Two-carbon Homologation Research Articles

A Chemoenzymatic Total Synthesis of the Phytotoxic Undecenolide (‐)‐Cladospolide A.

An eleven-step synthesis of the title compound (1) from biocatalytically-derived and enantiomerically pure ‘building blocks’ alcohol (R)-(−)-9 and ester 13 is described. Attempts to construct the twelve-membered lactone ring of cladospolide A in a direct manner by using a ring-closing metathesis (RCM) reaction failed. However, a ten-membered lactone, 19, could be constructed by such means and this was then subject to a two-carbon homologation sequence involving, inter alia, Wadsworth–Horner–Emmons and Yamaguchi lactonisation reactions in the closing stages of the synthesis. The impact of substituent stereochemistries and protecting groups on the RCM reaction leading to various ten-membered lactones is also described.

A Novel Two‐Carbon Homologation with N‐Vinylacetamides and Ethyl Vinyl Ether as Acetaldehyde Anion Equivalents in the Synthesis of 9H‐Xanthene, 9H‐Thioxanthene, and 9,10‐Dihydro‐9‐acridine Carboxaldehydes.

ChemInformVolume 35, Issue 20 Preparative Organic Chemistry A Novel Two-Carbon Homologation with N-Vinylacetamides and Ethyl Vinyl Ether as Acetaldehyde Anion Equivalents in the Synthesis of 9H-Xanthene, 9H-Thioxanthene, and 9,10-Dihydro-9-acridine Carboxaldehydes. Mahavir Prashad, Mahavir Prashad Process Res. Dev., Chem. Anal. Dev., Novartis Pharm. Corp., East Hanover, NJ 07936, USASearch for more papers by this authorYansong Lu, Yansong Lu Process Res. Dev., Chem. Anal. Dev., Novartis Pharm. Corp., East Hanover, NJ 07936, USASearch for more papers by this authorOljan Repic, Oljan Repic Process Res. Dev., Chem. Anal. Dev., Novartis Pharm. Corp., East Hanover, NJ 07936, USASearch for more papers by this author Mahavir Prashad, Mahavir Prashad Process Res. Dev., Chem. Anal. Dev., Novartis Pharm. Corp., East Hanover, NJ 07936, USASearch for more papers by this authorYansong Lu, Yansong Lu Process Res. Dev., Chem. Anal. Dev., Novartis Pharm. Corp., East Hanover, NJ 07936, USASearch for more papers by this authorOljan Repic, Oljan Repic Process Res. Dev., Chem. Anal. Dev., Novartis Pharm. Corp., East Hanover, NJ 07936, USASearch for more papers by this author First published: 21 April 2004 https://doi.org/10.1002/chin.200420052Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume35, Issue20May 18, 2004 RelatedInformation

On the paradox of TiCl 4 reducing power: pinacol coupling and two-carbon homologation of carbonyl compounds

TiCl 4/DIPEA/CH 2Cl 2 reducing system promotes pinacol coupling and/or reduction to alcohol of aromatic aldehydes and carbonyl compounds activated towards reduction by an electron withdrawing group. In addition, bis homologation of these substrates is observed. An inner-sphere electron transfer from TiCl 4 to DIPEA accounts for the products distribution.

A chemoenzymatic total synthesis of the phytotoxic undecenolide (-)-cladospolide A.

An eleven-step synthesis of the title compound (1) from biocatalytically-derived and enantiomerically pure 'building blocks' alcohol (R)-(-)-9 and ester 13 is described. Attempts to construct the twelve-membered lactone ring of cladospolide A in a direct manner by using a ring-closing metathesis (RCM) reaction failed. However, a ten-membered lactone 19, could be constructed by such means and this was then subject to a two-carbon homologation sequence involving, inter alia, Wadsworth-Horner-Emmons and Yamaguchi lactonisation reactions in the closing stages of the synthesis. The impact of substituent stereochemistries and protecting groups on the RCM reaction leading to various ten-membered lactones is also described.

