Lithium Aminoborohydrides: Reagents with Multiple Personalities

Chapter 2

Lithium Aminoborohydrides: Reagents with Multiple Personalities

Downloaded by NANYANG TECHNOLOGICAL UNIV on June 8, 2016 | http://pubs.acs.org Publication Date: February 26, 2001 | doi: 10.1021/bk-2001-0783.ch002

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Christian T. Goralski , Bakthan Singaram , Christopher J. Collins , Jennifer R. Cuzens , and Marc Lanz 2

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Contract Manufacturing Services, The Dow Chemical Company, 1710 Building, Midland,MI48674 Department of Chemistry and Biochemistry, University of California at Santa Cruz, Santa Cruz,CA95064 2

This chapter describes newly discovered reactions and synthetic utilities of lithium aminoborohydrides (LABs) including: (1) the reduction of nitriles to amines, (2) the direct synthesis of amine-borane complexes from L A B s and benzylic or alkyl halides (nitrogen transfer), and (3) the "tandem nitrogen transfer/reduction" of halogen-substituted benzonitriles to give the corresponding aminobenzylamines.

Introduction In 1984, Hutchins and coworkers ( i ) reported the preparation (Figure 1) and reducing properties of sodium aminoborohydrides. These reagents were NaH H B:HN(CH )

2

H B:H NC(CH )

3

3

3

3

2

3

THF NaH THF

NaH BN(CH ) 3

3

2

NaH BNHC(CH ) 3

3

3

Figure I. Preparation ofsodium aminoborohydrides.

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© 2001 American Chemical Society Ramachandran and Brown; Organoboranes for Syntheses ACS Symposium Series; American Chemical Society: Washington, DC, 2001.

19 reported to reduce aldehydes and ketones to alcohols, esters to alcohols, and primary amides to amines in good to excellent yields. Several anomalous reactions were also reported with sodium dimethylaminoborohydride in which the dimethylamine portion of the reagent was transferred to give the corresponding tertiary amine from an alkyl iodide and the corresponding amino alcohol from an epoxide (Figure 2).

NaH BN(CHj) (2 eq)


3

2

THF, 25 °C, 26 h

^0

N(CH )

2

,N(CH )

2

3

79% Isolated yield

NaH BN(CH ) (leq) 3

3

2

3

THF, 25 °C, 70 h 87% Isolated yield

Figure 2. Reaction of sodium aminoborohydrides with alkyl iodides and expoxides. Several years ago, we reported the synthesis and synthetic utility of lithium aminoborohydrides (LABs): a new class of powerful, safe, and highly selective reducing agents (2, 3). These reagents performed many of the transformations for which lithium aluminum hydride is usually used. Thus, the following reduction reactions were carried out with L A B s : aldehydes and ketones to alcohols, esters to alcohols, α,β-unsaturated ketones to allylic alcohols, α,β-unsaturated esters to allylic alcohols, alkyl halides to hydro carbons, azides to amines, and epoxides to alcohols. These reduction reactions are summarized in Figure 3. We had not, until recently, however, observed any of the nitrogen transfer reactions with L A B s reported earlier by Hutchins. This summary will describe recently observed reactions of L A B s , which display their multiple personalities (properties) and utility in synthetic organic chemistry.

Recently Reported Reduction Reactions Before embarking on a discussion of new reactions, it will be useful to describe recently reported examples of the synthetic utility of the reducing capabilities of the L A B s . Myers has recently described a practical synthesis of chiral alcohols employing pseudoephedrine as a chiral auxiliary (4). A n amide of pseudoephedrine is first deprotonated with L D A and then alkylated with the appropriate alkyl halide to give the substituted amide with 97-99% de. The amide is then reduced to the alcohol with lithium pyrrolidinoborohydride to give

Ramachandran and Brown; Organoboranes for Syntheses ACS Symposium Series; American Chemical Society: Washington, DC, 2001.

20 the desired chiral alcohol in high chemical yield and greater than 97-99% ee (Figure 4, Table I).


OH (R\ R*= Alkyl, aryl) 1 h, 0 °C, In air, 95% yield OH

ÏÏ

OH • F (R ,R = alkyl, aryl) 100% 1,2-IH] 1 h, 0 °C, in air, 95% yield 1

(R , R =H, alkyl, aryl) 100% 1,2-[H] 1 h, 0 °C, in air, 95% yield 1

2

2

R-CH (R= Alkyl, aryl)

R ' "NRa 1

3

99% yield

Figure 3. Summary of the reduction reactions of lithium aminoborohydrides. (Reproducedfrom reference 2. Copyright 1994 American Chemical Society.)

Figure 4. Reductive cleavage of pseudoephedrine amides with lithium pyrrolidinoborohydride. In the last entry of Table I, it is noted that the reduction had to be done with lithium aminoborohydride ( L i H B N H ) . Myers further expanded the utility of this reagent with additional examples of the reduction of alkylated pseudoephedrine amides to chiral alcohols of high ee (Table II), and the reduction of AyV-disubstituted dodecanecarboxamides and 1-adamantanecarboxamides to the corresponding alcohols, respectively (Table III) (5). 3

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Table I. Reduction of Pseudoephedrine Amides with Lithium Pyrrolidinoborohydride

Alcohol

Alkylated Amide

R CH

3

CH C H

CH

3

(CH ) CH,

CH C H 2

6

2

2

CH C$H 2

2

3

CH 6

5

3

3

(CH ),CH, 2

5

(CH ) CH

6

CH

5

CH QH

3

2

CH CH

Û

2

5

Yield, %

ee, %

Yield, %

>99

90

99

84

>99

80

99

81

97

95

97

87

98

90

98

88

>99

87

99

88

>99

92

88

80

de, %

R'

5

3

e

Reduction with LiH BNH 3

2

SOURCE: Reproducedfromreference 4. Copyright 1994 American Chemical Society.


Ramachandran and Brown; Organoboranes for Syntheses ACS Symposium Series; American Chemical Society: Washington, DC, 2001. CH, CH,

CHjOCHjC*!!,

îï95

Time, fc

SOURCE: Reproduced with permissionfromreference 5. Copyright 1996 Ekcvicr Sctercc Ltd

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23

Temp, X

Reactions run wtlb LiHjBNHj (4.0-4.5 cqurv) generated m situ i l 0 °C.

OH

CH,

Ο

£11,

OH

C H , CH^CH,

OH

^9

tic, %

2

- X'

}

t

T;n QC\{ c n.

Table U . Reduction of Pseudoephedrine Amides with Lithium Aminoborohydride

Veil, %


ec, %

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Table III. Reduction of Amides with Lithium Aminoborohydride

Amide CH (CH ) CONEt


3

2

l0

ÇONEt

2

Temp, °C

Time, h

Isol. Yield Alcohol, %

Isol. Yield Amine, %

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1.3

94

Lithium Aminoborohydrides: Reagents with Multiple Personalities

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