Enantioselectivity achiral aldehydes

The enantioselectivities of the reactions of representative achiral aldehydes and chiral allylboron reagents arc compared in Table 4. A comparison of the enantioselectivities of the (Z )-2-butenyl reagents appears in Table 5, while Table 6 provides a similar summary of the reactions of the (Z)-2-butenyl and 3-methoxy-2-propcnyl reagents. A 3-diphenylamino-2-propenyl reagent was recently reported102. 

Results of the asymmetric 2-propenylborations of several chiral a- and /i-alkoxy aldehydes are presented in Table 11 74a-82 84. These data show that diisopinocampheyl(2-propenyl)borane A and l,3-bis(4-methylphenylsulfonyl)-4,5-diphenyl-2-propenyl-l,3,2-diazaborolidine C exhibit excellent diastereoselectivity in reactions with chiral aldehydes. These results are in complete agreement with the enantioselectivity of these reagents in reactions with achiral aldehydes (Section 1.3.3.3.3.1.4.). In contrast, however, the enantioselectivity of reactions of the tartrate 2-propenylboronate B (and to a lesser extent the tartrate (/i)-2-butenylhoronate)53b is highly... 

Dimethylphenylsilyl-2-propenylboronate 7 is more enantioselective (81-87% ee with achiral aldehydes) than the 2-[cyclohexyloxy(dimethyl)silyl] compound 8 (64-72% ee), and consequently the former generally gives better results especially in mismatched double asymmetric reactions. Nevertheless, the examples show that appreciable double diastereoselection may be achieved with both reagents in many cases. 

Chiral, nonracemic allylboron reagents 1-7 with stereocenters at Cl of the allyl or 2-butenyl unit have been described. Although these optically active a-substituted allylboron reagents are generally less convenient to synthesize than those with conventional auxiliaries (Section 1.3.3.3.3.1.4.), this disadvantage is compensated for by the fact that their reactions with aldehydes often occur with almost 100% asymmetric induction. Thus, the enantiomeric purity as well as the ease of preparation of these chiral a-substituted allylboron reagents are important variables that determine their utility in enantioselective allylboration reactions with achiral aldehydes, and in double asymmetric reactions with chiral aldehydes (Section 1.3.3.3.3.2.4.). 

Ley developed an efficient tandem organocatalytic synthesis of chiral dialkyl 3-alkyl-l,2,3,6-tetrahydropyridazine-1,2-dicarboxylates 272 from /3-oxohydrazines 271. Compound 271 was obtained from commercially available achiral aldehydes and dialkyl azodicarboxylates using (6)-pyrrolidinyl tetrazole as the chiral catalyst. This synthesis proceeds with good to excellent yields (58-89%) and enantioselectivities (69-99% ee). The highest ee values are obtained for the most bulky di-/-butyl azodicarboxylate and the shortest branched aldehydes (Scheme 67) <2006SL2548>. 

The formation of 1-deuterio primary alcohols, such as (S)-8 from achiral aldehydes with catecholborane-d in the presence of an enantioselective catalyst (for configurational assignment, see p 453)76. 

The enantioselective aldol and Michael additions of achiral enolates with achiral nitroolefins and achiral aldehydes, in the presence of chiral lithium amides and amines, was recently reviewed354. The amides and amines are auxiliary molecules which are released on work-up (equation 90 shows an example of such a reaction). 

Corey, E. J. Choi, S. Highly enantioselective routes to Darzens and acetate aldol products from achiral aldehydes and t-butyl bromoace-tate. Tetrahedron Lett. 1991, 32, 2857—2860. 

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]. 

Roush et al. discovered that the tartrate ester-modified allylboronates, such as diisopropyl tartrate allylboronate (.S, .S )-41, react with achiral aldehydes to give the homoallylic alcohols 42 in good yields and high levels of enantioselectivity of up to 87% ee when the reaction is carried out in toluene in the presence of 4-A molecular sieves20 (Scheme 3.1q). To rationalize the asymmetric induction realized by 41, two six-membered transition states were compared (Scheme 3.1r). It was reasoned that transition state A was favored over transition state B due mainly to the nonbonded electronic repulsive interactions of the lone-pair electrons of the aldehyde oxygen and the carbonyl oxygen of the tartrate ester. 

A catalytic asymmetric aldol-type reaction of ketene silyl acetals with achiral aldehydes also proceeds with the CAB catalyst (2), which can furnish syn-p-hydroxy esters with high enantioselectivity (eq 6). 

