Synlett 2005(14): 2265-2266  
DOI: 10.1055/s-2005-872265
SPOTLIGHT
© Georg Thieme Verlag Stuttgart · New York

Aluminum Hydride

Krishnarao Lopinti*
Division of Organic Chemistry-III, Indian Institute of Chemical Technology, Hyderabad-500 007, India
Fax: +91(40)27160387; e-Mail: krishna_lopinti@yahoo.co.in;

Further Information

Publication History

Publication Date:
03 August 2005 (online)

Biographical Sketches

Krishnarao Lopinti was born in Srikakulam, Andhra Pradesh in India in 1978. He obtained his B.Sc. (2000) from Acharya Nagarjuna University and M.Sc. (2002) in chemistry from the University of Hyderabad. After qualifying for a CSIR Junior Research Fellowship through a national search examination CSIR-JRF, he began Ph.D. studies under the supervision of Dr P. Radha Krishna at Indian ­Institute of Chemical Technology, Hyderabad, India. His research interests are: synthesis of chiral drug molecules/natural products by using asymmetric synthesis/chiron approach, developing synthetic methodologies, asymmetric Baylis-Hillman reaction and its applications.

Introduction

A diethyl ether solution of three equivalents of lithium aluminum hydride with one equivalent of aluminum chloride generates a mild reducing hydride known as ‘Aluminum Hydride’ (AlH3). [1] This reagent is very useful in synthetic organic chemistry and is easily prepared in situ and used immediately. Lithium aluminum hydride is a powerful reducing agent that can reduce several functional groups. By minimizing its reducing power, selective functional groups can be reduced. In this regard, mixed hydrides have gained a lot of interest in hydride chemistry. Adding a Lewis acid could decrease the reducing power of lithium aluminum ­hydride. AlH3 reduces a wide variety of functional groups. [1] These include aldehydes, ketones, [2] [3] quinines, carboxylic ­acids, anhydrides, acid chlorides, esters, and lactones from which the corresponding alcohol is isolated as product. Similarly, amides, nitriles, oximes and isocyanates are reduced to amines. However, nitro compounds are inert to AlH3. Interestingly sulfides and sulfones are unreactive but disulfides and sulfoxides can be reduced. Tosylates are not reduced.

Abstracts

(A) Reduction of α,β-unsaturated carbonyls and esters: The conversion of α,β unsaturated ketones, aldehydes, and esters into allylic alcohols can be carried out with very good selectivity using AlH3. [4] However, DIBAL is a reagent of choice for this transformation but is costly. [4a] Carboxylic acids and esters are rapidly reduced by AlH3 than LiAlH4 in presence of halides and nitro group. [5]

(B) Reduction of acetals: Cyclic acetals can be reduced to the half protected diols, which has wide applications in carbohydrate chemistry. For instance, acetals (benzylidene derivative) can be ­selectively reduced to a monobenzylated diol. [6]

(C) Reduction of amides: During the reduction of amides to amine, there is a competition between C-O and C-N bond and the cleavage depends upon the reaction conditions. This complication can be avoided with AlH3. A quantitative yield of amine is obtained within a short reaction time. Conjugated amine can be cleanly ­reduced to allylic amines, whereas LiAlH4 reduces also the con­jugated double bond. [7] Reduction of β-lactams to azetidines can be accomplished with AlH3 [8] while ring opening was observed with LiAlH4.

(D) Reduction of nitriles: The less basic AlH3 appears to be better than LiAlH4 for reducing nitriles to amines. [7]

(E) Desulfurisation: Desulfurisation of sultones is rapid and ­proceeds in good yields with AlH3, while LiAlH4 affords poor yields with long reaction times. [9]

(F) Epoxide ring opening: With most epoxides, hydride attack occurs at the least sterically hindered side to give the corresponding alcohol. [10] However due to the electrophilic nature of AlH3 compared to LiAlH4, it is possible for ring opening to occur at the more hindered side. With phenyl substituted epoxides mechanistic studies have shown that attack at benzylic carbenium ion or 1,2-hydride shift followed by hydride attack gives products with the same regiochemistry but with different stereochemistry. [7] [11] The stereoselectivity of AlH3 mediated epoxide ring opening reaction has been studied in depth. [12]

(G) SN2′ allylic rearrangements: Displacement of good leaving group to give the rearranged allylic system can be carried out with AlH3. [13] This reaction appears not to be sterically demanding as a variety of displacements are possible.

