Chiral Boron Reagents Research Articles

Synthesis of proteasome inhibitor 6-deoxy-omuralide and its enantiomer using stereoselective alkylation of substituted proline ester.

A potent 20S proteasome inhibitor, 6-deoxy-omuralide was stereoselectively synthesized in 20 steps with 5.1% overall yield staring from a chiral boron agent and d-glyceraldehyde acetonide. The stereoselective alkylation of the substituted proline ester with 3-iodo-2-methylprop-1-ene served as the key step. The enantiomer of 6-deoxy-omuralide was achieved in 20 steps with 4.6% overall yield by just changing the chiral boron reagents in the first step. Our current work provides a flexible approach to 6-deoxy-omuralide and its enantiomer with the adornment at the C4 position.

Enantioselective Construction of Tertiary C–O Bond via Allylic Substitution of Vinylethylene Carbonates with Water and Alcohols

An efficient method for the enantioselective construction of tertiary C-O bond via asymmetric allylic substitution of racemic vinylethylene carbonates with water and alcohols has been developed. Under the cooperative catalysis system of an in situ generated chiral palladium complex and boron reagent in mild conditions, the process allowed rapid access to valuable tertiary alcohols and ethers in high yields with complete regioselectivities and high enantioselectivities. This protocol represented the first example of direct enantioselective formation of a tertiary C-O bond with water as an oxygen donor. The synthetic utilities of the process have been demonstrated by the elaboration of the products into key intermediates of biologically relevant agents, and chiral tertiary cyclic ethers could also be provided through the sequential reactions of the allylic etherification and ring-closing metathesis.

ChemInform Abstract: Chiral Lewis Acids in Catalytic Asymmetric Reactions

This review examines the recent advances in the use of chiral Lewis acids, usually generated in situ from a Lewis acid and a chiral auxiliary, in the Diels-Alder reaction, the ene reaction, the hydrocyanation of aldehydes, the ring-opening of epoxides and various miscellaneous reactions. Structural studies of the complex formed between carbonyl compounds and Lewis acids are also reported. The Sharpless epoxidation is not covered by this review. 1. Introduction 2. Asymmetric Diels-Alder Reactions 2.1. Chiral Titanium Reagents 2.2. Chiral Aluminum Reagents 2.3. Chiral Boron Reagents 2.4. Chiral Ruthenium Reagents 3. Asymmetric [2+2] Cycloaddition Reactions 4. Asymmetric Ene Reaction 5. Asymmetric Hydrocyanation of Aldehydes 6. Asymmetric Ring Opening of Epoxides 7. Miscellaneous Asymmetric Reactions 8. Structural Studies on the Complexes of Carbonyl Compounds and Lewis Acids

ChemInform Abstract: The Asymmetric Diels-Alder Reaction of α,β-Unsaturated Aldehydes with Dienes Using a Chiral Boron Reagent as a Catalyst.

The asymmetric Diels–Alder reaction of α,β-unsaturated aldehydes with cyclopentadiene is catalyzed by a novel chiral boron reagent generated in situ from boron tribromide and a chiral prolinol derivative, to afford the corresponding adducts in good yields with fairly good to excellent ees.

ChemInform Abstract: Asymmetric Aza-Diels-Alder Reaction Mediated by Chiral Boron Reagent.

An asymmetric aza-Diels-Alder reaction of an imines mediated by an in situ generated chiral boron complex is described. The method is successful with several aldimines and affords products of up to 9O% ee

New Approaches to Branched β-Amino α-Hydroxy Acids, Taxol Side-chain Analogs

Abstract The phenylisothreonine derivatives, taxol side-chain analogs, were synthesized by two routes, one based on the highly stereoselective addition of a phenyl Grignard reagent to the L-threose-derived nitrone 7, and the other using asymmetric α-alkoxyallylation of the ketimine 20 with chiral allyl boron reagents.

