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All 16 posts Subject: Enhancing NaBH4 Reactivity & Selectivity Please login to post Down

Rhodium
(Chief Bee)
09-20-03 18:37
No 460118
User Picture       Enhancing NaBH4 Reactivity & Selectivity
(Rated as: excellent)

Methods of enhancement of reactivity and selectivity of sodium borohydride for applications in organic synthesis
Mariappan Periasamy and Muniappan Thirumalaikumar
Journal of Organometallic Chemistry, Vol 609, No 1-2, pp. 137-151 (2000) (https://www.rhodium.ws/pdf/enhancing.nabh4.reactivity.and.selectivity.pdf)
DOI:10.1016/S0022-328X(00)00210-2

Abstract

NaBH₄ does not reduce carboxylic acids, esters, amides and nitriles under ambient conditions. However, the reactivity of NaBH₄ can be enhanced by the addition of certain additives. For example, addition of iodine to NaBH₄ in THF provides BH₃.THF that is useful for hydroborations and reductions of various functional groups. The aldehydes and ketones are reduced in a fast manner by the NaBH₄ reagent. Even so, the selectivities realised in such reductions can be enhanced using NaBH₄ along with another additive. In this article, various methods used for the enhancement of reactivity and selectivity of NaBH₄ in organic synthesis are described.

Article Outline

1. Introduction
2. Hydroboration of alkenes and alkynes
3. Reduction of carboxylic acids
4. Reduction of amino acids and their derivatives
5. Reduction of carboxylic acid esters
6. Reduction of carboxylic acid amides
7. Reduction of nitriles
8. Reduction of acid chlorides
9. Reduction of nitro compounds
10. Reduction of aldehydes and ketones
10.1. Reduction of ketones using NaBH₄ supported reagents
10.2. Reduction of aldehydes and ketones under phase transfer catalysis
10.3. Asymmetric reduction of ketones using NaBH₄ and a chiral auxiliary
10.4. Reductive amination of aldehydes and ketones
10.5. Reduction of epoxy ketones
11. Miscellaneous
11.1. Reduction of carbinols and benzylic alcohols
11.2. Reduction of azides
11.3. Reduction of oximes and oxime ethers
11.4. Reduction of C=N and N=N functional groups
11.5. Reduction of alkyl and aryl halides
11.6. Cleavage of ethers using NaBH₄ and additives
11.7. Deoxygenation of phenols and enols using NaBH₄ and additives
11.8. Reduction of sulfides using NaBH₄ and additives
11.9. Reactions using Bu₃SnCl–AIBN in combination with NaBH₄
12. Conclusions

Rhodium
(Chief Bee)
09-30-03 00:45
No 461734
User Picture       Reducing carboxylic acids & esters with NaBH4
(Rated as: excellent)

Reductions of Carboxylic Acids and Esters with NaBH₄ in Diglyme at 162°C
Hua-Jie Zhu and Charles U. Pittman Jr.
Synth. Commun. 33(10), 1733–1750 (2003) (https://www.rhodium.ws/pdf/borohydride.refluxing.diglyme.pdf)
DOI:10.1081/SCC-120018935

Abstract

Aromatic esters, including the extremely sterically hindered ester: tert-amyl 2-chlorobenzoate, are readily reduced to the corresponding benzyl alcohols in high yield with NaBH₄ in refluxing diglyme (162°C). In sharp contrast, aliphatic esters usually gave only low yields of alcohols. Instead, diglyme fragmentation products are formed which undergo transesterification reactions, producing complex product mixtures including products such as RCOOCH₂CH₂OCH₃. The mechanism of this process involves sodium borohydride-induced S_N2 cleavage of diglyme (hydride attack) at high temperatures. However, when the extremely electron rich 3,4,5-trimethoxybenzoic acid is treated with NaBH₄/diglyme at 162°C (with or without an equivalent of LiCl), no 3,4,5-trimethyoxybenzyl alcohol is formed. The electron rich and hindered ester, tert-amyl-3,4,5-trimethoxybenzoate, also does not reduce under these conditions (with or without LiCl). However, both methyl and isopropyl 3,4,5-trimethoxybenzoate esters were converted into 3,4,5-trimethoxybenzyl alcohol in good yields in NaBH₄/diglyme/LiCl at 162°C. These reductions did not occur unless LiCl was present, illustrating the electron releasing effect of the three methoxy functions which reduce the carbonyl group’s reactivity.

