Reductions with boron hydrides, sulfurated

A cis trans-mixture can be prepared by radical addition reaction of pentanal with crotonic acid followed by reductive cyclization of the resulting 7-0x0 acid with sodium boron hydride/sulfuric acid [198]. It is used in aroma compositions, e.g., for beverages. 

Boron substituents in the [l,3,2]diazaborolo[l,5- ]pyridine derivative 109 were studied. This compound was obtained via reduction of its precursor 108 with sodium amalgam (Scheme 27). The bromide attached to the boron atom was further displaced with various halide, hydride, sulfur, and carbon nucleophiles <2001JCD378>. [l,2,5]thiadiazolo[2,3- ]pyridine derivative 110 was deprotected (R = Cbz to R=H) by classical hydrogenolysis <2002AGE3866>. 

Diborane can be prepared by a variety of methods, the most common being the reduction of boron trihalides with active metal hydrides - and the reaction of hydroborate salts with boron trifluoride, tin(II) chloride, sulfuric acid, methane-sulfonic acid, orthophosphoric acid, or polyphosphoric acid. Although diborane is commercially available in bulk quantities, we have found the reaction of potassium hydroborate, KBH4, with 85% orthophosphoric acid to be convenient for the rapid preparation in a vacuum line of small quantities of this material. ... 

These two milestone syntheses were soon followed by others, and activity in this field continued to be driven by interest in the biologically active esters of cephalotaxine. In 1986, Hanaoka et al. (27) reported the stereoselective synthesis of ( )-cephalotaxine and its analog, as shown in Scheme 4. The amide acid 52, prepared by condensation of ethyl prolinate with 3,4-dimethoxyphenylacetyl chloride, followed by hydrolysis of the ethyl ester, was cyclized to the pyrrolobenzazepine 53 by treatment with polyphos-phoric acid, followed by selective O-alkylation with 2,3-dichloropropene (54) in the presence of sodium hydride. The resulting enol ether 55 underwent Claisen rearrangement on heating to provide C-allylated compound 56, whose reduction with sodium borohydride yielded the alcohol, which on treatment with 90% sulfuric acid underwent cationic cyclization to give the tetracyclic ketone 57. Presumably, this sequence represents the intramolecular version of the Wichterle reaction. On treatment with boron tribromide, ketone 57 afforded the free catechol, which was reacted with dibromometh-ane and potassium fluoride to give methylenedioxy derivative 58, suited for the final transformations to cephalotaxine. Oxidation of ketone 58... 

Reductions with sulfurated sodium boron hydride NaBH Sg... 

Benzyl Alcohols. Benzyl alcohols of nearly all kinds undergo reduction when treated with acid in the presence of organosilicon hydrides. The most obvious exception to this is the behavior of benzyl alcohol itself. It resists reduction by the action of trifluoroacetic acid and triethylsilane, even after extended reaction times.26 Reducing systems consisting of triethylsilane and sulfuric acid/acetic acid or p-toluenesullonic acid/acetic acid mixtures also fail to reduce benzyl alcohol to toluene.134 As previously mentioned, substitution of boron trifluoride for trifluoroacetic acid results in the formation of modest yields of toluene, but only when a very large excess of the silane is used in order to capture the benzyl cation intermediate and suppress Friedel-Crafts oligomerization processes.129,143... 

Reduction of aromatic carboxylic acids to alcohols can be achieved by hydrides and complex hydrides, e.g. lithium aluminum hydride 968], sodium aluminum hydride [55] and sodium bis 2-methoxyethoxy)aluminum hydride [544, 969, 970], and with borane (diborane) [976] prepared from sodium borohydride and boron trifluoride etherate [971, 977] or aluminum chloride [755, 975] in diglyme. Sodium borohydride alone does not reduce free carboxylic acids. Anthranilic acid was reduced to the corresponding alcohol by electroreduction in sulfuric acid at 20-30° in 69-78% yield [979],... 

The Harley-Mason approach to the Aspidosperma skeleton was discussed in Volume XI (p. 225), and very brief mention was made of the successful synthesis of aspidospermidine (249) using this route (241). In view of the complication involving cis/trans C/D ring stereochemistry involved in a number of other approaches, it is amazing that the Harley-Mason approach should be stereoselective. The process in question is typically reaction of the hydroxyester 560 with tryptamine to give a compound (561) having a sero-ebumane skeleton. When this compound is treated with 40% sulfuric acid or boron trifluoride etherate at 100°, the indolenine lactam 562 is produced. Lithium aluminum hydride reduction then gives racemic aspidospermidine (249 Scheme 33). 

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