Complex metal hydrides and selectrides

The complex metal hydrides are generally salts in which the anions contain hydrides
They typically contain more than one type of metal or metalloid and can be soluble or react with water
General Formula of Complex Metal Hydrides- MxM'yHn
where, M= Alkali metal; M'= Metal/Metalloid

1. Complex Metal Hydrides and Selectrides -Minhaj Sohail Shakil Patel (MC/2019/15) 1

2. Introduction General Formula of Complex Metal Hydrides- M x M' y H n where, M = Alkali metal; M' = Metal/Metalloid The complex metal hydrides are generally salts in which the anions contain hydrides They typically contain more than one type of metal or metalloid and can be soluble or react with water Well known examples consists of group 13 elements especially NaAlH 4 , LiAlH 4 , LiBH 4 The complex metal hydrides are soluble in ethereal solvents like Diethylether , Tetrahydrofuran (THF), Dimethoxyethane (DME) All the complex metal hydrides act as sources of nucleophilic hydride and therefore are more reactive towards electrophilic species. 2

3. Classification of Complex Metal Hydride Complex Metal Hydrides General Complex Metal Hydrides Eg. LiAlH 4 LiBH 4 NaBH 4 Zn(BH 4 ) 2 NaCNBH 4 LiAlH(OEt) 3 Selectrides L- Selectride K- Selectride N- Selectride 3

4. Hydride based reducing reagents M ( Al H 4 ) M ( B H 4 ) Li ( Al H 4 ) Li ( B H 4 ) Na B H 3 CN Na ( B H 4 ) Na B H ( OAc ) 3 Zn ( B H 4 ) 2 Na B H 4 ,CeCl 3 4

5. Reduction by Hydride Transfer LiAlH 4 is a strong reducing agent while NaBH 4 is mild reducing agent. NaBH 4 is chemoselective and it is used when water and alcohol are used as solvents while LiAlH 4 is used with ethereal solvents. 5

6. Mechanism of Hydride Transfer The Hydrogen nucleus can migrate from one atom to another accompanied by zero, one or two electrons and the process is termed as proton transfer, hydrogen transfer or hydride transfer respectively General mechanism of hydride transfer is as follows: 6

7. Selectrides Selectrides are the reducing reagents which produces geometrically pure compounds Selectrides are the derivatives of Borohydrides which are bulky as they are highly substituted with alkyl groups Steric hinderance α Stereoselectivity The bulky nature of the selectrides is responsible for high stereoselectivity of the compounds Selectrides are of 3 types- L- selectride (Lithium tri-sec-butyl borohydride) K- selectride (Potassium tri-sec-butyl borohydride) N- selectride (Sodium tri-sec-butyl borohydride) 7

8. Structure and General Reaction of Selectrides Structure: L- selectride N- selectride K- selectride General reaction: 8

9. Stereoselectivity of Selectrides The stereoselectivity of the slectrides is strongly influenced by the steric and solvent factors In the α , β unsaturated cyclic ketone, the selectrides show 1,4-reduction Example 9

10. Stereochemical aspects When there is substitution at the β position of α , β unsaturated cyclic ketones then instead of 1,4- reduction there will be 1,2-reduction Example- But when there is substitution at the α position then 1,4- reduction occurs 10

11. Stereochemical Aspects Since the selectrides are bulkier reducing agents ,the attack of the slectride will be from less hindered site In the example given below the L- selectride will attack from the equatorial position because of the 1,3 diaxial interaction giving axial alcohol 11

12. Stereochemical Aspects In the bicyclic compounds the favorable product is in endo form with –OH group in the axial position In the case of camphor, the most favorable reduction product is in exo form with –OH group on the equatorial position 12

13. L- selectride In the example given below, L- selectride is used in the synthesis of Benzomorphan derivatives 13

14. K- selectride Another example is the reduction of Cyclohexanone derivatives with NaBH 4 gives 74% trans-4-OH PZQ while reduction with K- selectride gives 99.5% geometrically pure racemic cis-4-OH PZQ 14

15. N- selectride Chelation control enforces a syn-periplanar relationship between the amine and ketone groups and leads to the anti-diastereomer, whereas Felkin -Anh control, which utilizes a dihedral angle of about 90° between the amine and ketone groups to minimize stereo-electronic interactions, leads to the syn-diastereomer 15

16. References https://en.wikipedia.org/wiki/Complex_metal_hydride https://en.chem-station.com/reactions-2/2017/05/lnk-selectride.html Hoffman RV, Maslouh N. A Highly Stereoselective Synthesis of Carbamate Protected anti-1, 2-Aminoalcohols. Comins DL, Zhang YM, Joseph SP. Enantiopure N- acyldihydropyridones as synthetic intermediates: Asymmetric synthesis of benzomorphans. Organic Letters. 1999 Aug 26;1(4):657-60. Kiec‐Kononowicz K, Farghaly ZS, Blaschke G. Synthesis and Properties of cis‐and trans‐4‐Hydroxypraziquantel. Archiv der Pharmazie . 1991;324(4):235-7. 16

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