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Michael J Krische - One of the best experts on this subject based on the ideXlab platform.

James P. Morken - One of the best experts on this subject based on the ideXlab platform.

  • catalytic enantioselective 1 2 diboration of 1 3 dienes versatile reagents for stereoselective Allylation
    Angewandte Chemie, 2012
    Co-Authors: Laura T Kliman, Scott N Mlynarski, Grace E Ferris, James P. Morken
    Abstract:

    Polyketides are an important class of natural products that often possess potent biological activity and intriguing chemical structures. Among the methods for constructing these ensembles, the stereoselective addition of allylmetal reagents[1] - particularly allyl boron reagents[2] - to prochiral Carbonyls holds particular prominence. With Type I Allylation reagents[3], this reaction not only delivers functionality that is strategically positioned for establishing appropriate oxygenation patterns, but its stereochemical predictability allows ready access to acetate, propionate, and isobutyrate synthetic equivalents. A limitation of many Allylation reactions, however, is that they deliver products bearing a terminal alkene; if one desires additional substitution or functionality on the olefin, additional synthetic manipulations are often required.[4] In this regard, the vinylogous aldol reaction has proven particularly important as it delivers enoate-derived homoallylic alcohols. Unfortunately, even with the tremendous emphasis placed on the development of catalytic enantioselective vinylogous aldol reactions, an efficienct syn-selective asymmetric propionate version is still unavailable, as is a version that delivers quaternary centers.[5] In this report, we document the first examples of the enantioselective catalytic 1,2-diboration of 1,3-dienes (eq. 1, Scheme 1). As depicted in Scheme 1, the 1,2-diboration of 1,3-dienes delivers allylboron reagents (1) that are perfectly configured to participate in highly selective Allylation reactions.[6,7,8] Importantly, with appropriate oxidative work-up, these reactions deliver vinylogous aldol equivalents that directly address the above-described synthesis limitations. Also of significant consequence, is that the allyl boron in the Allylation product 2 may be subject to other useful bond forming reactions[9] that allow for chain-extending polyketide synthesis. Scheme 1 Strategy for chain-extending polyketide synthesis using 1,2-diboration of 1,3-dienes. To develop the catalytic synthesis strategy in Scheme 1, efforts were first extended toward the development of an enantioselective 1,2-diboration of terminal dienes.[10] A recent study in our laboratory found that enantioselective 1,4-diboration of trans-1,3-dienes could be accomplished with Pt(dba)3 and a chiral phosphonite ligand.[11,12] While evaluation of alternate phosphorous donors revealed ligands that furnished the desired 1,2 diboration, selectivity was suboptimal. A more reliable strategy for obtaining the 1,2-diboration product was to replace the trans diene substrate with cis 1,3-dienes. This approach furnished 1,2-diboration products (3:1 to >20:1 1,2:1,4 selectivity) across a range of substrates and generally occured with excellent enantioselection. After optimization, the ligand structures and reaction conditions depicted in Table 1 were found to be optimal. With respect to polypropionate synthesis, the diboration of cis-pentadiene is paramount and this was found to occur in excellent enantioselectivity (95:5 er) and good yield with ligand L2 (1, Table 1).[13] Aside from the phenyl substituted diene, all other cis dienes examined reacted with outstanding enantiocontrol when employing ligand L1. The diboration of 1,1-disubstituted dienes employing ligand L3 occured with uniformly high levels of stereocontrol (compounds 9–14). Notably, allylic silyl ethers do not engage in allylic borylation under the reaction conditions and tethered alkenes do not appear to perturb the reaction in a detrimental way. Table 1 Catalytic Enantioselective 1,2-Diboration of 1,3-Dienes[a] Significant features of the 1,2-bis(boronate) resulting from the diboration of cis-1,3-dienes are an embedded α-chiral allylboronate and a cis alkene. According to the seminal studies of Hoffmann, it was anticipated that these features would render Allylation reactions highly selective.