Condensation of achiral aldehydes with allylsilanes promoted by CAB catalyst (2) (20 mol %) at —78 °C in propionitrile produces homoallylic alcohols with excellent enantioselectivity (eq 7). 

Allystannanes are more nucleophilic than allylsilanes. Addition of achiral allylstannanes to achiral aldehydes in the presence of (1) (20 mol %) and Trifluoroacetic Anhydride (40 mol %) also affords homoallylic alcohols with high diastereo- and enantioselectivities (eq 8). 

Reactions with Achiral Aldehydes. The reaction of tartrate allylboronates with achiral aldehydes proceeds with moderate to excellent enantioselectivity (60-92% ee) and high yield (80-90%). Simple aliphatic aldehydes give good enantioselectiv-ities (decanal 86% ee, CyCHO 87% ee, eq 2), while p-alkoxy and conjugated aldehydes give diminished selectivities (60-80% ee) (eq 3). The enantioselectivity is highly temperature and solvent dependent. Best results for reactions with the vast majority of aldehydes are obtained in toluene at —78 °C. 4°A molecular sieves are included to ensure that the reaction is anhydrous. Other tartrate esters (e.g. diethyl tartrate) may also be used without loss of enantioselectivity. 

Asymmetric Crotylboration . Reagents for crotylboration are prepared from 2,5-dimethyl-S-methoxyborolane (eq 5) by addition of (Z)- or ( )-crotylpotassium under standard conditions. Reactions with representative achiral aldehydes are 93-96% diastereoselective and 86-97% enantioselective for the major diastereomer (eqs eq 12 and eq 13). Results with chiral aldehydes conform to the rule of double asymmetric synthesis. ... 

The asymmetric aldol reaction of enol silyl ethers of thioesters with aldehydes is performed in high enantiomeric excess by employing a chiral promoter, tin(II) trifluoromethanesulfonate coordinated with chiral diamine 1 and tri-n-butyltin fluoride (eqs 20 and 21). Highly enantioselective aldol reactions of achiral ketene silyl acetals with achiral aldehydes are carried out by means of the same chiral promoter (eq 22). ... 

Very recently, a limited survey of the CAB and Keck BINOL methodology with crotyltributyltin was conducted by Marshall and Palovich (Table 3) [50b]. A modified CAB, prepared from the 2,6-dimethoxybenzoic ester of (l ,jR)-tartaric acid, and 1.5 equiv. BH3-THF was used in the addition of crotyltributyltin and allyltributyltin to representative achiral aldehydes in the presence of 2 equiv. (Cp3C0)20. Addition to crotyltin proceeded with good to excellent diastereoselectivity and enantioselectivity to give syn adducts in 70-93 % ee as major products (78 22-92 8). The addition of allylstannane to cyclohexanecarboxaldehyde afforded the (R) adduct in 55 % ee. In contrast, the use of Keck s BINOL catalyst gave an allyl adduct in 87 % ee. Addition of crotylstannane to cyclohexanecarboxaldehyde with this catalyst led, however, to a 65 35 mixture of syn and anti adducts 43 (R = Me) and 44 (R = Me) in 95 % and 49 % ee. 

In Section 3.5.2 we described the highly enantioselective addition of dialkylzinc to achiral aldehydes catalyzed by chiral 1,2-disubstituted ferrocenyl amino alcohols, which shows high stereoselectivity even in the alkylation of a-branched aliphatic aldehydes. In order to further develop the characteristics of our catalysts, the ethylation of aldehydes substituted with an a-thio- and seleno group was investigated. 

In recent years the synthetic potential and mechanistic aspects of asymmetric catalysis with chiral Lewis base have been investigated. Aldol addition reactions between trichlorosilyl enolates with aldehydes have been also intensively studied. Now, full investigations of the trichlorosilyl enolates derived from achiral and chiral methyl ketones, in both uncatalysed and catalysed reactions with chiral and achiral aldehyde acceptors have been reported. The aldol addition is dramatically accelerated by the addition of chiral phosphoramides, particularly (137) and proceed with good to high enantioselectivity with achiral enolates and aldehydes (Scheme 34). ... 

Table 12 Enantioselective Allylation of Achiral Aldehydes Catalyzed by TiCl4...

Taddei and coworkers reported that chiral allyltrimethylsilanes containing an optically active ligand derived fiom (-)-myrtenal attached to silicon (96) underwent enantioselective addition reactions with achiral aldehydes (Scheme 46) to give, after acid hydrolysis, optically active homoallyl alcohols (98). A variety of Lewis acids were examined to optimize enantiomeric excess, and TiCU was found to be the most effective catalyst. The results of the TiCU-promoted additions are reported in Table 12. ... 