A New Powerful Reducing Agent - Sodium Borohydride in the Presence of Aluminum Chloride and Other Polyvalent Metal Halides
Herbert C. Brown, B. C. Subba Rao
J. Am. Chem. Soc. 78(11), 2582-2588 (1956) (https://www.rhodium.ws/pdf/borohydride-alcl3.pdf)

Abstract

The addition of aluminum chloride to sodium borohydride in the dimethyl ether of diethylene glycol (diglyme) gives a clear solution with enormously more powerful reducing properties than those of sodium borohydride itself. Esters, lactones and carboxylic acids are readily reduced to the corresponding alcohols. Sodium salts of the carboxylic acids are not reduced, so that the reagent permits the selective reduction of an ester group in the presence of the carboxylate group. Nitro groups are not attacked by the reagent, permitting the ready reduction of nitro esters to the corresponding nitro alcohols. Nitriles are reduced to primary amines in good yield.

Rhodium
(Chief Bee)
10-01-03 19:28
No 462116
User Picture       NaBH4 Deoxygenation of Benzyl Ketones/Alcohols
(Rated as: excellent)

Reduction of Monobenzylic Alcohols With Sodium Borohydride/Trifluoroacetic Acid
CF Nutaitis, JE Bernardo.
Synth Commun 20, 487 (1990) (https://www.rhodium.ws/djvu/nutaitis.djvu) (retrieved by lugh)

Hydrogenation of Diaryl and Arylalkyl Ketones by Sodium Borohydride and Aluminum Chloride
A Ono, T Maruyama, N Suzuki.
Synth Commun 17, 1001 (1987) (https://www.rhodium.ws/djvu/ono.djvu) (retrieved by lugh)

Rhodium
(Chief Bee)
11-23-03 17:10
No 472667
User Picture       Selective Reductions using Al and Boron Hydrides
(Rated as: excellent)

Selective reduction of organic compounds with aluminum and boron hydrides
Nung Min Yoon
Pure & Appl. Chem., 68(4), 843-848 (1996) (https://www.rhodium.ws/djvu/selective.hydride.reductions.djvu)

Abstract
Several new selective reductions of organic compounds using complex metal hydrides and hydride reducing systems are discussed. Sodium diethylpiperidinoaluminate is an excellent agent for the partial reduction of esters to the corresponding aldehydes. Borohydride exchange resin (BER) is a convenient reagent for the chemoselective reduction of carbonyl compounds and also for reductive amination. BER-Ni₂B has proved to be an excellent chemoselective reducing agent for olefins, halides, azides, and nitro compounds in the presence of many functional groups such as epoxides, esters, amides, and nitriles. On the other hand, BER-Cu is a reagent of choice for the reduction of ,-unsaturated acid derivatives and amine N-oxides.

Rhodium
(Chief Bee)
11-27-03 09:31
No 473449
User Picture       NaBH4/BiCl3/THF: Reduction of Nitro & Imine
(Rated as: excellent)

Bismuth(III)Chloride - Sodium Borohydride:
A New and Efficient System for the Selective Reduction of Nitro and Imine Functionalities
Harsha N. Borah, Dipak Prajapati and Jagir S. Sandhu
J. Chem. Research (S), 228-229 (1994) (https://www.rhodium.ws/pdf/nitro2amine.nabh4-bicl3.pdf)

A novel reduction system prepared from bismuth trichloride and sodium borohydride reduces aromatic nitro compounds and azomethines to the corresponding amines in 65-90% yields.

Nitro-aliphatic compounds which have been traditionally reduced by high-pressure hydrogenation, lithium aluminium hydride or aluminium amalgam, when treated with the bismuth trichloride-sodium borohydride reagent system in tetrahydrofuran at 60°C, give the corresponding amines in 60-65% yields. This reagent system is used successfully for the selective reduction of the carbon-nitrogen double bond of conjugated imines, keeping the carbon-carbon double bond intact, to the corresponding secondary amines (4a-c) in excellent yields.