[14] In an initial experiment, commercially available cis-piperylene was subjected to catalytic diboration with Pt(dba)3 and ligand L2 in THF. The solvent was then removed in vacuo, CH2Cl2 added, and benzaldehyde introduced to the reaction mixture. Upon oxidative work-up, the Allylation product was obtained in moderate isolated yield (48%), however, the stereoisomeric purity was excellent (>20:1 syn:anti, 94:6 er). Examination of the unpurified reaction mixture revealed significant amounts of bis(Allylation) product presumably arising from addition of the initial adduct (15, Table 2) to a second equivalent of aldehyde. To minimize the amount of bis(Allylation), the diboration was executed on a scale that delivered a two-fold excess of 1,2-bis(boronate) relative to aldehyde. This strategy provided good yields of the monoAllylation product for a range of aldehyde substrates (Table 2). As might be expected, the Allylation products were found to possess syn relative stereochemistry (>20:1 in all cases) and the product alkene was found to be in the trans configuration. With respect to synthetic utility, it is significant that aromatic, aliphatic, and α,β-unsaturated aldehydes all participate and the level of chirality transfer from the allylboronate is excellent. Other notable features are that α-branched aldehydes react (entry 6) as do those that bear α-oxygenation (entries 7–9). Importantly, the regioisomeric 1,4-diboration product is not only less reactive in Allylation reactions, but any derived Allylation product is easily removed by silica gel chromatography. A stereochemical model that correlates reactant configuration with product configuration is depicted in ts-1 (graphic, Table 2). Most likely to avoid an A(1,3) interaction with the cis substituent, the CH2B(pin) occupies an equatorial position in the chair-like transition structure. Bond reorganization then delivers the observed enantiomer of product with syn stereoselection and with a trans alkene. Table 2 Asymmetric Allylboration of Carbonyls[a] As exemplified by the production of compounds 9–14 (Table 1), 1,2-diboration of 1,1-disubstituted dienes occurs with excellent selectivity. Similar to the case of cis dienes, it was anticipated that the intermediate bis(boronate) esters would participate in highly selective Carbonyl Allylation reactions. However, with 1,1-disubstitued dienes, the overall reaction sequence would furnish products bearing all-carbon quaternary centers.[15,16] Notably, the added steric encumbrance of these Allylation products appeared to diminish the rate of secondary Allylation such that high yields were obtained even when equimolar amounts of diene, B2(pin)2, and aldehyde were employed (Table 3). Also worth mention is that both the diboration and the Allylation reactions proceeded cleanly in toluene solvent and this allowed the entire sequence to be accomplished in a single flask without solvent swapping operations. Of particular note, either diastereomer of product could be obtained in excellent yield and enantioselectivity simply by employing the appropriate diastereomer of diene substrates. For example, whereas diboration/Allylation employing neral-derived diene 38 furnished product 26 in excellent selectivity, diboration/Allylation employing geranial-derived diene 37 delivered diastereomer 27 with excellent levels of stereocontrol. Similar observations were made with propionaldehyde-derived products 28 and 29. Table 3 Asymmetric Allylboration of Carbonyls with γ,γ-Disubstituted Allylboronates.[a] An attractive feature of the synthesis strategy described above is that the Allylation product can be subjected to bond-forming reactions other than oxidation. As depicted in Scheme 2 (eq. 1), when diene 37 was subjected to diboration and then employed in Allylation, oxidative work-up furnished allylic alcohol 27. Alternatively, subsequent to the Allylation reaction, the intermediate allylboronate was subjected to homologation according to the Matteson protocol (eq. 2).[17] This delivered homoallylic alcohol 39, also in excellent yield and stereoselection. Lastly, it was found that the allylboronation product, when subjected to protodeboronation conditions similar to those described by Aggarwal[9d], was converted to the simple alkene product 40 (eq. 3). In this case, the protonation event occurred predominantly by an SE2′ pathway and delivered bishomoallylic alcohol 40 as the major product. Considering the range of transformations that are available to organoboronates, and the fact that the diboration/Allylation sequence occurs cleanly in aprotic solvent, Allylation intermediates may be directly transformed to a number of other useful building blocks. Scheme 2 Diboration-Allylation-Functionalization Sequence. In conclusion, we have described the catalytic enantioselective 1,2-diboration of 1,3-dienes and have found that the 1,2-bis(boronate) products can be employed in versatile stereoselective Allylation reactions and deliver a range of functionalized chiral building blocks. Further studies on the use of these reactions in complex molecule synthesis are in progress and will be reported in due course.