Studies on the Total Synthesis of Amphidinolide O (III): A Stereoselective Synthesis of C1-C11 Fragment

The amphidinolides were isolated from the marine dinoflagellate Amphidinium sp., which produces a host of secondary metabolites endowed with potent cytotoxicity against various cancer cell lines. Amphidinolide O (1) displayed potent in vitro cytotoxicity against L1210 marine leukemia cells and human epidermoid carcinoma KB cells with 1.7 and 3.6 μg/mL of IC50s, respectively. In addition to our recent reports regarding to the synthesis of C12-C17 and C3-C11 fragments of amphidinolide O (1), we describe herein a new route to diastereoselective synthesis of C1-C11 fragment of 1. The retrosynthetic analysis of 1 led to the C1-C11 fragment 2 and C12-C17 fragment 3 (Scheme 1). The hemiketal 2 was expected from acyclic precursor 4 which, in turn, would be derived by diastereoselective aldol reaction between ketone 5 and aldehyde 6. The C1-C6 fragment 8 (equivalent to 5 in scheme 1) was prepared as summarized below (Scheme 2). Enolization of carboximide 7 with Bu2BOTf and EtN(i-Pr)2 was followed by reaction with aldehyde to provide the syn-aldol product in 86% yield (ds = > 97 : 3 by H NMR analysis) (Scheme 2). The aldol product was treated with N,O-dimethylhydroxylamine hydrochloride and Al(Me)3 to provide the Weinreb amide in 91% yield. The free hydroxyl group was protected as PMB ether, and finally Weinreb amide was converted to ketone 8 in 85% yield by reaction with MeMgCl. Synthesis of C7-C11 fragment 10 (equivalent to 6 in scheme 1) was completed via 5-step sequences (Scheme 3). Monoprotection of propane-1,3-diol (9), Swern oxidation of the remaining alcohol to aldehyde, and Wittig-olefination was undertaken to give α,β-unsaturated ester, which was subsequently reduced by DIBAL and oxidized to provide the C7-C11 fragment 10, another key intermediate in the next aldol reaction. Aldol-reactions of fragments 8 and 10 were investigated with four chiral boron reagents in ether at −78 C (Scheme 4), and the use of chlorodicyclohexylborane provided the desired product with the best diastereoselectivity (11a : 11b = 67 : 33) in 61% (11a) and 30% (11b) yield, respectively. Hydroxyl group-directed 1,3-anti reduction of either 11a or 11b with NaBH(OAc)3 provided the 5,7-anti diol 12a or 12b in 91% yield. The (5R,7S)-isomer 12a was treated with 2,2-dimethoxypropane in the presence of PPTS (Scheme 5). The PMB-

Synthetic studies toward the total synthesis of tedanolide: assembly of the C1–C23 carbon backbone

A stereoselective assembly of the C1–C23 fragment representing the carbon backbone of tedanolide was accomplished utilizing a chiral boron reagent to effect the aldol coupling of the C1–C12 diketoester fragment with the C13–C23 aldehyde fragment.

Studies on the Total Synthesis of Amphidinolide O (II): A Stereoselective Synthesis of C1-C11 Fragment

