Diisobutylaluminum hydride, reaction with esters

Digitoxigenin, structure of, 1097 Digitoxin, structure of, 989 Dihalide, alkynes from, 261 Dihedral angle, 94 Diiodomelhane. Simmons-Smith reaction with, 228-229 Diisobutylaluminum hydride, reaction with esters, 812 structure of, 699 Diisopropylamine, pK.d of, 923 1,3-Diketone, pfCa of, 852 Dimethyl disulfide, bond angles in, 20 structure of, 20 Dimethyl ether, electrostatic... 

Perlmutter used an oxymercuration/demercuration of a y-hydroxy alkene as the key transformation in an enantioselective synthesis of the C(8 ) epimeric smaller fragment of lb (and many more pamamycin homologs cf. Fig. 1) [36]. Preparation of substrate 164 for the crucial cyclization event commenced with silylation and reduction of hydroxy ester 158 (85-89% ee) [37] to give aldehyde 159, which was converted to alkenal 162 by (Z)-selective olefination with ylide 160 (dr=89 l 1) and another diisobutylaluminum hydride reduction (Scheme 22). An Oppolzer aldol reaction with boron enolate 163 then provided 164 as the major product. Upon successive treatment of 164 with mercury(II) acetate and sodium chloride, organomercurial compound 165 and a second minor diastereomer (dr=6 l) were formed, which could be easily separated. Reductive demercuration, hydrolytic cleavage of the chiral auxiliary, methyl ester formation, and desilylation eventually led to 166, the C(8 ) epimer of the... 

Polystyrene-bound carboxylic esters have been reduced with diisobutylaluminum hydride or lithium aluminum hydride. Use of the latter reagent can, however, lead to the formation of insoluble precipitates, which could readily cause problems if reactions are performed in fritted reactors. An alternative procedure for reducing carboxylic esters to alcohols involves saponification, followed by activation (e.g. as the mixed anhydride) and reduction with sodium borohydride (Entries 10 and 11, Table... 

The Homer-Emmons addition of dialkyl carboalkoxymethylenephosphonates to aldehydes [22] has been widely used to generate a,p-unsaturated esters which, in turn, can be reduced to allylic alcohols. Under the original conditions of the Homer-Emmons reaction, the stereochemistry of the oc,(3-unsaturated ester is predominantly trans and therefore the trans allylic alcohol is obtained upon reduction. Still and Gennari have introduced an important modification of the Homer-Emmons reaction, which shifts the stereochemistry of the a,[i-unsaturated ester to predominantly cis [23], Diisobutylaluminum hydride (DIBAL) has frequently been used for reduction of the alkoxycarbonyl to the primary alcohol functionality. The aldehyde needed for reaction with the Homer-Emmons reagent may be derived via Swern oxidation [24] of a primary alcohol. The net result is that one frequently sees the reaction sequence shown in Eq. 6A. 1 used for the net preparation of 3E and 3Z allylic alcohols. 

A-f-Butoxycarbonylphenylalanine methyl ester (3.6 mmol) was dissolved in 15 ml toluene, then cooled to -78° C, and treated with the dropwise addition of 9.0 ml 1M solution of diisobutylaluminum hydride in toluene over 5 minutes. After 1 hour, the reaction was slowly quenched with 1 ml methyl alcohol, and then poured into a cooled aqueous solution of potassium sodium tartrate. The mixture was stirred 2 hours, then extracted with diethyl ether, washed with water and brine, dried over Na2S04, and concentrated to a colorless oil. The oil was purified by chromatography using silica gel with 20% EtOAc/heptane and the product isolated in 88% yield as a white solid. 

Diisobutylaluminum phenylselenolate (39), which is prepared in situ by the reaction between diphenyl diselenide and diisobutylaluminum hydride (DIBALH) [67], is also a useful nucleophilic selenium reagent (Scheme 37). For example, 39 reacts with oxime sulfonates to produce selenoimidic esters... 

Just as considerable effort has been exerted to utilize LiAlH4 or its derivatives for the selective reduction of amides to aldehydes, so too has much exertion gone into the use of diisobutylaluminum hydride. This area has been reviewed. " With DIBAH itself in diethyl ether at 0 °C, A -methylanilides furnish aldehydes in yields of 25-70%, the remainder of the reaction products being mostly amines. The yield of aldehyde drops severely above 0 °C. DIBAH, tempered by the addition of various amines, has been discussed in Section 1.11.2 (ref. 5) and Section 1.11.4 (ref. 60). One of these reagents, bis(4-methyl-l-piperazinyl)aluminum hydride has been recommended for the reduction of dimethylamides (and other amides) to aldehydes in 65-80% yield." The hydride is mild enough for it to be necessary to reflux the amide in diethyl ether with the reagent for several hours. It should be noted that under such conditions acids and esters will be reduced also. 

