Borohydride resin

Many reductions have also been conducted under similar conditions using the simple immobilised borohydride resin. The majority of these reactions have been conducted because the corresponding room temperature reaction proved to be very slow. Again enhancements in rates and overall yields have been noticed. 

Abbreviations Amberlite IRA 400 borohydride resin, commercially available resin for selective reduction of a,/3-unsaturated aldehydes and ketones DBU, 1,8-diazabicyclo [5.4.0]undec-7-en DCM, dichloromethane DMF, dimethylformamide EtOAc, ethyl acetate Et2NH, diethylamine Et3N, triethylamine HBr, hydrobromic acid HC1, hydrochloric acid MS, mass spectrometry MeOH, methyl alcohol NH4OH, ammonium hydroxide NaBHj, sodium borohydride NaOH, sodium hydroxide NaOMe, sodium methanolate PAMAM, polyaminoamide resin (commercially available) RT, room temperature THF, tetrahydrofuran. 

Dibenzylamine (38). A solution of benzaldehyde (0.5 mmol) in isopropanol (1.5 ml) was treated with benzylamine (0.8 mmol). The resulting reaction mixture was shaken at RT for 2 h. Then Amberlite IRA 400 borohydride resin (2.5 mmol NaBFLt/g resin) was added and the mixture was shaken at RT for 24 h. DCM (1.5 ml) was introduced followed by the addition of the acetoacetoxyethyl metacrylate resin (37). The contents were shaken at RT for 36 h. Upon filtration of the resin followed by solvent evaporation of the filtrate, pure benzylamine-free dibenzylamine (38) was obtained. 

Reagents and conditions (i) MeOH, r.t., 1 h (ii) Amberlite IRA-400 borohydride resin, r.t (iii) polystyrene carboxaldehyde 11, CH2C12, overnight (vi) filter (v) ethanol-free CHC13,... 

Reduction of the nitro group and halides. Amines are obtained in good yields. The reduction can also be performed by a reagent generated from borohydride resin. The latter reagent converts alkyl bromides and iodides to the hydrocarbons, whereas chlorides, tosylates, esters, and nitriles are not affected. 

Several other examples have been published O- including the one-pot solid-phase cleavage of a-diols to primary alcohols as shown in Scheme 3.5.9. In this successful application, a 1 1 mixture of periodate- and borohydride-resins were filled into a column and an aqueous solution of nucleoside was slowly pumped through. The intermediately formed, unstable dialdehydes were reduced in situ to the corresponding diols. Yields were good for the base being adenine (70%), cytosine (79%) and uracil (73%) and moderate for guanidine (40%). 

Sodium borohydride has been incorporated into alumina (Hodosan and Servan, 1969), cellulose matrices (Perrier and Benerito, 1976), and ion-exchange resins (Gibson and Bailey, 1977). The latter reagent was readily prepared using Amberlite IRA-400 and Amberlyst A-26. A more extensive survey of the properties of this material has been published (Cook et al., 1978 Cook, 1978). The borohydride resin (Resin-Borohydride) is a developmental product of Ventron Corporation, Beverly, Massachusetts. 

Eda and Kurth applied a similar solid-phase combinatorial strategy for synthesis of pyridinium, tetrahydropyridine, and piperidine frameworks as potential inhibitors of vesicular acetylcholine transporter. One member of the small library produced was prepared from amino-functionalized trityl resin reacting with a 4-phenyl Zincke salt to give resin-bound product 62 (Scheme 8.4.21). After ion exchange and cleavage from the resin, pyridinium 63 was isolated. Alternatively, borohydride reduction of 62 led to the 1,2,3,6-tetrahydropyridine 64, which could be hydrogenated to the corresponding piperidine 65. 

See Wallace, O.B. Springer, D.M. Tetrahedron Lett., 1998, 39, 2693 for cleavage of thiol esters to thiols with NaSMe in methanol and Choi, J. Yoon, N.M. Synth. Commun., 1995, 25, 2655 for borohydride exchange resin-Pd(OAc)2 reductive cleavage of thiol esters to thiols. 

COOH or NHCOCH3, for example, 2-phenyl-l-butene. Enantioselective reduction of certain alkenes has also been achieved by reducing with baker s yeast. Hydrogenation with Ni2B on borohydride exchange resin (BER) has also been... 

Triple bonds can also be selectively reduced to double bonds with DIBAL-H, " with activated zinc (see 12-36), with hydrogen and Bi2B-borohydride exchange resin, ° or (internal triple bonds only) with alkali metals (Na, Li) in liquid ammonia or a low-molecular-weight amine.Terminal alkynes are not reduced by the Na—NH3 procedure because they are converted to acetylide ions under these conditions. However, terminal triple bonds can be reduced to double bonds by the... 

