With DIBAH

Problem 21.17 i What product would you expect from the reaction of butyrolactone with LiAIH4 1 With DIBAH ... 

To link the two half moieties of the molecule, a Julia-Kocienski olefmation was carried out between the C19 building block 59 (again prepared by syn-SN2 -substitu-tion of a propargylic oxirane with DIBAH) and the C20 building block 60, formed via oxidation of 58 with Mn02 (Scheme 18.19). Although this reaction initially led to the formation of the Z-isomer as the major product, the latter was readily isomerized at room temperature to the desired all-trans-polyene peridinin (6). 

Treatment of the /3-keto ester 220 with sodium ethoxide at elevated temperature triggered off an epoxide ring opening by / -elimination that was followed by the desired Knoevenagel condensation to afford the tricyclic product 206 (Scheme 34). The enone moiety in the intermediate 221 did not show a propensity for deprotonation and, therefore, the ketone carbonyl function of the enone moiety was available for a Knoevenagel condensation. The reduction of the p-keto ester (206) to the corresponding diol was the next objective. Treatment of the TES-protected -keto ester (TES-206) with DIBAH afforded the diastereomeric diols 222 and 223 in a moderate diastereoselec-tivity in favour of the undesired diastereomer 222. The diastereomers were separated and the undesired diastereomer 222 was epimerized to 223 by a sequence that consists of Mitsunobu inversion and benzoate ester reduction [98, 99]. 

The synthesis of (-t-)-benzoylselenopederic acid (569) (477) (Scheme 71), the left-hand half of pederin (147), began with (-f-)-3-keto imide 570, which was subjected to the recently developed syn-directing Zn(BH4)2 reduction (482) to give 5yn-a-methyl-3-hydroxy acid derivative 571. Imide 571, after protection of the hydroxyl group as the THP ether, was reduced with DIBAH, and the resulting aldehyde was treated with lithium enolate of tm-butyl acetate to give the p-... 

Lactones - ethers, y- and (5-Lactones can be converted into tetrahydrofuranes and tetrahydropyrancs, respectively, by a two-step procedure. The first step is the well-known reduction of lactones to lactols with DIBAH (1, 261 2, 140). The second step is deoxygenation of the alcohol with triethylsilanc and BF3 etherate.1 This reaction is compatible with several other functional groups, even including hydroxyl groups. 

It was also possible to prepare a variety of deoxy analogs of 10 and 12 by reduction of the lactone carbonyl with DIBAH, and further reduction of the corresponding lactols with Et3SiH and BF3 OEt2 (Figure 9.7). The resultant deoxoartemisinin analogs 14, substituted at 3 and 9, have been reported.26... 

Reduction of ketosulfoxides with DIBAH in the presence ofZnCl2... 

Asymmetric reduction of ketones.2 A reducing agent prepared by treatment of a mixture of SnCl2 and (S)-l-[l-methyl-2-pyrrolidinyl]methylpiperidine (11, 525, 12, 490) with DIBAH effects asymmetric reduction of prochiral ketones in 60-80% ee (equation I). 

Titanium(III) chloride-Diisobutylaluminum hydride. A black, solid lower-valent titanium reagent (1) is obtained on reduction of TiCl3 3THF with DIBAH in toluene.1... 

Ethyl lactate (4) is transformed in the first step into the corresponding THP-protected derivative, and this is reduced with DIBAH in a second reaction to give aldehyde 5. 

It is conceivable that the ester might be reduced with DIBAH or Solution... 

The ester is reduced with DIBAH in the final step to give an allylie alcohol. 

Since the electrophile is introduced adjacent to the NH protective group, substantial steric hindrance may be encountered in the following reaction steps. In case of the dimethylsulfamoyl protected imidazole-5-carboxaldehyde, a rapid isomerisation to the 4-substituted product can be induced catalytically by traces of triethylamine or by mere standing at RT for several days42. The effect of steric hindrance by the protective group was also observed in the reduction of ethyl dimethylsulfamoyl-imidazolecarboxylate with DIBAH. The 5-isomer could not be reduced, whereas the 4-isomer is reduced easily to the imidazole carboxaldehyde under the standard conditions49. 