In conclusion, the present new method employing bismuth trichloride as a promoter of NaBH₄-catalysed reduction, is more efficient, highly selective, involves simple work-up and affords products in high yields. Moreover, bismuth trichloride is inexpensive and easy to handle. As far as mechanism is concerned it is difficult to postulate any at this stage, but certainly neither acidic nor basic conditions prevailed during the reaction, as groups sensitive to these conditions remained intact.

Reaction of Aromatic and Aliphatic Nitro Compounds with Bismuth Trichloride and Sodium Borohydride

Typical Procedure

Bismuth trichloride (0.630 g, 2 mmol) was suspended in tetrahydrofuran (THF) (25 ml) and sodium borohydride (0.076 g 2 mmol) was added with stirring at room temperature. To this solution was added p-chloronitrobenzene (0.314 g, 2 mmol) and the remaining sodium borohydride (0.076 g, 2 mmol) w added in portions gradually at 60 °C; the reaction mixture was then stirred for 1-2 h at 60°C (see Table 1). After cooling, the solvent was removed under reduced pressure and water (30 ml) was added. The residue was extracted with diethyl ether (3x30 ml), dried over anhydrous sodium sulfate and distilled. The p-chloroaniline thus obtained was purified by column chromatography using ethyl acetate-light petroleum (bp 60-80°C) (1:6) as the eluent, mp 69-70°C, yield 90%. Other amines were prepared similarly and their characteristics are recorded in Table 1. The same products could also be obtained, but less effectively, under similar conditions using ethanol instead of THF as a solvent.

Rhodium
(Chief Bee)
05-07-04 01:37
No 505481
User Picture       Nitrobenzene to Aniline with NaBH4/NiCl2
(Rated as: excellent)

Reduction with Sodium Borohydride-Transition Metal Salt Systems. I.¹
Reduction of Aromatic Nitro Compounds with the Sodium Borohydride-Nickelous Chloride System
Atsuko Nose and Tadahiro Kudo
Chem. Pharm. Bull. 29(4), 1159-1161 (1981) (https://www.rhodium.ws/pdf/nitrobenzene2aniline.nabh4-nicl2.pdf)

Summary
The reduction of aromatic nitro compounds with the sodium borohydride-nickelous chloride system was examined. Aromatic nitro compounds afforded primary amines in high yield without by-products. Similarly, nitroso-, azoxy-, azo- and hydroxylaminobenzene were reduced with sodium borohydride-nickelous chloride to give aniline.

In recent years, significant advances have been made in the reduction of a variety of functional groups with sodium borohydride.² However, in general, sodium borohydride hardly reduces aromatic nitro compounds under ordinary conditions. In the previous paper,³ it was reported that aromatic nitro compounds afforded the corresponding azoxy, azo and primary amine derivatives on heating directly with sodium borohydride.

Interestingly, it has recently been reported that aromatic nitro compounds can be reduced with sodium borohydride-transition metal salt systems, such as NaBH₄-CoCl₂,^4a,b NaBH₄-Co(pyridyl)₂⁵ and NaBH₄-palladized charcoal.⁶ In the present work, we investigated the sodium borohydride-nickelous chloride system in order to improve the yield in the reduction of aromatic nitro compounds with sodium borohydride-transition metal salt systems.

The reaction of aromatic nitro compounds with sodium borohydride-nickelous chloride hexahydrate at room temperature gave the corresponding primary amines in good yields. As shown in Table I, irrespective of the existence of an electron-donating or electron-withdrawing substituent, these reduction proceeded to give the corresponding primary amines without byproducts. It appears that the sodium borohydride-nickelous chloride system is superior to the cobaltous chloride-sodium borohydride system^4a for the reduction of aromatic nitro compounds.