The amphidinolides were isolated from the marine dinoflagellate Amphidinium sp., which produces a host of secondary metabolites endowed with potent cytotoxicity against various cancer cell lines. Amphidinolide O (1) displayed potent in vitro cytotoxicity against L1210 marine leukemia cells and human epidermoid carcinoma KB cells with 1.7 and 3.6 μg/mL of IC50s, respectively. In addition to our recent reports regarding to the synthesis of C12-C17 and C3-C11 fragments of amphidinolide O (1), we describe herein a new route to diastereoselective synthesis of C1-C11 fragment of 1. The retrosynthetic analysis of 1 led to the C1-C11 fragment 2 and C12-C17 fragment 3 (Scheme 1). The hemiketal 2 was expected from acyclic precursor 4 which, in turn, would be derived by diastereoselective aldol reaction between ketone 5 and aldehyde 6. The C1-C6 fragment 8 (equivalent to 5 in scheme 1) was prepared as summarized below (Scheme 2). Enolization of carboximide 7 with Bu2BOTf and EtN(i-Pr)2 was followed by reaction with aldehyde to provide the syn-aldol product in 86% yield (ds = > 97 : 3 by H NMR analysis) (Scheme 2). The aldol product was treated with N,O-dimethylhydroxylamine hydrochloride and Al(Me)3 to provide the Weinreb amide in 91% yield. The free hydroxyl group was protected as PMB ether, and finally Weinreb amide was converted to ketone 8 in 85% yield by reaction with MeMgCl. Synthesis of C7-C11 fragment 10 (equivalent to 6 in scheme 1) was completed via 5-step sequences (Scheme 3). Monoprotection of propane-1,3-diol (9), Swern oxidation of the remaining alcohol to aldehyde, and Wittig-olefination was undertaken to give α,β-unsaturated ester, which was subsequently reduced by DIBAL and oxidized to provide the C7-C11 fragment 10, another key intermediate in the next aldol reaction. Aldol-reactions of fragments 8 and 10 were investigated with four chiral boron reagents in ether at −78 C (Scheme 4), and the use of chlorodicyclohexylborane provided the desired product with the best diastereoselectivity (11a : 11b = 67 : 33) in 61% (11a) and 30% (11b) yield, respectively. Hydroxyl group-directed 1,3-anti reduction of either 11a or 11b with NaBH(OAc)3 provided the 5,7-anti diol 12a or 12b in 91% yield. The (5R,7S)-isomer 12a was treated with 2,2-dimethoxypropane in the presence of PPTS (Scheme 5). The PMB-

Enantioselective Claisen rearrangement of difluorovinyl allyl ethers

The enantioselective Claisen rearrangement of difluorovinyl allyl ethers was achieved, for the first time, in moderate to good enantioselectivity using a chiral boron reagent as the Lewis acid.

Enantioselective aromatic Claisen rearrangement

The development of a highly enantioselective aromatic Claisen rearrangement was achieved by the reaction of catechol mono allylic ethers with chiral boron reagent 1. This system was also shown to avoid the formation of para rearrangement and abnormal Claisen rearrangement products.

Practical preparation of α-hydroxy-β-amino ester units; Stereoselective synthesis of taxol side chain and norstatine

An asymmetric reaction of chiral imines with α-silyloxy ketene acetals mediated by chiral boron reagents is described. The key to its success is the use of the chiral boron complex prepared in situ from ( R)- or ( S)-binaphthol and B(OPh) 3. Both diastereomers of α-hydroxy-β-amino ester units are successfully prepared with high selectivities by the chiral boron reagents depending on the geometry of the silyl ketene acetals. The optically pure anti α-hydroxy-β-amino ester is obtained from ( E)-silyl ketene acetal, while the corresponding syn α-hydroxy-β-amino ester is obtained from (Z)-silyl ketene acetal. The method can be efficiently applied to the stereoselective synthesis of taxol C-13 side chain and the norstatine family.

Asymmetric aza-Diels-Alder reaction mediated by chiral boron reagent

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAsymmetric aza-Diels-Alder reaction mediated by chiral boron reagentKouji Hattori and Hisashi YamamotoCite this: J. Org. Chem. 1992, 57, 12, 3264–3265Publication Date (Print):June 1, 1992Publication History Published online1 May 2002Published inissue 1 June 1992https://doi.org/10.1021/jo00038a003RIGHTS & PERMISSIONSArticle Views965Altmetric-Citations126LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (271 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Studies in macrolide synthesis: A stereocontrolled synthesis of a (9 S)-macrolide intermediate for oleandomycin using chiral boron reagents.