Finally stoichiometric addition of DIBAH in a nonpolar solvent at low temperature yields the desired aldehyde 11. Overreduction to the corresponding alcohol 33 is prevented under these conditions because of the formation of the relative stable intermediate 34, which decomposes only in the course of aqueous work-up. At higher temperature and in polar solvents such as THF formation of alcohol 33 occurs. Thus, grade of reduction of esters with DIBAH can be controlled by temperature and solvent. 

Reduction of enones. Reduction of CH3Cu, prepared in situ from Cul and CH3Li in THF, with DIBAH in the presence of HMPA results in a form of copper hydride that effects efficient and selective 1,4-reduction of enals, enones, and enoates, and 1,6-reduction of dienones and dienoates. The reagent does not reduce isolated carbonyl groups or double bonds.2 It can also be used for regiospecific preparation of enol silyl ethers from an enone.2... 

A recent effort to increase the activity of NdCl3-based system comprises the use of NdCb nanoparticles. Kwag et al. succeeded in the preparation of nanosized NdCU 1.5 THF (particle size > 92 nm). The nanosized NdCl3 was prepared in THF medium by dissolution of anhydrous NdC. Nanosized NdCl3 particles were obtained in a colloidal formation step during which THF is slowly replaced by cyclohexane upon addition [ 132], Catalyst activity is inversely proportional to the size of the NdCU nanoparticles. The activation of NdCl3 nanoparticles with DIBAH/TIBA results in catalyst activities which match the activities of standard Nd-carboxylate-based ternary sys-... 

For the two catalyst systems NdV/DIBAH/EASC and NdV/TIBA/EASC the ratios of Ai/ Nd were varied over a broad range from 5 to 50. It was shown that kp depends on the nature of the cocatalyst (TIBA and DIBAH) and on the respective concentrations of these cocatalysts. As kp is not constant the authors suggest that it is better considered as an apparent rate constant ka. For the cocatalyst TIBA the dependence of ka on nA /nN< results in a S-shaped curve with a maximum in ka = 311 L mol-1 min 1 at TiBA/ Ndv = 50 while activation with DIBAH leads to an inverse u-shaped curve with a maximum ka 220 L -mol 1 min 1 at Dll Aii/ NdV = 35 (Fig. 11 in Sect. 2.2.8) [179]. 

Molar mass reduction with DIBAH was significantly more effective than with TIBA. The higher activity of DIBAH was assigned to the hydride group. The differences in the relative activities of hydride and isobutyl moieties towards substitution by living polybutadienyl chains were qualitatively described by different equilibrium positions (Scheme 33) [179,180,205]. 

Addition of triethylphosphonoacetate carbanion in THF to the 1-tetrahydro-pyranyloxycyclopropanecarboxaldehyde 171b gave the trans-vinylcyclopropane-carboxylate 219 in 88 % yield reduction of the ester with DIBAH to minimize conju-... 

Mulzer (Scheme 8 upper left) obtained the a,/(-unsaturated ester 33 with Z configuration from aldehyde 26a via a Still-Gennari olefination with phosphonate ester 34. Reduction of the ester with DIBAH and application of L-imidazole-PPhj gives allylic iodide 35. This acts as electrophile on the -anion of sulfone 36. After reductive removal of the phenylsulfone, group 28b is obtained [23]. 

Pyrrolines X -piperideines. A convenient, general synthesis of A -pyrroIincs is based on the reduction of suitable nitriles with DIBAH (equation 1). 

This rearrangement can be applied to chiral o-mesyloxy ketones by in situ reduction with DIBAH followed by addition of triethylaluminum or diethylaluminum chloride. The resulting aldehyde is reduced as formed to an optically active 2-aryl- or 2-alkenylpropanol/ Example ... 

Reduction of diynols to enynols.1 Conjugated diynols (1) are selectively reduced to (E)-enynols (2) by conversion to lithium alkynoxides with n-BuLi followed by reduction with DIBAH. 

Problem 21.19 What product would you vxpect from the Tenriiotl of butyroUcUme with DIBAH ti -TS C ... 

Aldol cyclization. Although the keto aldehyde 1 is resistant to aldol cyclization under normal, alkaline conditions, this reaction can be accomplished by a method originally developed by Raphael et Reduction of the enol lactone (2), derived from 1, with DIBAH produces a bridged ketol, which is oxidized to 3 with chromic add. This diketone was employed as an intermediate in a synthesis of the sesquiterpene gymnomitrol (4). 

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