Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

• Oliver Ries,
• Martin Büschleb,
• Markus Granitzka,
• Dietmar Stalke and
• Christian Ducho

Beilstein J. Org. Chem. 2014, 10, 1135–1142, doi:10.3762/bjoc.10.113

• protecting group pattern. The most promising strategy to achieve these goals appeared to be a variation of the ex-chiral pool synthesis developed by Zhu and co-workers [32]. They have utilized the stereocenter of D-serine in a diastereoselective Grignard addition to protected D-serinal as the key step of

• derivative with limited stability, which was immediately converted into alcohol 4 by diastereoselective Felkin–Anh type Grignard addition with isopropyl magnesium chloride (50% yield over 2 steps from 3, dr > 95:5). However, we could not confirm that the use of diethyl ether as co-solvent in the Grignard

• and Grignard addition. The enantiomeric purity of reisolated 3 was determined by HPLC analysis as its racemization can readily occur via silyl migration under the basic reaction conditions (see Supporting Information File 2 for HPLC chromatograms and for the synthesis of the racemic reference). After

Phosphinate-containing heterocycles: A mini-review

• Olivier Berger and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2014, 10, 732–740, doi:10.3762/bjoc.10.67

• this work, they obtained 11 different compounds in yields up to 100% and diastereomeric excesses up to 86%. The starting phosphinates 52a–k were prepared using classical chemistry involving Grignard addition to EtOP(O)Cl2. Phenoxaphosphine Scheme 23 shows the synthesis of one phenoxaphosphine 56 in 55

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• be significantly slower than the desired reduction of the carbonyl function. Practically, the residual 3-chloropropanol remaining from the prior Grignard addition 5→7 step (vide supra) and sec-Bu3B/BEt3 from the reduction were easily separated through washing with Et2O of an (HCl) acidic, aqueous

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• synthesis of the diterpene scopadulcic acid B (79, see Scheme 10), isolated from the Paraguayan plant Scoparia dulcis [66]. Starting from 2-iodobenzaldehyde (65) allyl-Grignard addition took place followed by TBS-protection of the resulting alcohol. The installed double bond was subjected to hydroboration

• vinyl chloride using Vielsmeier’s reagent [163][164]. Dechlorination [165][166] was then achieved and yielded α,β-unsaturated aldehyde 195 upon hydrolysis. Grignard addition to the newly formed aldehyde followed by reoxidation furnished the side chain of compound 196. Treatment of unsaturated ketone 196

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• subunit 2.46 upon elimination of water (Scheme 27, path A). Alternatively, the same intermediate (2.46) can be obtained by an ingenious acid catalysed ring opening of the cyclopropane derivate 2.50, which is readily generated from Grignard-addition to the bis-thiophenyl ketone 2.51 (Scheme 27, path B

A practical synthesis of long-chain iso-fatty acids (iso-C₁₂–C₁₉) and related natural products

• Mark B. Richardson and
• Spencer J. Williams

Beilstein J. Org. Chem. 2013, 9, 1807–1812, doi:10.3762/bjoc.9.210

• -methylpalmitic acid, and 2-oxo-14-methylpentadecane. Keywords: chemoselective reduction; Evans’ auxiliary; Grignard addition; homologation; ionic hydrogenation; Introduction Long-chain iso-fatty acids occur in a broad range of organisms, and are especially abundant in bacteria where, through incorporation into

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• diastereoselectivity around 10:1, with further enhancement following silyl protection and purification. Although the silylated compound 60 proved to be reluctant to form the Weinreb amide, microwave irradiation allowed this process to proceed on a reasonable time scale. Grignard addition to the Weinreb amide afforded

Establishing the concept of aza-[3 + 3] annulations using enones as a key expansion of this unified strategy in alkaloid synthesis

• Aleksey I. Gerasyuto,
• Zhi-Xiong Ma,
• Grant S. Buchanan and
• Richard P. Hsung

Beilstein J. Org. Chem. 2013, 9, 1170–1178, doi:10.3762/bjoc.9.131

• (Scheme 5). Grignard addition to the glutarimide Mg-salt 20 followed by reduction of the Mg salt 21 afforded lactam 22 as an inseparable 1:1 mixture of two diastereomers in 77% overall yield [68][69][70]. Vinylogous amide 23 was prepared by O-methylation of lactam 22 with freshly distilled MeOTf followed

Synthesis and biological evaluation of nojirimycin- and pyrrolidine-based trehalase inhibitors

• Davide Bini,
• Francesca Cardona,
• Matilde Forcella,
• Camilla Parmeggiani,
• Paolo Parenti,
• Francesco Nicotra and
• Laura Cipolla

Beilstein J. Org. Chem. 2012, 8, 514–521, doi:10.3762/bjoc.8.58

• % yield over two steps (Scheme 3). Grignard addition of octylmagnesium bromide to nitrone 30 proceeded cleanly and gave stereoselectively the “all trans” hydroxypyrrolidine 31 as a single adduct in 84% yield, with a stereoselectivity that was in accordance with previously reported Grignard additions on

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• synthesis of (2S,3R,4S)-3,4-dihydroxyproline (30) (Scheme 5). According to their methodology, (R)-2,3-O-isopropylidene-D-glyceraldehyde (24) was treated in a one-pot reaction with benzylamine and then subjected to Grignard addition with vinylmagnesium bromide to provide the alkene 25 as a single

Synthesis of the Benzo- fused Indolizidine Alkaloid Mimics

• Daniel L. Comins and
• Kazuhiro Higuchi

Beilstein J. Org. Chem. 2007, 3, No. 42, doi:10.1186/1860-5397-3-42

• indolizidine alkaloid mimics has been developed. The indolizidine derivatives 8 were prepared via heteroaryl Grignard addition to N-acylpyridinium salts followed by an intramolecular Heck cyclization. Further substitution reactions were developed to demonstrate that heterocycles 8 are good scaffolds for

A divergent asymmetric approach to aza-spiropyran derivative and (1S,8aR)-1-hydroxyindolizidine

• Jian-Feng Zheng,
• Wen Chen,
• Su-Yu Huang,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2007, 3, No. 41, doi:10.1186/1860-5397-3-41

• -hydroxyindolizidine (ent-3). Results The synthesis of aza-spiropyran 7 started from the Grignard addition of malimide 4. Treatment of the THP-protected 4-hydroxybutyl magnesium bromide with malimide 4 at −20°C afforded N,O-acetal 5a as an epimeric mixture in a combined yield of 89%. Subjection of the diastereomeric

• -spiropyran 7 started from the Grignard addition of malimide 4. Treatment of the THP-protected 4-hydroxybutyl magnesium bromide with malimide 4 at −20°C for 2.5 h afforded N,O-acetal 5a as an epimeric mixture in 7:1 ratio and with a combined yield of 89% (Scheme 3). If the reaction was allowed to stir at room

The use of silicon- based tethers for the Pauson- Khand reaction

• Adrian P. Dobbs,
• Ian J. Miller and
• Saša Martinović

Beilstein J. Org. Chem. 2007, 3, No. 21, doi:10.1186/1860-5397-3-21

• give cyclisation precursors in any appreciable yield and not sufficient for use in the Pauson-Khand reaction. The previous method had shown that the Grignard addition to a dichlorosilane had worked well but that the work-up had hydrolysed the remaining silyl chloride bond. Therefore replacing the

• second chlorine atom with a group that could not be hydrolysed would allow the work-up and isolation of the products after the Grignard addition had taken place. Due to the restricted number of chlorodiisopropylsilanes available meant that this group had to be a proton. Therefore it was decided to start