Allylation Lewis base-promoted

The first example of a chiral Lewis base promoted allylation was given by Denmark and coworkers in 1994 [45], Stoichiometric amounts of chiral phospho-ramide R,R)-20 facilitated the enantioselective allylation (Scheme 15). There was a complete stereochemical correlation between the geometry (ElZ) of allylsilane and the diastereomeric ratio (synlanti) of the products. 

Leighton has combined this concept of strained silacycles [62-66] with the asymmetric allylation chemistry in a series of pubhcations [60, 67-70], Leighton s aUyhc silacyclopentane 29 [67] (Scheme 20) works equally for allylation of aromatic and ahphatic aldehydes in the absence of additional Lewis bases (promoter activator) or Lewis acids with high yield and enantioselectivity. The mechanism of... 

Pentacoordinate silicon, in the form of allyltrichlorosilane, in the presence of DMF or HMPA, also undergoes allylation with aldehyde [97,98], The Lewis base-promoted approach has the merit of operational convenience. Stereoselective formation of allylic trichlorosilanes is achieved by copper-catalyzed coupling of allylic chloride and trichlorosilane or by palladium-catalyzed hydrosilylation of 1,3-dienes (Sch. 56) [99],... 

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. 

Wang, Z., Kisanga, P. and Verkade, J.G. (1999) P( PrNCH2CH2)3N an effective Lewis base promoter for the allylation of aromatic aldehydes with allyltrimethylsilane. The Journal of... 

An interesting and stereoselective synthesis of 1,3-diols has been developed which is based on Lewis acid promoted reactions of /f-(2-propenylsilyloxy (aldehydes. Using titanium(IV) chloride intramolecular allyl transfer takes place to give predominantly Ag/r-l,3-diols, whereas anti-1,3-diols, formed via an / / /-molecular process, are obtained using tin(IV) chloride or boron trifluoride diethyl ether complex71. 

If the latter reaction proceeds through a closed transition state (e.g., 5 in Scheme 7.2), good diastereocontrol can be expected in the case of trans- and cis-CrotylSiCl3 (2b/2c) [14, 15]. Here, the anh-diastereoisomer 3b should be obtained from trans-crotyl derivative 2b, whereas the syn-isomer 3c should result from the reaction of the cis-isomer 2c (Scheme 7.2). Furthermore, this mechanism creates an opportunity for transferring the chiral information if the Lewis base employed is chiral. Provided that the Lewis base dissociates from the silicon in the intermediate 6 at a sufficient rate, it can act as a catalyst (rather than as a stoichiometric reagent). Typical Lewis bases that promote the allylation reaction are the common dipolar aprotic solvents, such as dimethylformamide (DMF) [8,12], dimethyl sulfoxide (DMSO) [8, 9], and hexamethylphosphoramide (HMPA) [9, 16], in addition to other substances that possess a strongly Lewis basic oxygen, such as various formamides [17] (in a solution or on a solid support [7, 8, 18]), urea derivatives [19], and catecholates [10] (and their chiral modifications [5c], [20]). It should be noted that, upon coordination to a Lewis base, the silicon atom becomes more Lewis acidic (vide infra), which facilitates its coordination to the carbonyl in the cyclic transition state 5. 

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]. 

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. 

The observed activation of allyltrihalosilanes with fluoride ion and DMF and the proposition that these agents are bound to the silicon in the stereochemistry-determining transition structures clearly suggested the use of chiral Lewis bases for asymmetric catalysis. The use of chiral Lewis bases as promoters for the asymmetric allylation and 2-butenylation of aldehydes was first demonstrated by Denmark in 1994 (Scheme 10-31) [55]. In these reactions, the use of a chiral phos-phoramide promoter 74 provides the homoallylic alcohols in high yield, albeit modest enantioselectivity. For example, the ( )-71 and benzaldehyde affords the anti homoallylic alcohol 75 (98/2 antUsyn) in 66% ee. The sense of relative stereoinduction clearly supports the intermediacy of a hexacoordinate silicon species. The stereochemical outcome at the hydroxy center is also consistent with a cyclic transition structure. 

The first example of chiral Lewis base-catalyzed allylation of carbonyl compounds was shown by Denmark et al. [35]. They surveyed a variety of achiral and chiral Lewis bases as stoichiometric reagents to promote the addition of al-lyltrichlorosilane to benzaldehyde and found that the chiral phosphoramide 14 was a superior chiral promoter. When crotyltrichlorosilane was employed, the diastereoselectivity anti/syn) of the product was dependent on the geometry of the crotylsilane. Based on the stereochemical outcome, the reaction was proposed to proceed via closed transition structures involving hexacoordinate siH-conates. The potential for catalysis was proved using a 25 mol % of 14 at -78 °C and a moderate enantiomeric excess was obtained (Scheme 13). 

Allylation. Silver tosylate is used in combination with urea, a Lewis base catalyst, to promote allylation of aldehydes with allyltrichlorosilane. 