A novel two-carbon homologation with N-vinylacetamides and ethyl vinyl ether as acetaldehyde anion equivalents in the synthesis of 9H-xanthene, 9H-thioxanthene, and 9,10-dihydro-9-acridine carboxaldehydes.

An efficient synthesis of 9H-xanthene-9-carboxaldehyde (3a), 9H-thioxanthene-9-carboxaldehyde (3b), and 9,10-dihydro-10-methyl-9-acridinecarboxaldehyde (3c) by a novel two-carbon homologation of xanthydrol (1a), thioxanthydrol (1b), and 9,10-dihydro-10-methyl-9-acridinol (1c), respectively, using N-vinylacetamides (2a,b) or ethyl vinyl ether (2c) as acetaldehyde anion equivalents, is described.

Stereoselective Synthesis of Spicigerolide.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Stereoselective synthesis of spicigerolide

The first total synthesis of the naturally occurring, cytotoxic lactone spicigerolide is described. The commercially available sugar l-rhamnose was the chiral starting materal. Key steps in the synthesis were an aldehyde two-carbon homologation via the Corey–Fuchs protocol, an asymmetric Brown-type aldehyde allylation and a ring-closing metathesis.

Titanocene(II)‐Promoted Reactions of Thioacetals with Ethylene: Selective Formation of Terminal Olefins with One‐ or Two‐Carbon Homologation.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Titanocene(II)-promoted reactions of thioacetals with ethylene: selective formation of terminal olefins with one- or two-carbon homologation

Thioacetals are selectively transformed into two types of terminal olefins, one with one-carbon homologation and the other with two-carbon homologation, by treatment with a titanocene(II) species under ethylene. The mode of the reaction is controlled by changing the ligands coordinated to titanocene(II).

Two-carbon homologation of aldehydes via silyl ketene acetals. 2. Study of the stereochemical control in the formation of (E)-alkenoic acids.

The condensation of C,O,O-tris(trimethylsilyl)ketene acetal 1 with aldehydes 2 in the presence of catalytic amounts of mercuric iodide at room temperature affords syn and anti beta-trimethylsiloxy alpha-trimethylsilyl alkanoic acid silyl esters 3 in good yields. These new compounds gave, under acidic or basic conditions, E and (or) Z enoic acids 4. The paths for the formation of these alkenoic acids are discussed.

Total synthesis of rutamycin B and oligomycin C.

The asymmetric synthesis of the macrolide antibiotics (+)-rutamycin B (1) and (+)-oligomycin C (2) is described. The approach relied on the synthesis and coupling of the individual spiroketal fragments 3a and 3b with the C1-C17 polyproprionate fragment 4. The preparation of the spiroketal fragments was achieved using chiral (E)-crotylsilane bond construction methodology, which allowed the introduction of the stereogenic centers prior to spiroketalization. The present work details the synthesis of the C19-C28 and C29-C34 subunits as well as their convergent assembly through an alkylation reaction of the lithiated N,N-dimethylhydrazones 6 and 8 to afford the individual linear spiroketal intermediates 5a and 5b, respectively. After functional group adjustment, these advanced intermediates were cyclized to their respective spiroketal-coupling partners 40 and 41. The requisite polypropionate fragment was assembled in a convergent manner using asymmetric crotylation methodology for the introduction of six of the nine-stereogenic centers. The use of three consecutive crotylation reactions was used for the construction of the C3-C12 subunit 32. A Mukaiyama-type aldol reaction of 35 with the chiral alpha-methyl aldehyde 39 was used for the introduction of the C12-C13 stereocenters. This anti aldol finished the construction of the C3-C17 advanced intermediate 36. A two-carbon homologation completed the construction of the polypropionate fragment 38. The completion of the synthesis of the two macrolide antibiotics was accomplished by the union of two principal fragments that was achieved with an intermolecular palladium-(0) catalyzed cross-coupling reaction between the terminal vinylstannanes of the individual spiroketals 3a and 3b and the polypropionate fragment 4. The individual carboxylic acids 46 and 47 were cyclized to their respective macrocyclic lactones 48 and 49 under Yamaguchi reaction conditions. Deprotection of these macrolides completed the synthesis of the rutamycin B and oligomycin C.

