Hydroboration-oxidation Research Articles

Aza-Wittig Rearrangements of N-Benzyl and N-Allyl Glycine Methyl Esters. Discovery of a Surprising Cascade Aza-Wittig Rearrangement/Hydroboration Reaction.

Treatment of N-(arylmethyl)-N-aryl or N-allyl-N-aryl glycine methyl ester derivatives with (n)Bu2BOTf and (i)Pr2NEt effects an aza-Wittig rearrangement that provides N-aryl phenylalanine methyl ester derivatives and N-aryl allylglycine methyl ester derivatives, respectively, in good yield with moderate to good diastereoselectivity. Under similar conditions, analogous substrates bearing N-carbonyl groups are converted to 1,4,2-oxazaborole derivatives. Additionally, N-allyl-N-aryl glycine methyl ester derivatives subjected to similar conditions at elevated temperatures undergo an aza-[2,3]-Wittig rearrangement, followed by a subsequent hydroboration oxidation reaction, to afford substituted amino alcohol products.

Hydroboration–oxidation: A chemoselective route to cellulose ω-hydroxyalkanoate esters

We describe the first synthesis of hydroxy-functionalized polysaccharide esters via chemoselective olefin hydroboration–oxidation in the presence of ester groups. Cellulose esters with terminally olefinic side chains were first synthesized by esterification of commercially available cellulose esters (e.g., cellulose acetate) with undec-10-enoyl chloride or pent-4-enoyl chloride. Subsequent two-step, one-pot hydroboration–oxidation reactions of the cellulose esters were performed, using 9-borabicyclo[3.3.1]nonane as hydroboration agent, followed by oxidizing the intermediate borane to a hydroxyl group using mildly alkaline H2O2. Sodium acetate was used as a weak base to catalyze the oxidation, thereby minimizing undesired ester hydrolysis. Characterization methods including FTIR, 1H, and 13C NMR proved the selectivity of the hydroboration–oxidation pathway, providing a family of novel cellulose ω-hydroxyalkanoyl esters that were previously difficult to access.

Formal Total Synthesis of Stevastelins B and B3

AbstractThe formal total synthesis of stevastelins B and B3 (2 and 4, resp.) have been accomplished employing a highly enantiomerically controlled Lewis acid catalyzed non‐aldol approach to obtain the syn aldol product and temperature controlled hydroboration oxidation reaction to construct four consecutive stereogenic centers. The other key reactions include Sharpless asymmetric epoxidation, macrolactonization, and macrolactamization towards building the core skeleton 2 and 4.

A cyclopropanol-based approach to synthesis of Unit A of the cryptophycins

A new asymmetric synthesis of Unit A of the cryptophycins has been carried out yielding 13% of the target product over 14 steps. The key steps of the synthesis were diastereoselective hydroboration–oxidation reactions performed on the alkenyl moiety of a 1,3-dioxane derivative 8, which can be easily prepared via the Kulinkovich cyclopropanation of protected diethyl (S)-(−)-malate followed by transformation of the resulting small rings of the product 6 into the functional groups necessary for the synthesis of the target compound.

ChemInform Abstract: Stereoselective Synthesis of (‐)‐Lepadins A—C.

A concise synthesis of the marine alkaloids (−)-lepadins A–C from a phenylglycinol-derived tricyclic lactam is reported. Key steps from the stereochemical standpoint involve stereoselective cyclocondensation, double bond hydrogenation, oxazolidine opening, hydroboration–oxidation, and Horner–Wadsworth–Emmons reactions.

Stereoselective synthesis of β-d-GlcNAc-(1 → 4)-d-Glc disaccharide starting from lactose

The stereoselective preparation of the β-d-GlcNAc-(1→4)-d-Glc disaccharide starting from known 4-O-[6-O-(1-methoxy-1-methylethyl)-3,4-O-isopropylidene-β-d-talopyranosyl]-2,3:5,6-di-O-isopropylidene-aldehydo-d-glucose dimethyl acetal (2), in turn easily obtained from lactose, is reported. Key steps of this new procedure, that avoids the glycosylation reaction, are (a) a first epimerization at C-4′ through an unusual procedure involving a completely stereospecific hydroboration–oxidation of the enol ether group of the hex-4-enopyranoside 4, obtained from 3 by base promoted acetone elimination, (b) an amination with inversion by SN2 reaction on an imidazylate intermediate, and, finally, (c) N-acetylation followed by complete deprotection.

