Epoxides lithium diisopropylamide

Recyclization of epoxide 87 with lithium diisopropylamide (LDA) in THF at —65 °C (Equation 36) gives oxepan 88 <1998JOC9728>. 

Eliminations of epoxides lead to allyl alcohols. For this reaction to take place, the strongly basic bulky lithium dialkylamides LDA (lithium diisopropylamide), LTMP (lithium tetramethylpiperidide) or LiHMDS (lithium hexamethyldisilazide) shown in Figure 4.18 are used. As for the amidine bases shown in Figure 4.17, the hulkiness of these amides guarantees that they are nonnucleophilic. They react, for example, with epoxides in chemoselective E2 reactions even when the epoxide contains a primary C atom that easily reacts with nucleophiles (see, e.g., Figure 4.18). 

Asami and coworkers discovered that the chiral lithium amide 4 was more reactive toward epoxides than lithium diethylamide (LiNEt2) or lithium diisopropylamide (LDA) argil° pje reasonecj at an achiral lithium amide could be used to regenerate the chiral... 

The a-protons of iron acyl complexes are acidic and these can be deprotonated with Lithium diisopropylamide (LDA) or with n-butyllithimn. Thus the corresponding enolates are readily functionalized and undergo reaction with alkyl halides, aldehydes, disulfides, trimethylsilyl chloride, and epoxides to afford the corresponding a-derivatized products. " Early work on racemic complexes revealed that these transformations occur in a highly diastereoselective fashion,... 

Organometallic addition to the /V-methoxy-A -methylamide (15) also affords an exceptionally stable tetrahedral intermediate (16) and carbonyl-protecting group, first used in the synthesis of X-206. Deprotonation of the hydrazone in intermediate (16) was subsequently carried out with lithium diisopropylamide. The resulting dianion initiated a novel attack upon epoxide (17) and in the ensuing transformation was followed by tetrahydrofuran ring formation as depicted, in 71% yield, all in one pot (Scheme 4). 

For many years the formula 559 for santolinenone has been suspect. The last nail in its coffin has finally been driven by Guella et al., who, after disposing of a certain amount of published rubbish, have synthesized 559 from 1-menthene epoxide (560), by ring opening (lithium diisopropylamide) and oxidation (silver carbonate on Celite). They carefully described 559, the corresponding alcohols, and the dimer of 559, so there is no further excuse for inadequate characterization of this pseudo-product. 

Successful application of the Mitsonobu epimerization procedure to an eudesmanic alcohol 44 to bring about inversion of configuration at C(l) is the crucial step in the Harapanhalli synthesis of erivanin (50) from santonin (Scheme 7) [16]. Reduction of enone 43, prepared from santonin in 10 steps, with sodium borohydride furnished the )8-alcohol 44 as the sole product. This product results from the approach of the hydride anion from the less hindered Of-face of the molecule. The chemical modification of the C(3)-C(4) double bond to give a 3a-hydroxy-A4-i4 rnoiety was accomplished via the epoxide 46 and its rearrangement in a basic medium. Epoxidation of 44 with MCPA yielded only one product without any directing effect exerted by the homoallylic alcohol. Treatment of 46 with lithium diisopropylamide (EDA) afforded l-e/>/-erivanin (47). For the synthesis of erivanin (50), epimerization at C(l) prior to the A -modification sequence was required. Attempts to epimerize this carbon atom in 44 by acetolysis of the tosyl derivative 45 were unsuccessful as they led to eliminated product 13 (Scheme 3). 

In the presence of lithium diisopropylamide the anhydride 2 reacts with the epoxide of ethyl 5-methyl-4-hexenoate 270, forming compound 271. The latter is converted on silica gel in a neutral medium into the dihydrofuran derivative 272, which undergoes spontaneous cyclization to the derivative of dihydrofuroquinolinone 273 (yield 33%) [179],... 

Andersson developed chiral lithium amide 1 for the enantioselective base-mediated transformation of /neso-epoxides to allyl alcohols (Scheme 2.2). The combined use of lithium diisopropylamide (LDA) and 1,8-diazabicy-clo[5.4.0]undec-7-ene (DBU) with 1 was essential, and cyclic meso-epoxides 2 gave the corresponding 2-cycloalken-l-ol derivatives 3 with high enantioselectivities. 

The stereochemical information is introduced by (J )-methyl p-toluenesulfoxide 110. This compound is deprotonated with lithium diisopropylamide and reacted with a-chloro methylacetate 109 to give a-chloroketone 111. This ketone when reacted with diisobutylaluminum hydride at —78°C gives (J )-chlorohydrine 112, whereas reaction of ketone 111 with diisobutylaluminum hydride and zinc chloride gives the corresponding (S)-chlorohydrine 113. Treatment of both chlorohydrines with potassium carbonate resulted in the formation of epoxides 114 and 116. These can now be reacted with either (Z)- or (T)-vinyl cuprates to give the desired homoallylic alcohols 115 and 117 in diastereomeric excesses around 90%. 

---