According to the method described above, nitrosobenzene (21), azoxybenzene (22), azobenzene (23) and phenylhydroxylamine (24) were reduced to aniline. It was reported that azoxybenzene and azobenzene were reduced to hydrazobenzene with sodium borohydride-cobaltous chloride hexahydrate.⁷ Thus, it appears that the reducing power of the sodium borohydride-nickelous chloride system is greater than that of the sodium borohydride-cobaltous chloride system.

It can be presumed that the sodium borohydride-nickelous chloride system provides an useful and simple synthetic route under mild conditions for the preparation of aromatic primary amines from nitro compounds.

Experimental

Commercially available nickelous chloride hexahydrate and sodium borohydride were used throughout this work.

The procedures for the reduction of 2 and 7 with sodium borohydride-nickelous chloride system will be described in detail as typical examples. The other aromatic nitro compounds, 21, 22, 23 and 24 were reduced similarly, and the reaction conditions are listed in Tables I and II. All spectral data of products were identical with those of the corresponding authentic samples.

Reduction of 2

Compound 2 (1.10 g, 8 mmol) and nickelous chloride hexahydrate (3.80 g, 16 mmol) were dissolved in 99% methanol (30 ml) and sodium borohydride (1.21 g, 32 mmol) was added in portions with stirring under cooling for 30 minutes, then the stirring was continued for 30 minutes at room temperature (20°C). After the removal of methanol by distillation, the black precipitate was dissolved in 10% hydrochloric acid (7, 8 and 9 were dissolved in conc. hydrochloric acid), then the acidic solution was basified by the addition of conc. ammonium hydroxide and extracted with ethyl acetate and the solution was dried over magnesium sulfate. After evaporating off the ethyl acetate, the residue was distilled under reduced pressure to give 813 mg (95.0%) of 12, bp 103-104°C (30 mmHg) (lit.⁸ bp 200.35°C), mp 44-45°C (lit.⁸ mp 43.5°C). All spectral data of 12 were identical with those of an authentic sample.

Reduction of 7

Compound 7 (873 mg, 8 mmol) and nickelous chloride hexahydrate (3.80 g, 16 mmol) were dissolved in 99% methanol (30 ml) and sodium borohydride (1.21 g, 32 mmol) was added in portions with stirring under cooling for 30 minutes, then the stirring was continued for 30 minutes at room temperature (20°C). After usual work-up as described above, the residue was crystallized from water to give 770 mg (88.2%) of 17, colorless plates, mp 188-190°C (lit.⁹) mp 189-190°C). This was identical with an authentic sample on the basis of mixed mp determination, and comparison of IR and UV spectra.

References and Notes

[1] This work was presented at the 99th Annual Meeting of the Pharmaceutical Society of Japan, Aug. 1979, Sapporo, Abstract 30E 2-5.
[2] S. Yamada, Yuki Gosei Kagaku Kyokai Shi, 28, 1083 (1970)
[3] A. Nose and T. Kudo, Yakugaku Zasshi, 97, 116 (1977)
[4] a) T. Satoh and S. Suzuki, Tetrahedron Lett., 4555 (1969); b) T. Satoh and S. Suzuki, Chem. Ind. (London), 1626 (1970)
[5] A.A. Vlcek and A. Rusina, Proc. Chem. Soc. (London), 161 (1961)
[6] T. Neilson, H.C.S. Wood, and A.G. Wylie, J. Chem. Soc., 371 (1962)
[7] A. Kasahara and T. Motomiya, Nippon Kagaku Zasshi, 86, 1343 (1965)
[8] J.F.T. Berliner and O.E. May, J. Am. Chem. Soc., 49, 1008 (1927)
[9] S.A. Dunn, J. Am. Chem. Soc., 76, 6191 (1954)

^{The Hive - Clandestine Chemists Without Borders}

Rhodium
(Chief Bee)
05-16-04 17:56
No 507524
User Picture       Reduction of Nitrile/Nitro/Amide to Primary Amines
(Rated as: good read)