A Common Approach to the Synthesis of Monocyclofarnesyl Sesquiterpenes

3b-hydroxy-4,4,10b-trimethyl-9-decalone and its dehydroxy analogue are useful intermediates whose Baeyer-Villiger oxidation and subsequent two-carbon homologation provides a quick entry into the monocyclofarnesyl skeleton. The synthetic approaches to a variety of sesquiterpenes are discussed.

Synthesis of curacin A, an antimitotic cyclopropane-thiazoline from the marine cyanobacterium Lyngbya majuscula

Charette asymmetric cyclopropanation, chiral thiazoline synthesis by thioamide cyclization under modified Mitsunobu conditions, Ti( iPrO) 4/bi-naphthol catalyzed allylstannane addition, and an exceptionally mild two-carbon homologation via dehydrative alkylation with phenylsulfonylacetonitrile/Ph 3P/ADDP convened in an efficient, stereocontrolled route to the title bioactive heterocycle.

A Pummerer-Type Novel Ring Fission of 2-Methylsulfinyl-5,6-dihydro-4H-1,3,4-thiadiazine Derivatives: A Homologation of Aldehydes and Ketones

Abstract Aldehydes and ketones were converted into 2-methylsulfinyl-5,6-dihydro-4H-1,3,4-thiadiazines via the formation and base-induced ring-closure of N-alkylidene-N′-bis(alkylthio)methylenehydrazines followed by mCPBA oxidation. The subsequent Pummerer-type ring fission of the rings was performed by treating with trifluoroacetic anhydride or trifluoromethanesulfonic anhydride at −78 °C to give α,β-unsaturated esters and ketones in modest yields. Thus, this reaction sequence was regarded as being a new method for the two-carbon homologation of aldehydes and ketones.

Two-Carbon Homologation of Grignard Reagents to Primary Amines

Two-Carbon Homologation of Grignard Reagents to Primary Amines

A convenient method for the preparation of hapten phosphoramidites.

Automated incorporation of haptens at the 3' or 5' end of oligonucleotides required the preparation of the corresponding hapten phosphoramidites. The requisite 1,3-diol framework was prepared in two steps from a carboxylic acid precursor first by a two-carbon homologation using Meldrum's acid to form the corresponding 3-oxo ester and then subsequent reduction to the diol. The primary alcohol was protected with a dimethoxytrityl group, while the secondary alcohol was converted to the reactive phosphoramidite.

A Homologation of Aldehydes and Ketones via the Formation and the Subsequent Pummerer-type Ring Fission of 2-Methylsulfinyl-5,6-dihydro-4H-1,3,4-thiadiazine Derivatives

Abstract A two-carbon homologation of aldehydes and ketones was achieved by using a sequence involving the formation and the subsequent Pummerer-type ring fission of 5,6-dihydro-4H-1,3,4-thiadiazine rings possessing methylsulfinyl functionality at C-2.

Two-Carbon Homologation of Aldehydes. Synthesis of trans-α, β-Unsaturated Aldehydes

2-tri- n -Butylstannylvinyl ethers are useful synthetic equivalents of acetaldehyde in 2-carbon homologation reactions. When reacted with aldehydes in the presence of BF 3 ·OEt 2 the corresponding trans - α , β -unsaturated aldehydes are obtained in high yield. Reactions of 2-tri- n -butylstannyl vinnyl ethers with aldehydes in the presence of BF 3 ·OEt 2 led to trans- α, β-unsaturated aldehydes.

Two-carbon homologation of aldehydes. Synthesis of trans-α,β-unsaturated aldehydes

2-tri-n-Butylstannylvinyl ethers are useful synthetic equivalents of acetaldehyde in 2-carbon homologation reactions. When reacted with aldehydes in the presence of BF3·OEt2 the corresponding trans-α,β-unsaturated aldehydes are obtained in high yield.

ChemInform Abstract: An Effective Synthesis of 2,2‐Difluoro‐3‐hydroxy Esters.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.