Hydroboration of unsaturated fatty acid methyl esters and conversion of the boron adducts*

Unsaturated FAMEs can be modified to higher value compounds by hydroboration of the double bond. The added boron atom can be replaced in a subsequent oxidation by a hydroxy group. This way methyl 10‐undecenoate (1b), methyl oleate (3a), methyl ricinoleate ((9Z,12R)‐6a), and methyl linoleate (9) were converted into methyl 11‐hydroxyundecanoate and methyl hydroxyoctadecanoates in 82–92% yield. Organoboranes isomerize at higher temperatures. Hydroboration of oleic acid and subsequent heating to 220°C led after oxidative work‐up to 70% of 1,4‐octadecanediol. Presumably a 1,4‐oxaborinane intermediate is involved. Alkyl groups of organoboranes can be attached to the carbonyl‐equivalent: dichloromethyl methyl ether (DCME). With this reaction the boranes of the esters 1b and 3a were converted in 55–80% yield to dimers with an inserted ketocarbonyl group. Ester 9 afforded in the same reaction methyl nonadecanoates with an integrated cyclopentene ring.Practical applications: Hydroboration–oxidation allows the partially regioselective conversion of unsaturated FAMEs into hydroxy‐ and dihydroxyesters. Thermal isomerization of the boranes from methyl oleate, oleic acid, and oleyl alcohol leads after oxidative work‐up to the 1,4‐diol: 1,4‐octadecanediol as main product. These products are useful as components for polyesters, polyurethanes, and precursors for heterocycles. Reaction of organoboranes from unsaturated FAMEs with the carbonyl equivalent: DCME provides a one‐step access to 1,ω‐diesters with an internal keto group, which can be applied for coupling, cross‐linking, and further conversion. The borane · THF complex is commercially available in amounts of 0.8 mol and more to do exploratory research toward such applications.

Polyisobutylene-Based Helical Block Copolymers with pH-Responsive Cationic Side-Chain Amino Acid Moieties by Tandem Living Polymerizations

Syntheses of diblock copolymers of isobutylene (IB) with amino acid-based monomers were carried out by a combination of living carbocationic and reversible addition–fragmentation chain transfer (RAFT) polymerizations. Cationic polymerization of IB followed by hydroboration oxidation produced hydroxyl end-capped polyisobutylene, which was subsequently converted into macro-chain-transfer agent (macro-CTA) for the RAFT polymerization of tert-butyloxycarbonyl (Boc)-protected amino acid-based monomers such as Boc-l-alanine methacryloyloxyethyl ester (Boc-l-Ala-HEMA) and Boc-l-leucine methacryloyloxyethyl ester (Boc-l-Leu-HEMA). The block length and molecular weight could be controlled while maintaining a narrow molecular weight distribution. These block copolymers form core–shell type micellar structure in methanol—a good solvent for side-chain amino acid block but bad solvent for polyisobutylene segment. Specific rotation and circular dichroism (CD) studies indicated the chiral nature of the block copolymers ...

Synthesis of Glycerol Homologues

A series of monoprotected glycerol homologues and triols were prepared in high overall yields (>90%) via the hydroboration–oxidation of the corresponding dienols. Hydroboration with disiamylborane and concomitant alkaline oxidation (NaOH, H 2 O 2 ) was found to be a mild, high-yielding, and highly efficient method for the construction of a variety of glycerol homologues.

Synthesis and Spectral Properties of Porphyrin-Cored Arylether Dendrimers with Hydroxy Peripheral Groups

Free base porphyrin-cored arylether dendrimers 2a~2c with terminal hydroxy groups in the periphery have been successfully prepared by hydroboration-oxidation reaction of corresponding 1a~1c with terminal vinyl groups in the periphery. Their zinc derivatives Zn-2a~Zn-2c have also been prepared. Absorption and fluorescence properties of 2a~2c and Zn-2a~Zn-2c with peripheral hydroxy groups were affected more by dendritic environments than 1a~1c and Zn- 1a~Zn-1c with peripheral vinyl groups.