_{Reduction of Organic Compounds With Sodium Borohydride-Transition Metal Salt Systems (1)}
Reduction of Organic Nitriles Nitro and Amide Compounds to Primary Amines
Toshio Satoh, Shuichi Suzuki, Yoshio Suzuki, Yutaro Miyaji and Zenjiro Imai
Tetrahedron Letters 4555-4558 (1969) (https://www.rhodium.ws/pdf/nabh4.metal.salts.pdf)

^{The Hive - Clandestine Chemists Without Borders}

Rhodium
(Chief Bee)
09-12-04 21:09
No 531058
User Picture       Sodium Borohydride-Cobaltous Chloride Reduction
(Rated as: good read)

Mechanism of sodium borohydride-cobaltous chloride reductions
Stephen W. Heinzman, Bruce Ganem
J. Am. Chem. Soc. 104, 6801-6802 (1982) (https://www.rhodium.ws/pdf/nabh4-cobaltous.chloride.pdf)

_{Mentioned before in Post 122820 (dormouse: "Reductions with metal borohydrides -Strontium", Serious Chemistry)}

^{The Hive - Clandestine Chemists Without Borders}

java
(Hive Addict)
09-13-04 02:55
No 531096
User Picture       Hydrogenolysis of Diaryl and Aryl alkyl Ketones...
(Rated as: good read)

Note:_{this was posted over at Post 523004 (java: "Hydrogenolysis of Phenylalaninol.....", Serious Chemistry) but thought it might be a good addition to this thread.....}

Hydrogenolysis of Diaryl and Aryl Alkyl Ketones and Carbinols by Sodium Borohydride and Anhydrous Aluminum(III) Chloride

AoiOno, Nobuko Suzuki, Junko Kamimura
Synthesis 736, 1978

Abstract Diaryl ketones such as benzophenone and fluorenone, aryl alkyl ketones such as acetophenone, 4-chloroacetophenone and 4-methylacetophenone, and arylcarbinols such as benzhydrol, triphenylmethanol, and 1-phenylethanol, were effectively hydrogenolyzed to the corresponding hydrocarbons.

It is better to die on your feet than to live on your knees.......
-Emiliano Zapata-

Rhodium
(Chief Bee)
09-27-04 17:36
No 533407
User Picture       Reductions with modified borohydride reagents
(Rated as: excellent)

Chemoselective and stereoselective reductions with modified borohydride reagents
Guy Windey, Karl Seper, John H. Yamamoto
PharmaChem, 15-18 (2002) (https://www.rhodium.ws/pdf/selective.reductions.modified.borohydride.pdf)

Abstract
Sodium Borohydride (NaBH₄) is the preferred reducing agent for chemoselective reductions of aldehydes and ketones. It is sometimes forgotten, however, that Sodium Borohydride can be easily modified to form either a stronger or more selective reducing agent. And under the appropriate conditions, this versatility expands to include stereoselective reductions. This article will examine a few typical industrial examples showing Sodium Borohydride as a chemoselective and and stereoselective
reducing agent.
____ ___ __ _

Enantioselective Borohydride Reduction Catalyzed by Optically Active Cobalt Complexes
Tohru Yamada,Takushi Nagata, Kiyoaki D. Sugi, Kiyotaka Yorozu, Taketo Ikeno, Yuhki Ohtsuka, Daichi Miyazaki, Teruaki Mukaiyama
Chemistry - A European Journal, 9(18), 4485-4509 (2003) (https://www.rhodium.ws/pdf/nabh4.chiral.cobalt-complexes.pdf)

Abstract
The highly enantioselective borohydride reduction of aromatic ketones or imines to the corresponding alcohols was developed in the presence of a catalytic amount of an optically active cobalt(II) complex catalyst. This enantioselective reduction is carried out using a precisely premodified borohydride with alcohols such as tetrahydrofurfuryl alcohol, ethanol and methanol. High optical yields are obtained by choosing the appropriate alcohol as modifiers and a suitable β-ketoiminato ligand of the catalyst. The enantioselective borohydride reduction has been successfully applied to the preparation of optically active 1,3-diols, the stereoselective reduction of diacylferrocenes, and dynamic and/or kinetic resolution of 1,3-dicarbonyl compounds.

