Catalytic Enantioselective Preparation of α‐Substituted Allylboronates: One‐Pot Addition to Functionalized Aldehydes and a Route to Chiral Allylic Trifluoroborate Reagents

Abstract

Additions of allylic boron reagents to aldehydes have evolved into one of the most popular methods for stereoselective CÀC bond formation.[1] Compared to dialkyl allylic boranes, allylic boronic esters are often more advantageous as a class of reagents because of their superior stability. Three strategies have been developed for the control of enantiofacial selectivity in additions of allylic boronates to achiral aldehydes: 1) the use of a chiral diol or a diamine auxiliary as the two nonallylic substituents on the boron center; [2] 2) the use of chiral Lewis and Brønsted acid catalysis with achiral boronates; [3] and 3) the use of optically pure a-substituted reagents (so-called a-chiral allylboronates).[4] The preparation of chiral a-substituted allylboronates 1 and their additions to aldehydes were pioneered by Hoffmann and co-workers. [4] Regrettably, these reagents have remained underused in part because of their stepwise preparation based on a Matteson asymmetric homologation of chiral alkenylboronates. [5,6] The reagent-controlled additions of 1 to aldehydes proceed with near-complete transfer of chirality to give two diastereomeric products 4 and 5 (Scheme 1). These Z and E allylic alcohols are epimeric, and their ratio is highly dependent on the nature of the a substituent R 1 and the nature of the boronic ester.[4] The ratio of 4 and 5 can be explained in terms of steric and dipolar effects on the two competing transition structures 2 and 3. With a nonpolar alkyl substituent R 1 , steric interactions play a dominant role. The chairlike transition structure 2 can be destabilized by a steric interaction between a large boronic ester and the pseudoequatorial a substituent R 1 . On the other hand, the transition structure 3 features unfavorable allylic interactions that result from the pseudoaxial position of the R 1 substituent. The common use of a hindered ester, such as pinacolate, aggravates the interactions between R 1 and the methyl groups of the pinacol moiety in 2. Thus, in this case transition structure 3 is more probable and leads to mixtures of products 4 and 5 in modest selectivities. [7] In our view, two major issues need to be resolved to render chiral a-substituted allylboronates attractive reagents: a simple catalytic enantioselective method for their preparation and full diastereocontrol of the ratio 4/5 by a suitable optimization of reagent (R 1 , (OR) 2 ) and reaction conditions. Here, we report an approach that successfully addresses these two issues and provides a simple and efficient method for enantioselective aldehyde allylation.Prompted by the recent report of Alexakis and coworkers [8a] on the copper-catalyzed S N 2' allylic alkylation of cinnamyl chloride using chiral phosphoramidite ligands (L*), [8,9] we envisioned that 3-halopropenylboronates 6 [10] could be suitable substrates in this reaction [Eq. (1)]. With these substrates, however, the noncatalyzed (that is, background) allylic Matteson homologation may pose a serious threat to the enantioselectivity of this process.[1...

Enantioselective Synthesis of (E)‐δ‐Boryl‐Substituted anti‐Homoallylic Alcohols Using Palladium and a Chiral Phosphoric Acid

“…An electronically and sterically diverse array of aromatic aldehydes 1a-e gave the corresponding homoallylic alcohols 3aa-ea in yields ranging from 78 to 90 %(entries 1-5). In addition, 2-furaldehyde (1f), cinnamaldehyde (1g), as well as aliphatic aldehydes such as 2phenylacetaldehyde (1h)a nd cyclohexanecarbaldehyde (1i) successfully participated in the allylation reaction (entries [6][7][8][9]. Of note was that good to high anti/syn ratios, E/Z ratios, and enantioselectivities were observed in all cases.T he anti/ syn ratios (3:4)a sw ell as the E/Z ratios with regard to the double-bond geometry of the anti-configured isomer 3 were higher than 95:5 in most cases.The enantioselectivities of the E-configured anti-isomers of 3 ranged from 91 to 99 % ee.…”

“…[2,3] Fore xample,( E)-g-substituted allylic boronates [1-(boryl)alk-2-enes] are generated in situ from 1-(boryl)alk-1-enes by iridium(I)catalyzed double-bond transposition, and immediately undergo chiral phosphoric acid catalyzed allylation of aldehydes to produce anti-homoallylic alcohols with high enantioselectivity. [2b,4] Recently,a na symmetric allylation using chiral allylic boron reagents [5,6] functionalized with another semi-metal element, like tin, silicon, and boron, [7][8][9] has attracted much attention because the semi-metal elements remaining in the products allow av ariety of additional transformations.F or example,R oush and co-workers generated enantioenriched (S)-(E)-g-substituted a-stannyl allylic boranes from allenylstannane,and synthesized (E)-d-stannylsubstituted anti-homoallylic alcohols with high enantioselectivity ( Figure 1a). [8] This strategy was successfully applied to the asymmetric total syntheses of (À)-tirandamycin C [8d] and (+ +)-crocacin C. [8e] Enantioenriched (S)-(E)-g-substituted asilyl allylic boranes are also feasible starting from allenylsi-lane.…”

Highly Stereoselective Synthesis of Z‐Homoallylic Alcohols by Kinetic Resolution of Racemic Secondary Allyl Boronates

“…In this case, the main challenge for the efficient kinetic resolution to operate would be to enforce a preference for the transition state with either an equatorial (leading to ( E )‐ 6 ) or axial (leading to ( Z )‐ 5 ) position of the R 1 group. Since E isomers can be readily obtained by a number of existing methods,3, 5c, 6a–d we focused our attention on Z isomers, for which there are currently only a few examples, in which chiral auxiliaries or the chiral pool are employed 6e,f. 8…”

Allylation Reactions of Aldehydes with Allylboronates in Aqueous Media: Unique Reactivity and Selectivity that are Only Observed in the Presence of Water

“…This reaction was further applied to catalytic asymmetric alkylallylation, chloroallylation, and alkoxyallylation processes and the synthetic utility of these reactions has been demonstrated. cently, Lewis acid catalyzed allylboration reactions were independently reported by Hall and co-workers [19,20] and by Miyaura and co-workers. [21] These allylation reactions were accelerated by catalytic amounts of external Lewis acids.…”

“…[7] Two years later, Favre, Gaudemar, and co-workers reported the allylation of aldehydes by using allylboronic ester. Based cently, Lewis acid catalyzed allylboration reactions were independently reported by Hall and co-workers [19,20] and by Miyaura and co-workers. [10] The reactions proceeded without catalysts on the basis of a Lewis acidic boron atom through Zimmerman's six-membered transition states to exclusively afford g-addition products.…”