Tan et al. [44] succeeded in developing a new urea-sulfmimide catalyst that promotes the indium mediated allylation of acyUiydrazones (Scheme 9.9). Incorporation of Lewis base functionality in proximity to the urea moiety is designed to promote the addition of organometallic reagents to the C=N bond of acylhydrazones through dual activation. 

Sakurai pioneered the field of nucleophilic activation of reagents 21.5 by employing stoichiometric amounts of CsF or dilithium catecholates for highly diastereoselective allylation of aldehydes with allyltrihalosilanes 21.5. Later, it was demonstrated that the common dipolar aprotic solvents possessing a strongly Lewis basic ojg gen promote the allylation reaction. Thus, Kobayashi revealed that DMF can act both as a solvent and a Lewis-base activator. Denmark further established that, in contrast to DMF that was required in large excess to promote the allylation of aldehydes, HMPA can be used in substoichiometric quantities. 

However, Lewis bases of this type are less practical than the previously described phoshoramides (Figure 21.1) and ALoxides (Figures 21.2 and 21.3) as they are commonly required in more than stoichiometric amounts. Furthermore, these chiral promoters are rarely recovered due to reduction of the sulfoxide functionality or decomposition during the reaction. A positive nonlinear effect observed in the asymmetric allylation of aldehydes using chiral sulfoxide 21.30 as a promoter suggests a transition state with two molecules of the catalyst coordinated to silicon in the carbon-carbon bond-forming event. - ... 

Studied using Lewis acid, " Lewis base, enzymatic, bifunctional, and Br0nsted-acid-catalyzed processes. For example, Berkessel and co-workers have employed bifunctional thioureas 90 and 175 in the presence of allyl alcohol to promote the DKR of racemic azlactones and oxaz-inanones, " while Connon and co-workers have shown that the bifunctional cinchona alkaloid urea derivative 177... 

To be accurate, the definition should be restricted to asymmetric reactions catalyzed by a combination of l,r-binaphthalene-2,2 -diol (BINOL, 4) and Ti(0 -Pr)4. Nonetheless, this chapter will give some background on non-chiral Lewis acid promoters, and include other asymmetric catalytic systems. We will not discuss the allylations that are promoted by Lewis bases, which are reviewed elsewhere, nor cover the reactions with other electrophiles. Excellent reviews already exist on "Selective Reactions Using Allylic MetaM and Catalytic Enantioselective Addition of Allylic Organometallic Reagents to Aldehydes and Ketones , as well as in the comprehensive monograph "Modern Carbonyl Chemistry. The use of BINOL-based catalysts in other fields of organic synthesis has also been reviewed. ... 

As a Carbon Nucleophile in Lewis Base-catalyzed Reactions. Allylation of alkyl iodides with allyltrimethylsilane proceeds in the presence of phosphazenium fluoride. Tetra-butylammonium triphenyldifluorosilicate (TBAT) is useful for allylation of aldehydes, ketones, imines, and alkyl halides with allyltrimethylsilane (eq 63). 55 Similarly, TBAHF2 is an effective catalyst for allylation of aldehydes. The homoallylamines are synthesized from allyltrimethylsilane and imines with a catalytic amount of TBAF (eq 64). The reactions of thioketones as well as sulfines with allyltrimethylsilane can be mediated by TBAF to give allylic sulfides and allyl sulfoxides, respectively. Besides fluoride ion, 2,8,9-triisopropyl-2,5,8,9-tetra-aza-1-phosphabi-cyclo[3.3.3]undecane promotes the allylation of aldehydes with allyltrimethylsilane as a Lewis base catalyst (eq 65). ... 

The first report on the conceptually new asymmetric catalysis described that both a stoichiometric amount of SiCU and a catalytic amount of chiral phosphoramide (107) promote highly enantioselective allylation and propargylation of aromatic aldehydes with allyl- and allenyl-tributylstannane, respectively [41], The allylation does not proceed without (107). In the proposed mechanism, SiCU, a weak achiral Lewis acid, accepts the Lewis base (107) to form a strong chiral Lewis acid by polarization of the Si-Cl bonds. The active Lewis acid promotes the asymmetric reaction to give trichlorosilylated adducts with regeneration of (107) (Scheme 9.74). 

Denmark has also made significant contributions to the evolution of this chemistry by introducing the concept of Lewis base activation of Lewis acids. Its validity and synthetic potential were demonstrated first by achieving the highly enantiose-lective allylation and propargylation of aldehydes with 2 as an optimal catalyst as exemplified in Scheme 7.4 [5]. The key to this asymmetric catalysis is the generation of a chirally modified and activated silicon Lewis acid by the 2-promoted ionization of the weakly Lewis acidic SiCLj. 

TS, which is usually based on the chair (Zimmerman-Traxler) model. This pattern is particularly prevalent for the allylic borane reagents, where the Lewis acidity of boron promotes a tight cyclic TS, but at the same time limits the possibility of additional chelation. The dominant factors in these cases are the E- or Z-configuration of the allylic reagent and the conformational preferences of the reacting aldehyde (e.g., a Felkin-type preference.)... 

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