^{The Hive - Clandestine Chemists Without Borders}

Rhodium
(Chief Bee)
09-27-04 18:21
No 533416
User Picture       Org. React. 59: Reductive amination w/ BH3 & MBH4
(Rated as: excellent)

_{If anyone has access to the full version of Organic Reactions online, feel free to post the missing tables not available in the DjVu file below.}

Reductive Aminations of Carbonyl Compounds with Borohydride and Borane Reducing Agents
Ellen W. Baxter, Allen B. Reitz, John Wiley and Sons, Inc. (2002)
Org. React. 59, Chapter 1, pp. 1-57 + 660-714 (https://www.rhodium.ws/djvu/boros.djvu) (sans tables, provided by lugh)
DOI:10.1002/0471264180.or059.01

_{Abstract
1. Introduction
2. Mechanism and Stereochemistry
3. Scope and Limitations: The Reducing Agent
4. Scope and Limitations: The Carbonyl Component
5. Scope and Limitations: The Amine Component
6. Intramolecular Reductive Aminations
7. Side Reactions
8. Failed Reactions
9. Reductive Aminations on a Solid Support
10. Tandem Reactions
11. Comparison with Other Methods
12. Experimental Conditions
13. Experimental Procedures
14. Tabular Survey
15. Acknowledgments
References}

_{Keywords: organic reaction(s); organic synthesis; reaction(s); synthesis; reductive amination; condensation; alkylation; reductive alkylation; reduction; amination; carbonyl; amine; reducing agent(s); borohydride; borane; carbon-nitrogen bond(s); CN bond(s)}

Abstract
Reductive amination is an important tool for synthetic organic chemists in the construction of carbon-nitrogen bonds. This reaction, also termed reductive alkylation, involves condensation of an aldehyde or ketone with an amine in the presence of a reducing agent. A wide variety of substrates can be used including aliphatic and aromatic aldehydes and ketones, and even benzophenones. A range of amines from ammonia to aromatic amines, including those with electron-withdrawing substituents, can be employed. For particularly sluggish reactions, such as those involving weakly electrophilic carbonyl groups, poorly nucleophilic amines, or sterically congested reactive centers, additives such as molecular sieves or Lewis acids are often useful.

This chapter focuses on those conditions in which the carbonyl component, amine, and reducing reagent react in the same vessel. This review is restricted to reductive aminations using borohydride and borane reducing agents. This chapter concentrates on reductive amination chemistry mediated by borohydride and other boron-containing reducing agents from 1971, the year when sodium cyanoborohydride was introduced, through the middle of 1999. In addition to reductive aminations of aldehyde and ketone substrates, reactions of related structures including acetals, aminals, ketals, carboxylic acids, nitriles, and dicarbonyls that form a nitrogen-containing ring are reviewed. Intramolecular processes in which the substrate contains both the carbonyl and amine moieties are described. The intramolecular variant is a useful method for preparing cyclic amines. All of the various boron-containing hydride sources in reductive aminations, including labeled metal hydrides, are reviewed. Instances of reductive aminations that failed are described. Applications of this method to a solid support in parallel synthesis in combinatorial chemistry as well as reductive aminations that proceed in tandem with a second reaction such as reductive lactamizations are discussed.

1. Introduction

Reductive amination is an important tool for synthetic organic chemists in the construction of carbon-nitrogen bonds. This reaction, also termed reductive alkylation, involves condensation of an aldehyde or ketone with an amine in the presence of a reducing agent as illustrated in Eq. 1. A wide variety of substrates

can be used including aliphatic aldehydes and ketones, aromatic aldehydes and ketones, and even benzophenones. Further, a range of amines from ammonia to aromatic amines, including those with electron-withdrawing substituents, can be employed. For particularly sluggish reactions, such as those involving weakly electrophilic carbonyl groups, poorly nucleophilic amines, or sterically congested reactive centers, additives such as molecular sieves or Lewis acids are often useful.