The (9 S)-macrolide 1 (P = TBS) was prepared in 14 steps (5% yield) with 63% overall ds starting from the ethyl ketone ( S)- 2. The C 1–C 7 and C 8–C 13 segments, 3 and 4, were obtained via boron enolate aldol reactions mediated by (+)- and (−)-(Ipc) 2BOTf, respectively.

The Asymmetric Diels–Alder Reaction of α,β-Unsaturated Aldehydes with Dienes Using a Chiral Boron Reagent as a Catalyst

Abstract The asymmetric Diels–Alder reaction of α,β-unsaturated aldehydes with cyclopentadiene is catalyzed by a novel chiral boron reagent generated in situ from boron tribromide and a chiral prolinol derivative, to afford the corresponding adducts in good yields with fairly good to excellent ees.

Asymmetric aldol reactions using chiral boron reagents: Application to the synthesis of tirandamycin A

The bicyclic acetal 1, a key intermediate in previous synthetic studies on tirandamycin A, has been prepared in enantiomerically pure form starting from the ( R )-ethylketone 2 and the aldehyde 3. A reagent controlled aldol reaction using (-)-(Ipc) 2BOTf selectively gave the 1,2- syn–2,4- syn adduct 4, which was subsequently converted into 1 via the 1,3- anti diol 5.

Chiral Lewis Acids in Catalytic Asymmetric Reactions

This review examines the recent advances in the use of chiral Lewis acids, usually generated in situ from a Lewis acid and a chiral auxiliary, in the Diels-Alder reaction, the ene reaction, the hydrocyanation of aldehydes, the ring-opening of epoxides and various miscellaneous reactions. Structural studies of the complex formed between carbonyl compounds and Lewis acids are also reported. The Sharpless epoxidation is not covered by this review. 1. Introduction 2. Asymmetric Diels-Alder Reactions 2.1. Chiral Titanium Reagents 2.2. Chiral Aluminum Reagents 2.3. Chiral Boron Reagents 2.4. Chiral Ruthenium Reagents 3. Asymmetric [2+2] Cycloaddition Reactions 4. Asymmetric Ene Reaction 5. Asymmetric Hydrocyanation of Aldehydes 6. Asymmetric Ring Opening of Epoxides 7. Miscellaneous Asymmetric Reactions 8. Structural Studies on the Complexes of Carbonyl Compounds and Lewis Acids

ChemInform Abstract: Aldol Reactions of Methyl Ketones Using Chiral Boron Reagents: A Reversal in Aldehyde Enantioface Selectivity.

AbstractAcetone (I) and its substituted derivatives (IV) are subjected to selective enolization with a chiral borinate in the presence of di(isopropyl)ethylamine and subsequent coupling with the aldehydes (II), yielding the hydroxy ketones (+)‐(III) or (+)‐(V) as the main products.

ChemInform Abstract: A Short Asymmetric Synthesis of a C19‐C27 Segment (V) of Rifamycin S. Kinetic Resolution in the Aldol Reactions of Ethyl Ketones (.+‐.)‐(I) Using Chiral Boron Reagents.

ChemInform Abstract: A Short Asymmetric Synthesis of a C19‐C27 Segment (V) of Rifamycin S. Kinetic Resolution in the Aldol Reactions of Ethyl Ketones (.+‐.)‐(I) Using Chiral Boron Reagents.

A short asymmetric synthesis of a C19–C27 segment of rifamycin S. Kinetic resolution in the aldol reactions of ethylketones using chiral boron reagents

The chiral reagents (+)- and (−)-(Ipc)2BOTf are used to control the aldol addition reactions of ethylketone3 with methacrolein. Under suitable conditions, racemic3 can be converted into the SS aldol adduct (+)-4 in ≥95% ee with >95% diastereoselectivity. Resolved starting ketone (+)-3 can be recovered in ≥95% ee. Adduct (+)-4 was converted into the rifamycin S segment (−)-2via stereoselective ketone reduction and hydroboration.