Lithium borohydride aldehydes

Complex hydrides can be used for the selective reduction of the carbonyl group although some of them, especially lithium aluminum hydride, may reduce the a, -conjugated double bond as well. Crotonaldehyde was converted to crotyl alcohol by reduction with lithium aluminum hydride [55], magnesium aluminum hydride [577], lithium borohydride [750], sodium boro-hydride [751], sodium trimethoxyborohydride [99], diphenylstarmane [114] and 9-borabicyclo[3,3,l]nonane [764]. A dependable way to convert a, -un-saturated aldehydes to unsaturated alcohols is the Meerwein-Ponndorf reduction [765]. 

Chemical reduction of aromatic aldehydes to alcohols was accomplished with lithium aluminum hydride [5i], alane [770], lithium borohydride [750], sodium borohydride [757], sodium trimethoxyborohydride [99], tetrabutylam-monium borohydride [777], tetrabutylammonium cyanoborohydride [757], B-3-pinanyl-9-borabicyclo[3.3.1]nonane [709], tributylstannane [756], diphenylstan-nane [114], sodium dithionite [262], isopropyl alcohol [755], formaldehyde (crossed Cannizzaro reaction) [i7i] and others. 

When the reaction between a trialkylborane and carbon monoxide (8-24) is carried out in the presence of a reducing agent such as lithium borohydride or potassium triisopropoxy-borohydride, the reduction agent intercepts the intermediate 73, so that only one boron-to-carbon migration takes place, and the product is hydrolyzed to a primary alcohol or oxidized to an aldehyde.333 This procedure wastes two of the three R groups, but this problem can be avoided by the use of B-alkyl-9-BBN derivatives (p. 785). Since only the 9-alkyl group... 

Lithium borohydride is intermediate in activity as a reducing agent between lithium aluminium hydride and sodium borohydride. In addition to the reduction of aldehydes and ketones it will readily reduce esters to alcohols. It can be prepared in situ by the addition of an equivalent quantity of lithium chloride to a 1m solution of sodium borohydride in diglyme. Lithium borohydride should be handled with as much caution as lithium aluminum hydride. It may react rapidly and violently with water contact with skin and clothing should be avoided. 

In 1972 Link and Bernauer (69) published a synthesis of (+)-isopilosine and of (+)-pilocarpine, and then obtained (—)-epiisopilosine as a by-product. The readily available ester 53 was converted in two steps to the aldehyde (54), which on Stobbe condensation with succinic ester gave the half-ester acid salt 55. Lithium borohydride reduction followed by prolonged acid treatment gave ( )-pilosinine [( )-32], together with 2,3-dehydropilosin-... 

LiBH4 (lithium borohydride) Tetrahydrofuran OtoRT ester —> alcohol ketone —> alcohol aldehyde —> alcohol... 

In contrast to the usual reaction of aromatic aldehydes with cyclic ketones o-nitrobenzaldehyde condenses with 17-ketones to produce good yields of seco-acids, a reaction which has been applied to the preparation of 16-oxa-steroids. Thus, 3 -hydroxy-5a-androstan-17-one or its acetate affords the seco-steroid (153), which can be oxidised either as the free acid by ozone and alkaline hydrogen peroxide to the diacid (155) or, as its methyl ester (154), with chromium trioxide to the monomethyl ester (156). Diborane reduction of the diacid (155) or lithium aluminium hydride reduction of the dimethyl ester (157) gave the trans-diol (158), cyclised with toluene-p-sulphonic acid to 16-oxa-androstan-3)5-ol (159) or, by oxidation with Jones reagent to the lactone (152) (as 3-ketone) in quantitative yield. This lactone could also be obtained by lithium borohydride reduction of the monomethyl ester (156), whilst diborane reduction of (156) and cyclisation of the resulting (151) afforded the isomeric lactone (150). The diacid (155) reacted with acetic anhydride to afford exclusively the cis-anhydride (161) which was reduced directly with lithium aluminium hydride to the cis-lactone (160) or, as its derived dimethyl ester (162) to the cis-diol (163) which cyclised to 16-oxa-14)5-androstan-3) -ol (164). 

Thiomethyl-PS 6b, prepared from Merrifield s resin la by reaction with thioacetate followed by reduction, can be acylated to give thioesters [263]. The resin-bound thioesters have been converted to silyl enol ethers, which were shown to form aldol products that could be released from the resin by three methods [264], Thus, reduction with lithium borohydride or diisobutylaluminum hydride (DIBAL) gave diols and aldehydes, respectively alternatively, base hydrolysis afforded carboxylic acids. Resin 6b thereby extends the range of functional groups available compared with cleavage of related molecules from an ester anchor. 

Lithium borohydride supported on zeolite A or X will bring about the selective reduction of aldehydes without reducing any ketones that may be present [102]. Lithium aluminium hydride in the presence of silica gel reduces ketones rapidly and in high yield without affecting cyano or nitro groups (e.g. equation 4.19) [103]. The same reagent also selectively reduces carboxylic esters when other reducible groups are present and facilitates the formation of hydroxyesters from ketoesters [104]. 

In many cases, the carboxyl portion of the amino acid starting material is converted to an aldehyde, allowing several reactions that are not available to carboxylic acids. An example of this approach is the conversion of N-Boc alanine (5.4) to N-Boc alinal (5.5X via conversion to the ester and reduction with lithium borohydride. The next step will be a common feature of this and succeeding chapters. Oxidation of the alcohol moiety in 5.5 to an aldehyde, in this case using S03 pyridine in DMSO, allowed condensation with sodium cyanide to give a cyanohydrin. Hydrol-... 

Chemoselective reduction of aldehydes in the presence of ketones has been performed with lithium borohydride adsorbed on molecular sieve zeolites of types A and X. Although it is tempting to postulate that only aldehydes can penetrate into the pores containing the borohydride, preliminary evidence does not seem to support this idea. The more unusual reverse chemoselectivity, that is reduction of only the ketones in ketone-aldehyde mixtures, has been demonstrated for sodium borohydride in the presence of lanthanoid cations (Ln ) such as Ce (Scheme 7). Lanthanoid salts are known to catalyse the... 

This was exercised with ester 266. The magnesium complex formed in the Grignard reaction was stereoselectively reduced with lithium borohydride while the aldehyde-aluminum complex formed in the low temperature DIBAL reduction is also stereoselectively attacked by the Grignard reagent [102]. 

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