Sodium Bis(methoxyethoxy)aluminium Hydride

Introduction

Sodium bis(methoxyethoxy)aluminium hydride (Red-Al^®) is a versatile reducing agent which was developed by Vit and co-workers in 1968. [¹]

Figure 1

Red-Al^® exhibits similar reactivity to lithium aluminium hydride but is significantly less sensitive towards air and has higher solubility in aromatic solvents and ethers. In addition, the reactions can be performed at temperatures of up to 200 ˚C. [²] The general mechanism of reduction using Red-Al^® involves an initial reaction with an alcohol, formation of hydrogen, and subsequent hydride transfer in an intramolecular fashion. In the absence of such a moiety, the hydride reduction via a mechanism akin to lithium aluminium hydride can be envisaged. The reagent has been used towards the synthesis of many natural products. [³] Some less conventional uses involve the cleavage of benzyl ethers of vicinal methoxy-containing compounds. [4]

References

• 1 Vit J. Čésenský B. Macháček J. FR 1515582 19680301, 1968, 
• 2 Seyden-Penne J. Reductions by the Alumino- and Borohydrides in Organic Synthesis   Wiley-VCH; New York: 1997. 2nd ed
• 3a Ishizaki M. Hoshino O. Iitaka Y. J. Org. Chem.  1992,  57:  7285 
• 3b Nicolaou KC. Pihko PM. Bernal F. Frederick MO. Qian W. Uesaka N. Diedrichs N. Hinrichs J. Koftis TV. Loizidou E. Petrovic G. Rodriquez M. Sarlah D. Zou N. J. Am. Chem. Soc.  2006,  128:  2244 
• 3c Myers AG. Siu M. Ren F. J. Am. Chem. Soc.  2002,  124:  4230 
• 3d Choi Y. Ishikawa H. Velcicky J. Elliott GI. Miller MM. Boger DL. Org. Lett.  2005,  7:  4539 
• 4 Kametani T. Huang S.-P. Ihara M. Fukumoto K. J. Org. Chem.  1976,  41:  2545 
• 5 Koide K. Meta CT. Org. Lett.  2004,  6:  1785 
• 6 Igawa K. Tomooka K. Angew. Chem. Int. Ed.  2006,  45:  232 
• 7 Nemoto T. Ohshima T. Shibasaki M. J. Am. Chem. Soc.  2001,  123:  9474 
• 8 Cao H. van Ornum SG. Deschamps J. Flippen-Anderson J. Laib F. Cook JM. J. Am. Chem. Soc.  2005,  127:  933 
• 9 Ghosh AK. Gong G. J. Org. Chem.  2006,  71:  1085 
• 10 Semmelhack MF. Stauffer RD. Yamashita A. J. Org. Chem.  1977,  42:  3180 
• 11 Voight EA. Bodenstein MS. Ikemoto N. Kress MH. Tetrahedron Lett.  2006,  47:  1717 
• 12 Ma P. Martin VS. Masamune S. Sharpless KB. Viti SM. J. Org. Chem.  1982,  47:  1378 
• 13 Yamazaki T. Ichige T. Kitazume T. Org. Lett.  2004,  6:  4073 
• 14 Corey EJ. Smith JG. J. Am. Chem. Soc.  1979,  101:  1038 
• 15 Cid JM. Alonso JM. Andrés JI. Fernández J. Gil P. Iturrino L. Matesanz E. Meert TF. Megens A. Sipido VK. Trabanco AA. Bioorg. Med. Chem. Lett.  2004,  14:  2765 
• 16 Sih CJ. Heather JB. Peruzotti GP. Price P. Sood R. Lee LFH. J. Am. Chem. Soc.  1982,  104:  1109