  • catalytic enantioselective 1 2 diboration of 1 3 dienes versatile reagents for stereoselective Allylation
    Angewandte Chemie, 2012
    Co-Authors: Laura T Kliman, Scott N Mlynarski, Grace E Ferris, James P. Morken
    Abstract:

    More with boron: The development of catalytic enantioselective 1,2-diboration of 1,3-dienes enables a new strategy for enantioselective Carbonyl Allylation reactions (see scheme). These reactions occur with outstanding levels of stereoselection and can be applied to both monosubstituted and 1,1-disubstituted dienes. The Carbonyl Allylation reactions provide enantiomerically enriched functionalized homoallylic alcohol products.

  • asymmetric 1 4 dihydroxylation of 1 3 dienes by catalytic enantioselective diboration
    Journal of the American Chemical Society, 2009
    Co-Authors: Heather E Burks, Laura T Kliman, James P. Morken
    Abstract:

    Asymmetric 1,4-dihydroxylations of 1,3-dienes, and other transformations, are initiated by the Pt-catalyzed enantioselective addition of bis(pinacolato)diboron (B2(pin)2) to conjugated dienes. The studies reported in this communication suggest that both cyclic and acyclic substrates will participate in this reaction; however, dienes which are unable to adopt the S-cis conformation are unreactive. For most substrates, 1,4-addition is the predominant pathway. In addition to oxidation to the derived 2-buten-1,4-diol, stereoselective Carbonyl Allylation with the intermediate bis(boronate) ester is also described.

  • platinum catalyzed tandem diboration asymmetric allylboration access to nonracemic functionalized 1 3 diols
    Organic Letters, 2003
    Co-Authors: Jeremy B Morgan, James P. Morken
    Abstract:

    A single-pot tandem catalytic diene diboration/Carbonyl Allylation reaction is described that uses a commercially available chiral diboron reagent. The chirality of the intermediate diboration adduct is transferred to the product in the Carbonyl Allylation reaction, thereby providing access to enantioenriched chiral products. Notably, the reaction allows for construction of a quaternary stereocenter and furnishes a synthetically versatile C−B bond in the reaction product.

Liuzhu Gong - One of the best experts on this subject based on the ideXlab platform.

Seung Wook Kim - One of the best experts on this subject based on the ideXlab platform.

Yu Lu - One of the best experts on this subject based on the ideXlab platform.

  • Elongation of 1,3-Polyols via Iterative Catalyst-Directed Carbonyl Allylation from the Alcohol Oxidation Level
    Organic Letters, 2009
    Co-Authors: Abbas Hassan, Yu Lu
    Abstract:

    Iterative enantioselective Carbonyl Allylation from the alcohol oxidation level under the conditions of iridium catalyzed transfer hydrogenation enables chain elongation of 1,3-polyols. High levels of catalyst-directed enantioselectivity and diastereoselectivity are observed.

  • 1 n glycols as dialdehyde equivalents in iridium catalyzed enantioselective Carbonyl Allylation and iterative two directional assembly of 1 3 polyols
    Angewandte Chemie, 2009
    Co-Authors: Yu Lu, Abbas Hassan, David J Del Valle, Michael J Krische
    Abstract:

    Nature’s vast collection of polyketide natural products comprises thousands of compounds incorporating polyacetate derived 1,3-diol or higher 1,3-polyol substructures. While numerous protocols for the synthesis of these ubiquitous structural motifs have been advanced,[1] the iterative allylmetallation of aldehydes has found exceptionally broad use.[1–6] For example, asymmetric iterative allylchromation (Nozaki-Hiyama coupling),[2] allyltitanation,[3] allylstannation,[4] allylsilation,[5] and allylboration[6] have been employed in synthetic approaches to 1,3-diols and higher homologues. Brown’s allyl borane [Ipc2B(n-C3H5), Ipc = isopinocampheyl][7] has found the most extensive use in iterative asymmetric Carbonyl Allylation.[6] While superstoichiometric generation of isopinocampheol poses a barrier to large volume applications,[8] both enantiomers of α-pinene are available at low cost and excellent levels of stereocontrol are observed, making the Brown protocol an attractive method for the academic lab. However, use of traditional allylmetallation protocols in iterative two-directional syntheses of 1,3-polyol substructures is prohibited by the instability of malondialdehyde. In connection with efforts to exploit catalytic hydrogenation in C-C couplings beyond hydroformylation,[9] an enantioselective protocol for Carbonyl Allylation from the alcohol oxidation level was developed in our laboratory under the conditions of iridium catalyzed transfer hydrogenation employing allyl acetate as an allyl donor.[10] Here, the reactant alcohol serves dually as a source of hydrogen and as an aldehyde precursor, enabling formation of highly optically enriched homoallylic alcohols directly from the alcohol oxidation level by way of a transient aldehyde. Whereas reductive coupling of allylic carboxylates, alcohols, or ethers to Carbonyl partners is typically achieved using metallic reductants such as SmI2, SnCl2, Et2Zn or Et3B,[11–15] transfer hydrogenative Carbonyl Allylation precludes the use of any stoichiometric metallic reagents. Here, using a chiral iridium C,O-benzoate complex modified by 4-chloro-3-nitrobenzoic acid and (R)- or (S)-Cl,MeO-BIPHEP, we report an iterative two-directional bis-Allylation of glycols, as demonstrated by the rapid assembly of protected 1,3-polyol substructures with exceptional levels of enantiocontrol and catalyst-directed diastereoselectivity.[16] Notably, this process successfully exploits 1,3-diols as synthetic equivalents to unstable malondialdehydes. Although malondialdehyde can be generated through the hydrolysis of 1,1,3,3-tetramethoxypropane, capture of this dialdehyde is impeded by the fact that it is highly unstable and is generated in an aqueous environment, which promotes hydration, oligomerization, self-condensation, which precludes the use of many organometallic reagents. The ability to bypass stoichiometric pre-formation of aldehyde electrophiles, as in Carbonyl Allylation from the alcohol oxidation level, potentially enables Allylation processes that cannot be performed efficiently from preformed aldehyde precursors. We reasoned that 1,3-propanediol 1a could serve as a synthetic equivalent to malondialdehyde via successive generation and capture of mono-aldehyde intermediates. Accordingly, the asymmetric Allylation of propylene glycol 1a was explored. Beyond the variation of standard reaction parameters, our discovery that the active catalyst is an ortho-cyclometallated iridium C,O-benzoate[10b] offered further opportunity to enhance catalyst performance through structural modification of the benzoate. To our delight, using the cyclometallated catalyst generated in situ from [Ir(cod)Cl]2 (5 mol%), (S)-Cl,MeO-BIPHEP (10 mol%), 4-chloro-3-nitrobenzoic acid (20 mol%) and Cs2CO3 (40 mol%) in dioxane solvent (0.2 M), the coupling of allyl acetate (1000 mol%) to 1a at 90°C delivers the C2-symmetric homoallylic diol (S,S)-2a in 70% isolated yield and ≥ 99% enantiomeric excess with ≥ 30:1 diastereoselectivity, as determined by chiral stationary phase HPLC analysis. This transformation was reproducible on 20 mmol scale. A decrease in the loading of allyl acetate from 10 to 5 equivalents diminished the isolated yield of (S,S)-2a by only 8%. These conditions were applied to propylene glycols 1a–1e. Although yields were slightly diminished in the case of 2-methyl-1,3-propanediol 1b and 2,2-dimethyl-1,3-propanediol (neopentyl glycol) 1c, uniformly high levels of enantioselectivity were observed in all cases (≥99% ee), as the minor enantiomer of the intermediate mono-adduct is converted to the meso product. Efficient bis-Allylation of 2-methylene-1,3-propanediol 1e is especially remarkable in view of the exceptional