NaBH4—BiCl3, borohydride exchange resin, (BER)—CuS04, Smla, and See 16-23 for methods of reducing C=0 bonds in the presence of... 

Pr)4, " borohydride-exchange resin,and formic acid. When the last is used, the process is called the Wallach reaction. Conjugated aldehydes are converted to alkenyl-amines with the amine/silica gel followed by reduction with zinc borohydride.In the particular case where primary or secondary amines are reductively methylated with formaldehyde and formic acid, the method is called the Esch-weiler-Clarke procedure. It is possible to use ammonium (or amine) salts of formic acid, " or formamides, as a substitute for the Wallach conditions. This method is called the Leuckart reaction,and in this case the products obtained are often the N-formyl derivatives of the amines instead of the free amines. Primary and secondary amines can be iV-ethylated (e.g., ArNHR ArNREt) by treatment with NaBH4 in acetic acid. Aldehydes react with aniline in the presence of Mont-morillonite KIO clay and microwaves to give the amine. Formaldehyde with formic acid converts secondary amines to the N-methyl derivative with microwave irradiation. 

BER = borohydride exchange resin Choi, J. Yoon. N.M. Svnth. Commun., 1995, 25, 2655... 

Acetophenone was reduced in methanol to 1-phenylethanol at 20 °C by boro-hydride moieties coupled to a porous polymer resin [3], In principle, four hydrogen atoms can be released from the borohydride the reactivity, however, decreases with each hydrogen atom lost Experimentally it was shown that the first two atoms mainly contribute and to the reduction the other two remain on the polymer site. 

Devaky and Rajasree have reported the production of a polymer-bound ethylenediamine-borane reagent (63) (Fig. 41) for use as a reducing agent for the reduction of aldehydes.87 The polymeric reagent was derived from a Merrifield resin and a 1,6-hexanediol diacrylate-cross-linked polystyrene resin (HDODA-PS). The borane reagent was incorporated in the polymer support by complexation with sodium borohydride. When this reducing agent was used in the competitive reduction of a 1 1 molar mixture of benzaldehyde and acetophenone, benzaldehyde was found to be selectively reduced to benzyl alcohol. 

A suspension of 414 in aquoeus dioxane was treated with proline 433a and iV-phenyl isatin 432a and the reaction mixture was heated at 80-90 °C overnight. The resin-containing cycloaddition product was reduced in aqueous tetrahydrofuran with lithium borohydride for 12 h at room temperature to afford a mixture of mainly 437 and a trace of 438 unlike in solution phase where in equal amount of 437 and 438 were produced (Scheme 99). 

Many borohydrides are highly unstable and have to be used as freshly prepared ethereal solutions. However there are instances where the polymer-supported versions are more stable e. g. an Amberlyst anion exchange resin supported borohydride and cyanoborohydride [61], polyvinylpyridine supported zinc borohydride [62] and the corresponding zirconium borohydride [63]. Such compounds, in their labeled forms, should turn out to be very useful. 

Both the hydrochloric acid and sodium borohydride contributed to the blank. The Sb (V) in the 12 N hydrochloric acid was removed by uptake on a Dowex 1-X8 anion exchange resin. Sodium borohydride was purified, after dissolution, by addition of 0.5 ml sodium hydroxide (50%) to 200 ml of 5% sodium borohydride, and subsequent filtration through a hydrochloric acid precleaned 0.45 pm Millipore membrane. 

MP borohydride catches one equivalent of the titanium catalyst, while the polystyrene-bound diethanolamine resin (PS-DEAM) can scavenge the remaining titanium catalyst. The borohydride reagent also assists in the reductive animation reaction. Final purification of the crude amine product is achieved with a polystyrene-bound toluene sulfonic acid resin scavenger that holds the amine through an ion exchange reaction, while impurities are washed off. The pure amine can be recovered with methanol containing 2M ammonium hydroxide. 

ArgoGel-MB-CHO resin (366 mg, 0.42mmol/g substitution) was placed into an Ace pressure tube (note 5). Trimethyl orthoformate (TMOF 5 mL) was added to the flask along with the primary amine (10 equiv.). The tube was capped and heated for 2h at 70°C in a rotating oven (note 6), and cooled. The TMOF solution was removed with the use of a filtration cannula, and the entire process was repeated. The resin was washed with TMOF (5 mL, lx) and anhydrous methanol (5 mL, 3 x) Anhydrous methanol (5 mL) was added to the resin, followed by the addition of sodium borohydride (133 mg, 20 equiv.). After vigorous gas evolution had ceased, the tube was capped and agitated for 8 h at room temperature. The resin was then transferred to a polypropylene reaction vessel and washed with methanol (5mL, 3 x), methanol water (1 1, 5mL, 3 x), DMF water (1 1, 5mL, 3 x), DMF (5mL, 3 x), and methylene chloride (5 mL, 3 x). 

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