Reductive aminations have been reviewed on numerous occasions, (1-17) and this chapter focuses on those conditions in which the carbonyl component, amine, and reducing agent react in the same vessel. The reduction of a preformed, isolated species such as an imine or oxime is not covered. This review is also restricted to reductive aminations using borohydride and borane reducing agents. Reactions carried out with other metal hydrides or inorganic reducing agents in addition to catalytic hydrogenations, Leuckart conditions, and enzymatic reductive aminations are not included. A review summarizing reductive alkylation of proteins has been published recently, (18) and these substrates are not covered here. This chapter concentrates on reductive amination chemistry mediated by borohydride and other boron-containing reducing agents from 1971, the year when sodium cyanoborohydride was introduced by Borch and coworkers, (19) through the middle of 1999. Although we have been as inclusive as possible, there are almost certainly additional references that we inadvertently missed. We apologize in advance to those authors who do not see their own contributions cited here.

In addition to reductive aminations of aldehyde and ketone substrates, we review reactions of related structures including acetals, aminals, ketals, carboxylic acids, and nitriles as well as dicarbonyl substrates that form a nitrogen-containing ring. Intramolecular processes in which the substrate contains both the carbonyl and amine moieties are described. In these reactions, one of the components is typically masked, and reductive amination occurs upon deprotection. The intramolecular variant is a useful method for preparing cyclic amines.

While sodium cyanoborohydride is the best known hydride reagent for reductive alkylations, sodium borohydride is often used as well. (20) Sodium triacetoxyborohydride is now widely used because it is nontoxic and generally does not reduce the carbonyl group prior to imine formation. (21) Amine boranes such as borane-pyridine are also employed in reductive aminations. (22) We review all of the various boron-containing hydride sources in reductive aminations in this chapter, including labeled metal hydrides such as sodium cyanoborodeuteride.

Instances where reductive aminations fail are described, including cases when reaction is not observed and also where side products appear, such as alcohols and bis-alkylated amines.

Finally, we discuss the application of this method to a solid support in parallel synthesis and combinatorial chemistry as well as reductive aminations that proceed in tandem with a second reaction such as in reductive lactamizations.

The Tabular Survey at the end of the chapter includes thousands of specific reactions and applications for reductive aminations, including sections on aldehydes, ketones, dicarbonyl substrates, tricarbonyl substrates, carboxylic acids, nitriles, intramolecular reductive aminations, reductive lactamizations, and Michael-type additions and reductive aminations.

^{The Hive - Clandestine Chemists Without Borders}

indole_amine
(Newbee)
09-27-04 18:48
No 533421
User Picture       C=N and C=O reduction via cobalt/borohydride (2)

New and efficient catalysts for enantioselective borohydride reduction of ketones and imines
Takushi Nagata, Kiyoaki D. Sugi, Kiyotaka Yorozu, Tohru Yamada and Teruaki Mukaiyama
"Catalysis Surveys from Japan" Volume 2, Issue 1, 47–57 (1998)

Abstract
Optically active aldiminato cobalt(II) complexes have been found to catalyze the enantioselective reduction of ketones with sodium borohydride affording the corresponding optically active secondary alcohols in high chemical yields with high enantioselectivities. The enantioselective borohydride reduction is also applicable to not only C=O bonds in aromatic ketones but also to C=N bonds in aromatic imines.

(essentially the same as the second paper in Post 533407 (Rhodium: "Reductions with modified borohydride reagents", Novel Discourse))

_{indole_amine}

indole_amine
(Hive Bee)
09-27-04 21:11
No 533435
User Picture       triacetoxyborohydride C=O reduction
(Rated as: good read)

Reactions of Sodium Borohydride in Acetic Acid: Reductive Amination of Carbonyl Compounds
(A. V. Panfilov, Yu. D. Markovich, A. A. Zhirov, I. P. Ivashev, A. T. Kirsanov, V. B. Kondrat'ev)
Pharmaceutical Chemistry Journal, Volume 34, Issue 7, July 2000, Pages 371 - 373
(translation of the original russian article, which was originally published in Khimiko-Farmatsevticheskii Zhurnal)

"Sodium borohydride is widely used for the reduction of carbonyl-containing compounds to alcohols. Previously, we demonstrated that sodium borohydride can also be successfully employed for the reductive amination of carbonyl compounds by inorganic acid salts of ammonia and primary and secondary amines. The purpose of this work was to study the interaction of carbonyl compounds with ammonia, primary amines, and sodium borohydride in acetic acid according to the scheme R'R-C=O + R''-NH₂ ---(NaBH₄/CH₃COOH--> R'R-CH-NH-R'' (...)"

