Stereoselective Cyclization using Pd(II)-catalyst via Hemiacetal Intermediates and its Application to Sugar Synthesis

• Project/Area Number: 13640527
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Organic chemistry
• Research Institution: Toyama University
• Principal Investigator: MIYAZAWA Masahiro Toyama University, Faculty of Science, Associate, Professor, 理学部, 助教授 (70209899)
• Project Period (FY): 2001 – 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥3,400,000 (Direct Cost: ¥3,400,000); Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: Palladium catalysy / Hemiacetal / Heterocyclization reaction / Glycosidation / Origo saccharides / Stereoselective / Ribose / DNA / 糖 / スピロケタール

Research Abstract

We recently reported the intramolecular substitution of an allyl alcohol by a heteroatom using a palladium (II) catalyst without activation of the allylic alcohol. We report here highly stereoselective intramolecular cyclization of 6- and 7-formyl allylic alcohols using palladium (II) catalyst in the presence of alcohol via unstable hemiacetal intermediates, in which cyclization occurs without activation of the allylic alcohol in this case too.
1. Stereoselective Cyclization using Pd (II)-catalyst via Hemiacetal Intermediates
Treatment of 7-hydroxy-3-phenyl-5-hexenal with 5 mol% bis(benzonitrile)palladium (II) chloride in THF in the presence of primary, secondary, and tertiary alcohol afforded 6-membered cyclic acetals in 50〜80% yield with highly stereoselectivity. Especially, the relative stereochemistry at C4 and C6 position was 100% cis-selective by treatment with secondary and tertiary alcohols.
2. Total synthesis of D-ribose
A total synthesis of the furanose form of D-ribose, which is component of RNA, is described. The optically active cyclized precursor was prepared from (Z)-2-butene-I,4-diol using asymmetric esterification in 13 steps. Treatment of the precursor with Pd (II) catalyst gave the cyclized product Finally, D-ribose was prepared from the cyclized product in 2 steps.
3. Total synthesis of 2-deoxy-D-ribose
A total synthesis of the furanose form of 2-deoxy-D-ribose, which is component of DNA, is described. Preparation of the cyciized precursor required 8 steps and proceeded in 53% overall yield from (S)-malic acid. Treatment of the precursor with Pd (II) catalyst gave the cyclized product with good stereoselectivity. 2-Deoxy-D-ribose was prepared from the cyclized product in 5 steps.
4. Synthetic studies of Origo saccharides
A disaccharide was obtained under mild conditions through palladium (II) catalyzed coupling reaction of the cyclized precursor and 2-deoxy-D-ribose derivative. The present method should provide a powerful tool in organic synthesis including carbohydrate synthesis.