Synthesis and pharmacological investigation of new N-hydroxyalkyl-2-aminophenothiazines exhibiting marked MDR inhibitory effect

Novel N-hydroxyalkyl-2-aminophenothiazines implying a tetrazole moiety at the alkyl chain have been synthesized by hydroboration–oxidation of dienes followed by Buchwald–Hartwig cross-coupling reaction. Also, some sulfoxide and sulfone derivatives have been prepared by selective oxidations. MDR inhibition studies on rat hepatocyte cell culture revealed that some derivatives exhibit marked biological efficacy exceeding that of the standard verapamil (e.g., 3h, 4h, 16). Selected derivatives were subjected to chemical resolution to provide both enantiomers which were shown of similar activity on P-gp interaction measurements. The new compounds exhibited no toxicity.

Synthesis of Octopus Type Trimethylene Glycol β-D-glucopyranosides

ABSTRACT The octopus type oligo-hydroxypropylene glycol β-D-glucopyranosides were successfully synthesized in this studies: the sterospecific compound of allyl 2, 3, 4, 6-tetra-O-acetyl-β-D-glucopyranosides (1) was deacetylated with NaOMe in MeOH lead to allyl-β-D-glucopyranoside (2) which was perallylated and followed by hydroboration and subsequent oxidation afforded (3-hydroxy-propyl) 2, 3, 4, 6-tetraO(3-hydroxy-propyl)- β-D-glucopyranoside (4). As a result, not only allylpropylene glycol β-D-glucopyranosides (5, 7, and 9) but also hydroxypropylene glycol β-D-glucopyranosides (6, 8, and 10) were synthesized by repeated sequential perallylation followed by hydroboration/oxidation. Keywords : hydroboration/oxidation, perallylation, oligo-hydroxypropylene glycol β-D-glucopyranosides 1. INTRODUCTION Carbohydrates are naturally occurring abund-ant compounds that have been widely studied for a plethora of applications (Hanessian, 1983; Scott, 1994; Middleton et al., 1993). Of parti-cular interest has been their use as polyfunctional molecules for the design and/or synthesis of car-bohydrate-centered multivalent glycoclusters and glycodendrimers (Lindhorst et al., 1998; Lind-horst et al., 2001; Lindhorst et al., 2006). Most of them are based on a multi-step synthesis con-sisting of oligo-glycosylation in order to achieve a uniform O-hydroxy-spacer, such as ethylene or propylene glycol not only in the 2, 3, 4, 6-tetra hydroxy groups but also at the α-anomeric po-sition, turning them into carbohydrate-centered cluster glycosides (Lindhorst et al., 1998; Lind-horst et al., 2001; Lindhorst et al., 2006).Thus, it became our goal to attempt the syn-thesis of the exhaustive glycosylation of octopus type β-D-glucopyranosides. This could provide us with a great potential opportunity of a novel class of high-molecular weight monosaccharide mimetics, which could possibly be adapted for the generation of various spacers with different

Total synthesis of d-fagomine and 6-deoxyfagomine

Total synthesis of d-fagomine and 6-deoxyfagomine from readily available d-lyxose is described. The key steps included regioselective and diastereoselective amination, hydroboration–oxidation, and Appel reaction. The reaction of 3,4-anti-tribenzyl ether with chlorosulfonyl isocyanate in toluene at 0 °C afforded 3,4-anti-amino alcohol, an essential compound for the preparation of d-fagomine and 6-deoxyfagomine, with a high diastereoselectivity (dr=26:1) in 74% yield. The origin of diastereoselectivity can be explained by the neighboring group effect, which leads to retention of the stereochemistry.

An improved and efficient synthesis for IPL576,092 and its analogues

An improved and efficient preparation of IPL576,092 was developed. The synthetic route involves selective allylic oxidation of ∆5-sterols and subsequent hydroboration–oxidation as the key steps. In addition, two analogues were readily synthesized from commercially available steroidal compounds in two steps in the same way.