Quinolines generally produce 1,2-dihydroqulnolines with aluminum hydrides. Diisobutylaluminum hydride and Red-Al have been used to reduce quinolines and quinoline-A -boranes (42 Scheme 9). The reactions are believed to proceed via aminoalanes or boranes and the dihydroquinolines produced are quenched and trapped as the carbamates by the addition of chloroformate esters. Minor amounts of 1,4-dihydro- and 1,2,3,4-tetrahydro-quinolines are also formed. The possession of a 2-substituent hinders reaction. At low temperatures the kinetic product, i.e. (43), is favored, but at higher temperatures reduction at the 4-position predominates which subsequently produces the tetrahydro derivative (44). A similar approach has been employed with isoquinoline, generating 1,2-disubstituted tetrahydroisoquinolines (45 Scheme 9). ... 

Formation of sulfide with concurrent ester hydrolysis was achieved when various Cj cyclopropyl cephalosporin 5-oxide 2,2,2-trichloroethyl esters were treated with phosphorus trichloride followed by zinc under acidic conditions. Sulfoxide reduction also occurred on treatment of cyclopropyl phenyl sulfoxide with a mixture of benzenethiol and chlorotrimethylsilane in chloroform to give cyclopropyl phenyl sulfide in 76% yield and on reaction of various substituted cyclopropyl phenyl sulfoxides with diisobutylaluminum hydride. ... 

When the benzyl ether derivative (Z)-16 of (Z)-13 is employed in an analogous reaction, cycloisomerization occurs to yield a diastereomeric mixture of methyl 6-benzyloxy-3a-methyl-3-methyleneoctahydropentalene-l-carboxylates (17A, B) in a combined yield of 43%. The products could be separated after reduction of the ester groups with diisobutylaluminum hydride which yielded a 5 1 mixture of the corresponding hydroxymethyl derivatives (36% combined overall yield). 

Construction of the suitably substituted geranic acid for making the furan ring has been effected too. For example, Poulter et al. have prepared the substituted geranate 865 by reaction of 4-methyl-3-pentenylcopper with the acetylenic ester 866. The ester 865 then underwent cyclization in the presence of acid to the lactone 867, related to scobinolide (161), and the action of acid on the lactol produced from 867 with diisobutylaluminum hydride gave perillene (849). The lactone 867 has also been prepared by a slightly different method the C9 alcohol 868 was made (in poor yield) from isobutenol and prenyl chloride with butyllithium. The extra carbon atom was introduced by the action of sodium cyanide on the epoxide of 868, and hydrolysis of the cyano group followed by dehydration yielded the lactone 867. The dimethylthioacetal of 867 has been used to synthesize perillene (849). This thioacetal was made from the suitably substituted ketene thioacetal 869 and dimethylsulfonium methylide. Thus the ketene thioacetal 870 (readily prepared from acetone, carbon disulfide, and sodium amylate, followed by methylation °) can be prenylated with lithium... 

Complex hydrides have been used rather frequently for the conjugate reduction of activated dienes . Just and coworkers found that the reduction of a,fi-unsaturated ketene S,S-acetals with lithium triethylborohydride provided mixtures of 1,4- and 1,6-reduction products which were transformed into enals by treatment with mercuric salts (equation 27). Likewise, tetrahydro-3//-naphthalen-2-ones can be reduced with L-Selectride to the 1,6-reduction products this reaction has been utilized in the stereoselective synthesis of several terpenes, e.g. of (/J)-(—)-ligularenolide (equation 28) . Other methods for the conjugate reduction of acceptor-substituted dienes involve the use of methylcopper/diisobutylaluminum hydride and of the Hantzsch ester... 

The procedure outlined above describes the selective, retentive, p-coupling of (Z)-2,3-dibromopropenoic acid ethyl ester with (trimethylsilyl)acetylene employing the palladium-modified version of the Castro-Stephens reaction.4 5 The dibromide starting material is readily available by bromination of ethyl propiolate (Procedure A), as described by Trippett and Hall.2 The coupling product has been shown to be a versatile precursor for the synthesis of variously substituted enynes and enediynes. For example, a second acetylene may be introduced into the a-position under modified coupling conditions. Alternatively, reduction of the ester with diisobutylaluminum hydride and protection of the resultant alcohol with tert-butyldiphenylsilyl chloride affords a vinyl bromide that can be metalated and trapped with various electrophiles. These procedures have been used on the gram and multigram scale.5... 

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. 

---