instability anticipated for the corresponding dialdehyde, which, to our knowledge, has not been reported in the literature (Scheme 1). Scheme 1 Enantioselective Allylation of propylene glycols 1a–1e under the conditions of asymmetric C-C bond forming transfer hydrogenation.a The step economy associated with the double Allylation of propylene glycols is borne out by comparison to known methods for the synthesis of C2-symmetric homoallylic diols. For example, in the course of a synthetic approach to (+)-phorboxazole A, the mono-TBS-derivative of C2-symmetric diol (S,S)-2a was prepared in 7 steps from propylene glycol 1a (by way of the indicated aldehyde) through successive use of Brown’s reagent for asymmetric Carbonyl Allylation [Ipc2B(n-C3H5)].[6e] An improved protocol delivers (S,S)-2a in 4 steps from acetyl acetone.[17] Additionally, in the synthesis of pysmberin, the C2-symmetric diol (R,R)-2c was prepared in 5 steps from isobutyraldehyde (by way of the indicated aldehyde) through successive use Leighton’s reagent for asymmetric Carbonyl Allylation.[5a] Under the conditions of iridium catalyzed transfer hydrogenation, the parent C2-symmetric homoallylic diols (S,S)-2a and (R,R)-2c are prepared in highly optically enriched form in a single manipulation from propylene glycol and neopentyl glycol, respectively. To illustrate the utility of this methodology in the context of “two-directional chain synthesis,”[18] the C2-symmetric diol (S,S)-2a prepared from propylene glycol 1a was subjected to a second round of concomitant two-directional chain elongation. Accordingly, (S,S)-2a was converted to the corresponding acetonide in 91% isolated yield, which was subjected to ozonolysis. Upon complete consumption of starting material, as revealed by the persistence of a light blue color, the reaction mixture was treated with sodium borohydride to deliver the C2-symmetric diol (S,S)-3a in 89% isolated yield. Exposure of diol (S,S)-3a to the iridium catalyst modified by (R)-Cl,MeO-BIPHEP at 110 °C delivers the higher C2-symmetric diol (R,S,S,R)-4a in 74% isolated yield, accompanied by 16% of the corresponding mono-Allylation product. Using the enantiomeric catalyst modified by (S)-Cl,MeO-BIPHEP, (S,S,S,S)-4a is obtained in 81% isolated yield, accompanied by 12% of the corresponding mono-Allylation product. In both cases, diastereomeric bis-adducts could not be detected by 1H NMR analysis, signifying exceptional levels of catalyst directed diastereoselectivity.[16] The achiral iridium catalyst ligated by BIPHEP converts (S,S)-3a to a statistical mixture of diastereomeric adducts. The assembly of either (R,S,S,R)-4a or (S,S,S,S)-4a in merely four steps from propylene glycol illustrates the power of this protocol for iterative two-directional chain elongation (Scheme 2). Scheme 2 Enantiospecific two-directional chain elongation via transfer hydrogenative Carbonyl Allylation. Finally, the iridium catalyzed asymmetric transfer hydrogenative Allylation of higher glycols was explored. The outcome of such transformations was rendered uncertain, as 1,4-butanediol 1f and 1,5-pentanediol 1g are transformed to γ-butyrolactone and δ-valerolactone, respectively, under transfer hydrogenation conditions.[19] Remarkably, upon exposure to conditions for iridium catalyzed asymmetric transfer hydrogenative Allylation, 1,4-butanediol 1f and 1,5-pentanediol 1g are transformed to the corresponding the C2-symmetric diols (R,R)-2f and (R,R)-2g in 68% and 56% yields, respectively, as single diastereo- and enantiomers, as determined by chiral stationary phase HPLC analysis (Scheme 3). Scheme 3 Enantioselective Allylation of 1,4-butanediol 1f and 1,5-pentanediol 1g under the conditions of asymmetric C-C bond forming transfer hydrogenation.a In summary, under the conditions of iridium catalyzed C-C bond forming transfer hydrogenation, diverse glycols 1a–1g are subject to highly enantioselective Carbonyl Allylation from the alcohol oxidation level to furnish the corresponding C2-symmetric diols 2a–2g. The rapid assembly of 1,3-polyol substructures was demonstrated using iterative two-directional asymmetric Carbonyl Allylation from the alcohol oxidation level. Remarkably, the stereochemical bias of enantiomeric iridium catalysts modified by (R)-or (S)-Cl,MeO-BIPHEP was found to override the intrinsic diastereofacial bias of transient β-chiral aldehyde substrates, enabling generation of the acetonide protected C2-symmetric tetraols (R,S,S,R)-4a and (S,S,S,S)-4a as single stereoisomers in merely four steps from propylene glycol. Future studies will focus on the development of related C-C bond forming transfer hydrogenations, including imine additions from the amine oxidation level.