Synthesis of (±)-pterosin A via Suzuki–Miyaura cross-coupling reaction

A practical synthesis of (±)-pterosin A from commercially available 2-bromo-1,3-dimethyl-benzene 5 has been accomplished in 10% overall yield. The synthesis used Suzuki–Miyaura coupling reaction of C6-bromoindanone derivative 3 with potassium vinyltrifluoroborate 9, which provided the corresponding vinylindanone 2 in >85% yield. The vinylindanone 2 could be further elaborated to pterosin A by reduction with LAH, selective protection of primary alcohol with TESCl, hydroboration–oxidation of vinyl group, protection of primary alcohol with TIPSCl, oxidation of the secondary alcohol, and desilylation with TBAF.

Synthesis of C(27)–C(38) fragment of aflastatin A

Efforts at finding out a strategy for the synthesis of the densely hydroxylated C(27)–C(48) fragment of aflastatin A have been described. The initial studies dealing with alkyne–epoxide coupling using a linear polyol epoxide resulted in a debenzylative cycloetherification leading to a C-arabinoside derivative. This problem has been addressed by applying an epoxide pendant on a furanosyl unit. With the model alkyne, the epoxide–alkyne coupling proceeded smoothly. Subsequently, following a sequence of [Pd]-mediated alkynone cycloisomerization/stereoselective hydroboration–oxidation, the synthesis of the central C(27)–C(38) fragment has been executed. When employed, the original C(33)–C(48) alkyne, the coupling and the cycloisomerizations are facile. However, the resulting glycals are unstable, thus warranting a revision in our approach.

Serine Protease Inhibition by a Silanediol Peptidomimetic

Silanediol peptidomimetics are demonstrated to inhibit a serine protease. Asymmetric synthesis of the inhibitor was accomplished using Brown hydroboration and CBS reduction of an acylsilane intermediate. The silanediol product was found to inhibit the serine protease chymotrypsin with a K(i) of 107 nM. Inhibition of the enzyme may involve exchange of a silane hydroxyl with the active site serine nucleophile, contrasting with previous silanediol protease inhibitors.

ChemInform Abstract: Asymmetric Synthesis of 2‐Propylisofagomine Using Allylic Hydroxy Group Accelerated Ring‐Closing Enyne Metathesis.

Abstract2‐Propylisofagomine (XIV) is prepared via a diastereoselective vinylation of aldehyde (IV), a ring‐closing metathesis of the resulting enyne (VI), and a stereoselective hydroboration—oxidation of alkene (XI) as key steps.

Synthesis of novel H-shaped chromophores

A series of H-shaped chromophores with two parallel and non-conjugated D-π-A units have been synthesized, in which a 9,10-dihydroanthracene was employed as molecular backbone. The synthesis of these H-shaped chromophores 9a–11a was accomplished via an eight-step reaction, including double Claisen rearrangement, hydroboration–oxidation, Rieche formylation reaction, Knoevenagel condensation and Corey–Fuchs reaction, with a total yield about 12.5%. The corresponding mono-D-π-A unit compounds 9b–11b were also prepared in a similar procedure for the purpose of comparison. Crystal structures of three intermediates 5a, 7a and 8a were measured, which demonstrate that the two D-π-A units in a single H-shaped chromophore molecule are nearly arranged at the same direction. The studies of UV–vis spectra and the solvatochromic method indicate that the molecular second-order polarizabilities values (μβ) of H-shaped chromophores are remarkably increased compared with the corresponding mono-D-π-A unit reference compounds, without causing a large shift of the absorption band to longer wavelength.

Regioselective allylation of cyclomaltoheptaose (β-cyclodextrin) leading to per(2,6-di- O-hydroxypropyl-3- O-methyl)-β-cyclodextrin

The selective modification of cyclodextrins remains a real challenge to obtain well-defined structures. The targeted cycloheptakis-(1→4)-2,6-di- O-hydroxypropyl-3- O-methyl-α- d-glucopyranosyl [per(2,6-di- O-hydroxypropyl-3- O-methyl)-β-CD] was obtained by a three-step procedure. The selective allylation of the hydroxyl functions at the positions 2 and 6 was used as a first step. This reaction was revisited then enlarged to α and γ-CDs to determine new conditions for a one-step synthesis in high yield. The per(2,6-di- O-allyl)-β-CD derivative was then reacted with iodomethane to provide per(2,6-di- O-allyl-3- O-methyl)-β-CD. Oxidative hydroboration of the allyl functions was then carried out in order to obtain a new CD derivative with seven primary hydroxyl functions on each side of the truncated cone, having a similar reactivity.