_{indole_amine}

indole_amine
(Hive Bee)
09-27-04 21:23
No 533437
User Picture       salen complex catalyzed borohydride reductions
(Rated as: good read)

Symmetric Borohydride Reduction of Ketones by Unsymmetrical Co(II) Chiral Salen Complexes
(Geon-Joong Kim)
Reaction Kinetics and Catalysis Letters Volume 69, Issue 1, Jan 2000 (183-190)

Abstract
"New unsymmetrical chiral Co(II) salen complexes were synthesized and the efficiency of these catalysts was examined in the enantioselective reduction of aromatic ketones. The higher level of enantioselectivity was attainable over chiral Co(II) salen complexes prepared from salicylaldehyde and 2-formyl-4,6-di-tert-butylphenol derivatives."

Application of new unsymmetrical chiral Mn(III), Co(II,III) and Ti(IV) salen complexes in enantioselective catalytic reactions
(Geon-Joong Kim)
Catalysis Letters Volume 63, Issue 1, Jan 1999 (83-90)

Abstract
"New unsymmetrical chiral salen complexes were synthesized and the efficiency of Mn(III), Ti(IV), Co(II) and Co(III) type catalysts were examined in the enantioselective epoxidation of styrene and a-methylstyrene, the trimethylsilylcyanation of benzaldehyde, the borohydride reduction of aromatic ketones and asymmetric hydrolysis of epoxides to diols, respectively. A very high level of enantioselectivity was attainable over the unsymmetrical chiral salen complexes prepared mainly from salicylaldehyde and 2-formyl-4,6-di-tert-butylphenol derivatives. Enantiomeric excess of the corresponding reaction product obtained using unsymmetrical chiral salen catalysts was generally higher than that over conventional symmetric chiral salen catalysts."

indole_amine
(Hive Bee)
09-27-04 21:42
No 533442
User Picture       asymmetrically induced borohydride reductions (!)

Asymmetric Induction by beta-Cyclodextrins in NaBH4 Reduction of Ketones
(Kwanghee Koh Park, Woo-Jeon Sim, Joon Woo Park)
Journal of Inclusion Phenomena, Volume 27, Issue 1, January 1997, Pages 41 - 48

"Asymmetric reduction of various prochiral ketones was achieved with sodium borohydride utilizing в-CD or its derivative, mono-6-deoxy-6-[N-(2-aminoethyl)]amino-в-CD (в-CD-en) as a chiral template. It was found that pre-equilibrium between ketone and в-CD derivative and low reaction temperature increase asymmetric induction. The extent of asymmetric induction and the absolute configuration of the resulting secondary alcohols are highly dependent upon the nature of the ketones and also в-CD derivatives. A mechanistic scheme is suggested to explain the dependency."

_{indole_amine}

Lego
(Hive Bee)
11-11-04 21:52
No 541087
User Picture       Reductive amination with alpha-picoline-borane
(Rated as: good read)

One-pot reductive amination of aldehydes and ketones with alpha-picoline-borane in methanol, in water, and in neat conditions
Shinya Sato, Takeshi Sakamoto, Etsuko Miyazawa and Yasuo Kikugawa
Tetrahedron, 2004, 60(36), 7899-7906
DOI:10.1016/j.tet.2004.06.045

Abstract: A one-pot reductive amination of aldehydes and ketones with amines using alpha-picoline-borane as a reducing agent is described. The reaction has been carried out in MeOH, in H₂O, and in neat conditions in the presence of small amounts of AcOH. This is a highly efficient and mild procedure that is applicable for a wide variety of substrates. In particular, this is the first successful demonstration that this type of reaction can be carried out in water and in neat conditions.

The tendency is to push it as far as you can

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