Lewis Acid‐Mediated Addition of Amino Acid‐Substituted α‐Allylsilanes to Aromatic Acetals |
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| Authors: | Michael A Brook Mustafa Mohamed |
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| Institution: | 1. Department of Chemistry, McMaster University, 1280 Main St. W., Hamilton, Ontario, Canada, L8S 4?M1, (fax: +1?905?522?2509)It is a pleasure to celebrate the 75th birthday of Prof. Dieter Seebach. In addition to his prodigious contributions to the art of synthetic organic chemistry, Seebach is known for his ability to assimilate enormous amounts of literature and to codify the trends therein for the rest of us. A teacher leaves his legacy through his students and his writings, and, on that basis, Seebach has an enormously strong legacy. Prof. Seebach taught me many things about being a scientist, most important among them was to always put one's current work in the context of the field, to look for trends, and to follow up exceptions to the rule. I am grateful to have been a small part of the team: it had a profound and positive effect on my scientific career.;2. Department of Chemistry, McMaster University, 1280 Main St. W., Hamilton, Ontario, Canada, L8S 4?M1, (fax: +1?905?522?2509);3. Current address: Dr. Mustafa Mohamed, Senior Chemist, Electronics, Dow Corning Corporation, Auburn, MI 48686‐0994, USA (phone: +1?989?496?7024;4. fax: +1?989?496?7084). |
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| Abstract: | Unnatural amino acids extend the pharmacological formulator's toolkit. Strategies to prepare unnatural amino acid derivatives using Lewis acid‐activated allylsilane reactions are few. In this regard, we examined the utility of allylsilanes bearing an amino acid substituent in the reaction. Diastereoselective addition of methyl 2‐(N‐PG‐amino)‐3‐(trimethylsilyl)pent‐4‐enoate and methyl (E)‐2‐(N‐PG‐amino)‐3‐(trimethylsilyl)hex‐4‐enoate (PG=protecting group), 2 and 13 , respectively, to aromatic acetals in the presence of Lewis acids is described. Of those examined, TiCl4 was found to be the most effective Lewis acid for promoting the addition. At least 1 equiv. of TiCl4 was required to achieve high yields, whereas 2 equiv. of BF3?OEt2 were required for comparable outcomes. Excellent selectivity (>99% syn/anti) and high yield (up to 89%) were obtained with halo‐substituted aromatic acetals, while more electron‐rich electrophiles led to both lower yields and diastereoselectivities. |
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| Keywords: | Amino acids Lewis acids Allylation Silanes allyl‐ Catalysis |
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