivity was obtained... 

Another type of Cinchona alkaloid catalyzed reactions that employs azodicarbo-xylates includes enantioselective allylic amination. Jprgensen [51-53] investigated the enantioselective electrophilic addition to aUyhc C-H bonds activated by a chiral Brpnsted base. Using Cinchona alkaloids, the first enantioselective, metal-free aUyhc amination was reported using alkylidene cyanoacetates with dialkyl azodi-carboxylates (Scheme 12). The product was further functionalized and used in subsequent tandem reactions to generate useful chiral building blocks (52, 53). Subsequent work was applied to other types of allylic nitriles in the addition to a,P-unsaturated aldehydes and P-substituted nitro-olefins (Scheme 13). 

In addition, Iseki et al. reported a highly enantioselective allylation reaction with ahphatic and unconjugated aldehydes. They used chiral DMF derivatives and observed a dramatic increase in the yield and enantioselectivity of the reaction, when a stoichiometric amount of HMPA was employed [57, 58]. 

Next to P(0) or N(0) Lewis bases, there are very rare cases where enantiopure sulfoxides are used in combination with silanes. Kobayashi and coworkers reported a highly diastereoselective and enantioselective allylation of hydrazones with chiral sulfoxide 32 (Scheme 23) [76], Massa [77,78] and Bamess [79] reported the asymmetric allylation of aldehydes with enantiopure sulfoxides, respectively, with moderate selectivity. 

In 1998, Yamamoto et al. reported the first catalytic enantioselective allylation of imines with allyltributylstannane in the presence of a chiral 7i-allylpalladium complex 23 (Scheme 9) [15]. The imines derived from aromatic aldehydes underwent the allylation with high ee values. Unfortunately, the allylation reaction of aliphatic imines resulted in modest enantioselectivities. They proposed that a bis-Jt-allylpalladium complex is a reactive intermediate for the allylation and reacts with imines as a nucleophile. The bis-Jt-allylpalladium complex seemed the most likely candidate for the Stille coupling [16]. Indeed, the Stille coupling reaction takes place in the presence of triphenylphosphine even if imines are present, whereas the allylation of imines occurs in the absence of the phosphine [17]. They suggested the phosphine ligand played a key role in controlling the... 

Keck reported an asymmetric allylation with a catalytic amount of chiral titanium catalyst [24]. The enantioselective addition of methallylstannane to aldehydes is promoted by a chiral catalyst 13 prepared from chiral BINOL and Ti(0-i-Pr)4 (Scheme 9.10). An example of asymmetric amplification was reported by using (R)-BINOL of 50% ee, and the degree of asymmetric amplification was dependent on the reaction temperature. Tagliavini also observed an asymmetric amplification in the enantioselective allylation with a BIN0L-Zr(0-i-Pr)2 catalyst [25]. 

S)-Prolinc-dcrivcd phosphoramides catalyse enantioselective allylation of aromatic aldehydes with allylic trichlorosilanes.90 Chiral a-aminoaldehydes have been allylated diastereoselectively with various reagents.91... 

Advantages of Brown s chiral allylboranes (isopinocampheyl and later caranyl borane) are the easy access to the ligands (a-pinene is a natural product, chiral pool), the availability of both enantiomers and their low price. Excellent selectivities (96-99% ee) can be obtained at reaction temperatures of -100 °C. Other important mediators for enantioselective allylation of aldehydes are shown below.14... 

An allylboronate derivative of tartaric acid developed for enantioselective allylation of aldehydes is readily recyclable without losing selectivity.182... 

A proline-derived /V-oxidc catalyses enantioselective allylation of aldehydes, using allyltrichlorosilane at ambient temperature.188 >>... 

Chiral BINOL-indium(ni) complexes have been employed in several enantioselective allylations (i) in the ionic liquid, hexylmethylimidazolium-PF6, for aldehydes,190 (ii) a moisture tolerant version, for a wide variety of aldehyde types,191 and (iii) a recyclable example, useful for aromatic, aliphatic, and a,/S-unsaturated ketones.192... 

In 2000, Loh and coworkers reported the enantioselective allylation reaction in the presence of AgN03-Tol-BINAP in an aqueous medium (Scheme 9.2).6 They surveyed the reaction media and found that a 1 9 mixture of water ethanol was optimal. The reaction of allyltributyltin and aldehyde in the presence of AgN03-Tol-BINAP in water and ethanol gave the corresponding homoallyl alcohols with moderate to good enantioselectivities. 

Chiral (acyloxy)borane (CAB) is known as an effective chiral Lewis acid catalyst for enantioselective allylation of aldehydes. Marshall applied the CAB complex 1 to the addition of crotylstannane to achiral aldehydes and found that the CAB catalyst gives higher syn/anti selectivity than BINOL/Ti catalysts in the reaction [4]. CAB complex 2 was utilized in asymmetric synthesis of chiral polymers using a combination of dialdehyde and bis(allylsilane) [5] or monomers possessing both formyl and allyltrimethylsilyl groups [6]. 

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]. 

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. 

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