Pinacol diastereoselectivity

It is interesting to speculate that asymmetric induction may be the consequence of the exo anomeric effect, a stereoelectronic effect that favors the conformation 5 that places the aglycone O-C bond antiperiplanar to the pyran C(1) —C(2) bond7fi. Related asymmetric induction has also been observed in aldehyde addition reactions of the related, but racemic, pinacol (Z)-y-(tetrahydropyranyloxy)allylboronate49. As indicated in the examples above, however, the level of diastereoselectivity is modest and the only application in asymmetric synthesis is Wuts exo-brevicomin synthesis75. 

A variety of such ternary catalytic systems has been developed for diastereoselective carbon-carbon bond formations (Table). A Cp-substituted vanadium catalyst is superior to the unsubstituted one,3 whereas a reduced species generated from VOCl3 and a co-reductant is an excellent catalyst for the reductive coupling of aromatic aldehydes.4 A trinuclear complex derived from Cp2TiCl2 and MgBr2 is similarly effective for /-selective pinacol coupling.5 The observed /-selectivity may be explained by minimization of steric effects through anti-orientation of the bulky substituents in the intermediate. 

Based on these observations [18,19,23], a variety of modified catalytic systems have been reported for the diastereoselective reductive carbon-carbon bond formation (Scheme 8). A complex 5 derived from Cp2TiCl2 and MgBr2 is proposed to be an efficient catalyst for the DL-diastereoselective pinacol coupling of aromatic aldehydes [24], Addition of a solution of benzalde-... 

The above-mentioned results indicate the additive effect of protons. Actually, a catalytic process is formed by protonation of the metal-oxygen bond instead of silylation. 2,6-Lutidine hydrochloride or 2,4,6-collidine hydrochloride serves as a proton source in the Cp2TiCl2-catalyzed pinacol coupling of aromatic aldehydes in the presence of Mn as the stoichiometric reduc-tant [30]. Considering the pKa values, pyridinium hydrochlorides are likely to be an appropriate proton source. Protonation of the titanium-bound oxygen atom permits regeneration of the active catalyst. High diastereoselectivity is attained by this fast protonation. Furthermore, pyridine derivatives can be recovered simply by acid-base extraction or distillation. 

The 1,5- and 1,6-dialdehydes 22 and 24 undergo the annulative pinacol coupling to give the cyclic vzc-diols 23 and 25, respectively (Scheme 13) [29]. The vanadium-catalyzed intramolecular coupling reaction of 1,5-diketone 26 also proceeds with excellent selectivity (Scheme 14) although the intermolecular coupling of ketones such as acetophenone results in low diastereoselectivity under these conditions [21]. 

Intramolecular pinacol reduction. Sml2 can promote intramolecular reductive conpling of keto aldehydes to provide 2,3-dihydroxycyclopentanecarboxylates with marked diastereoselectivity.2... 

Intermolecular coupling Many papers on hydrodimerization of aromatic carbonyl compounds have appeared indicating the importance of this reaction. The rac/meso ratio for the pinacolization of acetophenone in aqueous ethanol ranges between 0.9 and 1.4 in acidic medium and between 2.5 and 3.2 in basic medium. The diastereoselectivity is independent of the cathode material mercury, tin, or copper. Electrolysis conditions such as current density, potential, or current-controlled electrolysis also do not influence the diastereoselectivity. The same holds for propiophenone. For benzaldehyde, the rac/meso ratio is 1.1 to 1.2 in acidic as well as in basic media [283]. In the presence... 

Aldehyde 13, readily prepared by a four step synthesis from L-threonine,3a-i5 was treated with the known (Z)-7-methoxyallylboronate 1412a,c. This reaction, as with other reactions of pinacol allylboronates, was relatively slow and required 24-48 h at room temperature to reach completion. It was, however, extremely selective ana provided homoallyl alcohol 15 in 70% yield with greater than 95% diastereoselectivity. The stereochemistiy of this compound was quickly verified by conversion to 3 as shown in Figure 7.3a We now believe that this reaction proceeds by way of the Conforth-like transition state depicted in Figure 7, and not by way of a Felkin transition state as suggested in our original ublication, since a serious nonbonded interaction exists between the (Z)-methoxyl group and the C(3) substituents of 13 in the Felkin transition state. A... 