(H) Preparation of allenes: Preparation of allenes from propargylic system can also be accomplished. [13] Most systems show a preference for syn elimination. However, mesylates prefer an anti mode of elimination. This same procedure has been used to prepare fluoroallenes. [14]

(I) Miscellaneous: Though alkyl halides are usually inert to AlH3, facile reduction of cyclopropyl halides to cyclopropanes [15] and ­glycosyl fluorides to tetrahydropyrans is known. [16]

    References

  • 1 Finholt AE. Bond AC. Schlesinger HI. J. Am. Chem. Soc.  1947,  69:  1199 
  • 2a Guyon R. Villa P. Bull. Soc. Chim. Fr.  1977,  152 
  • 2b Martinez E. Muchowski JM. Velarde E. J. Org. Chem.  1977,  42:  1087 
  • 3 Corey EJ. Cane D. J. Org. Chem.  1971,  36:  3070 
  • 4a Wilson KE. Seidner RT. Masamune S. J. Chem. Soc., Chem. Commun.  1970,  213 
  • 4b Williams HJ. Tetrahedron Lett.  1975,  1271 
  • 4c Krishna PR. Krishnarao L. Kannan V. Tetrahedron Lett.  2004,  45:  7847 
  • 5 Nung MY. J. Am. Chem. Soc.  1966,  88:  1464 
  • 6 Sakairi N. Tokura S. Kuzuhara H. Carbohydr. Res.  1996,  291:  53 
  • 7a Ashby EC. Sanders JR. Claudy P. Schwarts P. J. Am. Chem. Soc.  1973,  95:  6485 
  • 7b Brown HC. Nung MY. J. Am. Chem. Soc.  1966,  88:  1464 
  • 7c Das BK. Shibata N. Takaeuchi Y. J. Chem. Soc., Perkin Trans. 1  2002,  197 
  • 8 Jackson MB. Mander LN. Spotswood TM. Aust. J. Chem.  1983,  36:  779 
  • 9a Wolinsky J. Marhenke RL. Eustace EJ. J. Org. Chem.  1973,  38:  1428 
  • 9b Smith MB. Wolinsky J. J. Org. Chem.  1981,  46:  101 
  • 10 Maruoka K. Saito S. Ooi T. Yamamaoto H. Synlett  1991,  255 
  • 11 Lansbury PT. Scharf DJ. Pattison VA. J. Org. Chem.  1967,  32:  1748 
  • 12 Elsenbaumer RL. Mosher HS. Morrison JD. Tomaszewski JE. J. Org. Chem.  1981,  46:  4034 
  • 13 Claesson A. Olsson LI. J. Am. Chem. Soc.  1979,  101:  7302 
  • 14 Castelhano A. Krantz A. J. Am. Chem. Soc.  1987,  109:  3491 
  • 15 Muller P. Helv. Chim. Acta  1974,  57:  407 
  • 16 Nicolaou KC. Dolle RE. Chucholowski A. Randal JL. J. Chem. Soc., Chem. Commun.  1984,  1153 

    References

  • 1 Finholt AE. Bond AC. Schlesinger HI. J. Am. Chem. Soc.  1947,  69:  1199 
  • 2a Guyon R. Villa P. Bull. Soc. Chim. Fr.  1977,  152 
  • 2b Martinez E. Muchowski JM. Velarde E. J. Org. Chem.  1977,  42:  1087 
  • 3 Corey EJ. Cane D. J. Org. Chem.  1971,  36:  3070 
  • 4a Wilson KE. Seidner RT. Masamune S. J. Chem. Soc., Chem. Commun.  1970,  213 
  • 4b Williams HJ. Tetrahedron Lett.  1975,  1271 
  • 4c Krishna PR. Krishnarao L. Kannan V. Tetrahedron Lett.  2004,  45:  7847 
  • 5 Nung MY. J. Am. Chem. Soc.  1966,  88:  1464 
  • 6 Sakairi N. Tokura S. Kuzuhara H. Carbohydr. Res.  1996,  291:  53 
  • 7a Ashby EC. Sanders JR. Claudy P. Schwarts P. J. Am. Chem. Soc.  1973,  95:  6485 
  • 7b Brown HC. Nung MY. J. Am. Chem. Soc.  1966,  88:  1464 
  • 7c Das BK. Shibata N. Takaeuchi Y. J. Chem. Soc., Perkin Trans. 1  2002,  197 
  • 8 Jackson MB. Mander LN. Spotswood TM. Aust. J. Chem.  1983,  36:  779 
  • 9a Wolinsky J. Marhenke RL. Eustace EJ. J. Org. Chem.  1973,  38:  1428 
  • 9b Smith MB. Wolinsky J. J. Org. Chem.  1981,  46:  101 
  • 10 Maruoka K. Saito S. Ooi T. Yamamaoto H. Synlett  1991,  255 
  • 11 Lansbury PT. Scharf DJ. Pattison VA. J. Org. Chem.  1967,  32:  1748 
  • 12 Elsenbaumer RL. Mosher HS. Morrison JD. Tomaszewski JE. J. Org. Chem.  1981,  46:  4034 
  • 13 Claesson A. Olsson LI. J. Am. Chem. Soc.  1979,  101:  7302 
  • 14 Castelhano A. Krantz A. J. Am. Chem. Soc.  1987,  109:  3491 
  • 15 Muller P. Helv. Chim. Acta  1974,  57:  407 
  • 16 Nicolaou KC. Dolle RE. Chucholowski A. Randal JL. J. Chem. Soc., Chem. Commun.  1984,  1153