Roush, W. R., Ando, K., Powers, D. B., Halterman, R. L., Palkowitz, A. D. Enantioselective synthesis using diisopropyl tartrate-modified (E)-and (Z)-crotylboronates reactions with achiral aldehydes. Tetrahedron Lett. 1988, 29, 5579-5582. 

The asymmetric allylation of achiral aldehydes with allyltrichlorosilane has also been promoted by birsoquinoline A,W-dioxide and derivatives (Scheme 10-32) [58]. The reaction gave the highest yield and enantioselectivities when aromatic aldehydes were employed. For example, the biisoquinoline A. A -dioxide (80) pro-... 

Keck [89a-c], Tagliavini [89d,e], and Yu [89f] have extensively studied the BINOL-Ti- or binol-Zr promoted reactions of achiral aldehydes with allylstan-nanes. The initial studies employed BINOL and either Ti(Oi-Pr)4 or TiCl2(0/-Pr)2 as the Lewis acid promoter in the reaction of achiral aldehydes with allyltributyl-stannane. The reaction affords good yields of the desired homoallylic alcohol with a high degree of enantioselectivity even with as little as 10 mol% of the chiral catalyst (Scheme 10-49) [89a]. The rate and turnover of the catalytic, asymmetric allylation reaction have also been optimized. It was found that when /-PrSSiMe3 is added to the reaction, a rate acceleration occurs, allowing as little as 1-2% of the catalyst to be used [89 fj. 

The reaction of methallyltri-n-butylstannane 117 with achiral aldehydes is also effectively promoted by the binol-Ti complex [89 c]. In all but one case (cyclo-hexanecarboxaldehyde), the yields and enantioselectivities observed with the methallylstannane are identical or higher than those obtained in the reactions with allyltributylstannane with only 10 mol% of the binol-Ti complex (Scheme 10-50). Insight into the nature of the titanium catalyst is provided by the observation of asymmetric amplification [89 b] and chiral poisoning [89 g]. An intruiging hypothesis on the origin of enantioselection in allylation and related reactions [89 h]. 

The catalytic asymmetric propargylation [108] and allenylation [109] of achiral aldehydes has been performed with high levels of enantioselection. The asymmetric propargylation promoted by the chiral Lewis acid derived from bind and Ti(0/-FT)4 are representative. Between 50 and 100 mol% of titanium is required for these reactions to go to completion (Scheme 10-70). The reaction of benzalde-hyde with allenyltributylstannane 170 and the chiral promoter produced the homo-propargylic alcohol 171 in >99% ee and 48% yield (7% of the undesired allenyl alcohol was also obtained). 

The asymmetric allylboration of achiral aldehydes with a substituted chiral al-lylborolane 193 and ( )- or (Z)-194 has been reported [128]. The enantioselectiv-ity observed with (5)-193 at -100 C and aldehydes is uniformly high with all of the achiral aldehydes examined (Scheme 10-75). The enantioselection observed with the borolane 193 is proposed to be primarily steric in origin and not from any stereoelectronic component. The reaction likely proceeds via a closed, six-membered transition structure in which the aldehyde is coordinated such that the trimethylsilyl group is oriented anti to the developing B-0 bond. 

The reactions of selected achiral aldehydes with the allyl- and 2-butenylboro-nates 195, ( )- and (Z)-196, and 197 illustrate the power of reagent control in synthesis (Table 10-16). The highest enantioselectivities were observed with the... 

The chiral allyl- and 2-butenylboronates derived from tartrate esters (Chart 10-5) have been used in combination with a wide variety of chiral aldehydes to produce homoallylic alcohols in high yield and moderate to high enantioselectivity [124], The results obtained from reaction of selected chiral aldehydes (Chart 10-6) with the tartrate-modified allylboronates 195 and 197 (Chart 10-5) are shown in Table 10-20. As with the achiral aldehydes, the highest enantioselectivities are obtained when the chiral aldehydes are combined with allylboronate 197. A strong reagent-induced selectivity is apparent, but is nevertheless dependent on the intrinsic bias of the aldehyde. 

The InCl3-promoted reaction of enantiomerically enriched a-alkoxystannanes 305 with achiral aldehydes produces a mixture of homoallylic alcohols with a high degree of relative diastereoselectivity and excellent enantioselectivity (Scheme 10-106). A plausible explanation first invokes the formation of indium reagent 306 produced via anti Se2 attack of lnCl3 on the a-alkoxystannane. Addition to the aldehyde can then occur via the chair-like transition structure xxxvii to afford the anti homoallylic alcohol preferentially. 

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