The use of chiral Br0nsted acids is illustrated in Eq. 93 as a method for catalyst-controlled double diastereoselective additions of pinacol allylic boronates. Aside from circumventing the need for a chiral boronate, these additions can lead to very good amplification of facial stereoselectivity. For example, compared to both non-catalyzed (room temperature, Eq. 90) and SnCU-catalyzed variants, the use of the matched diol-SnCU enantiomer at a low temperature leads to a significant improvement in the proportion of the desired anti-syn diastereomer in the crotylation of aldehyde 117 with pinacolate reagent (Z)-7 (Eq. 93). Moreover, unlike reagent (Z)-ll (Eq. 91) none of the other diastereomers arising from Z- to E-isomerization is observed. 

Diastereoselectivity of a catalytic pinacol coupling using TiCU, zinc, and acetic anhydride at room temperature for 24 h in DME is low (dljmeso = 60/40). The ratio improves a little by changing the reductant to aluminum. ... 

Treatment of alkanedials with the reagent for pinacol coupling causes intramolecular cyclization leading to 1,2-cycloalkanes. The diastereoselectivity depends on the ring size formed (Equation (16)). ... 

I, 5-dithioniabicyclo[3.3.0]octane bis(trifluoromethanesulfonate) 7 in acetonitrile at 50°C. The salt promotes pinacol coupling of aromatic ketones even at —40 °C. In addition, the diastereoselectivity dl meso) of the coupling reaction of acetophenone in acetonitrile at —40°G is 94 6. "... 

Although yields and diastereoselectivities are moderate, a cross-pinacol coupling reaction between a 1,2-diketone and an aldehyde is accomplished with Sml2 in the presence of HMPA. ... 

Low-valent niobium and tantalum are also effective for homocoupling of aldehydes leading to 1,2-diols. " Not only commercially available NbClglDME) but also a combination of NbCls and zinc can be used for the pinacol coupling. Reactions in a mixed solvent of 1,4-dioxane and toluene (1 4) give better diastereoselectivity than those in DME or THE (Equation (52)). ... 

Stilbene diols such as 3 are gaining prominence both as synthetic intermediates and as effective chiral auxiliaries. While the diols can be prepared in high by Sharpless dihydroxylation, it would be even more practical to prepare them by direct asymmetric pinacol coupling. N. N. Joshi of the National Chemical Laboratory in Pune reports (J. Org. Chem. 68 5668,2003) that 10 mol % of the inexpensive Ti salen complex 2 is sufficient to effect highly enantioselective and diastereoselective pinacol coupling of a variety of aromatic aldehydes. Most of the product diols are brought to >99% by a single recrystallization. 

The pinacol-type coupling of aliphatic aldehydes, in the presence of niobium(IH) salts, occurs, with a high anti diastereoselectivity (equation 131)512. In the case of aromatic aldehydes and ketones the alkene product is sometimes formed513. In both cases the cyclic acetals may also be formed. 

The samarium-lV-bromosuccinimide combination reductively dimerizes carbonyl compounds.163 This pinacol-type coupling gives diols in 60-80% yield, with some diastereoselectivity the by-product from simple reduction (i.e. alcohol) is typically 5-10%. The conditions suggest a single electron transfer to give carbonyl radical anion, which then self-couples. Even congested ketones such as benzophenone and fluorenone worked well. 

To determine the diastereoselectivity of the above bora-ene reaction, boronate 193 derived from a-pinene was synthesized. Reaction of a-pinene 192 with Schlosser s base (BunLi + KOBu ) furnishes the allyl carbanion, which upon treatment with triisopropyl borate and subsequent transesterification with pinacol yields a-pinanyl pinacol boronate 193. Bora-ene reaction with this allyl boronate and S02 at — 78 °C in CH2CI2 yields the mixed anhydride 194 as a 2.3 1 mixture of diastereomers upon removal of excess S02. Treatment of this mixture of anhydrides with aryl Grignard led to the formation of two diastereomers of aryl sulfoxides 195 in 3.2 1 ratio (Scheme 33) <2006TL2783>. 

Cross pinacol coupling of aldehydes. Pedersen et al.2 have reported the first general method for stereoselective pinacol coupling of aldehydes by use of this vanadium(II) reagent. Aryl aldehydes couple in the presence of 1 to pinacols in >90% yield and with high diastereoselectivity (dllmeso = 12-100 1). Aliphatic aldehydes under similar conditions couple only slowly, but depending on the struc-... 

Lewis acids and Bu4NI catalyzed allylboration with potassium allyl- and crotyltrifluoroborates (Equation (154)).30,40 620,621 The reaction of pinacol ester derivatives was very slow even at room temperature, but Sc(OTf)3 smoothly catalyzed the addition at — 78 °C with high diastereoselectivity (Equation (155)622 and (156)623,624). A palladium pincer complex catalyzed the addition of trifluoroborate to tosylimines (Equation (157)).625... 

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