Keck conditions

The Keck macroiactonization was used by R.J.K. Taylor et al. to close the 10-membered ring of (+)-apicularen A. The lactonization was attempted using both the Yamaguchi and Mitsunobu procedures and neither gave even a trace of the cyclic product. However, when the Keck conditions were applied, the desired lactone was isolated in moderate yield. 

Under 1 arcsec seeing, the LGS FWHM was 1.4 arcsec. Images taken with the Keck primary mirror defocused (Fig. 24) demonstrated the level of distortion expected for an off-axis projection system. Low-level scattering was also minimal, consistent with expectations and seeing conditions. 

Muller MB, Keck ME (2002) Genetically engineered mice for studies of stress-related clinical conditions. J Psychiatr Res 36 53-76... 

Several controlled trials have shown that lithium is efficacious in the maintenance treatment of bipolar disorder, with higher serum levels (0.8 1 mol/1) being more indicative of successful prophylaxis (Keck and McElroy. 2002). Valproic acid also appears to have efficacy in maintenance therapy, specifically in bipolar patients with mixed mania and rapid cycling (Bowden et al., 1995). The results concerning carbamazepine s efficacy as a maintenance medication are controversial (Stuppaeck et al., 1994). Other potential agents with some evidence of good maintenance value include clozapine and olanzapine. A combination of lithium and carbamazepine or other anticonvulsants is recommended under certain conditions if an adequate preventive effect cannot be obtained with the substances individually (Bauer et al., 2002). 

Interestingly, reduction of tert-butyl ketone 13 under the same conditions gave 1,3-diol 14 as a 1 1 mixture of diastereoisomers. Keck argued that samarium and its associated ligands are similar in size to the tert-butyl group and there is no preference for one organosamarium configuration over the other (Scheme 4.8).13... 

Keck showed that protection of the (1-hydroxyl group in (5-hydroxy ketones as tert-butyldimethylsilyl and benzyl ethers shut off reduction and starting material was recovered. This underlines the importance of pre-coordination of Sm(II) to the free hydroxyl in the directed reduction.13 The mm -selective reduction does, however, tolerate methyl, MOM, MTM and MEM ethers, presumably as these small ether groups still allow coordination to Sm(II).14 Keck pointed out that care should be taken when working with different systems as selectivities can be very substrate dependent.13 Flowers has also shown that the diastereoselectivity of the reduction can be altered by changing the reaction conditions through the use of other solvents or reaction protocols.15,16... 

Bromo-acetal 151 was subjected to tributyltin hydride promoted radical cyclization and afforded a stereoselective 8-C-methyl derivative 152. (O Scheme 40) Similarly, treatment of 151 under Keck s conditions [62] with allyltributyltin and AIBN resulted in the formation of a bis-C,C-glycoside 153 [63]. 

A convergent, stereocontrolled total synthesis of the microtubule-stabilizing macrolides, epothilones A and B was achieved in the iaboratory of S.J. Danishefsky. During their investigations, they examined several approaches to construct these natural products. One possible strategy to introduce the Cl 5-hydroxyl group in an enantioselective fashion was to use Keck s asymmetric allylation method. Under standard conditions, the reaction provided the desired homoallylic alcohol in good yield and excellent enantioselectivity. 

The spongistatins are a family of architecturally complex bisspiroketal macrolides, which display extraordinary cytotoxicity. During the second generation synthesis of the ABCD subunit of spongistatin 1, A.B. Smith and coworkers utilized the Keck allylation to construct the Kishi epoxide. The allylation was carried out under standard conditions, using tributyl-(2-ethylallyl)-stannane as the allylstannane reactant. The desired product was formed in high yield and a diastereomeric ratio greater than 10 1. 

The total synthesis of a novel fungicidal natural product, (-)-hectochlorin, was accomplished by J.R.P. Cetusic and co-workers. The final step in their synthetic route was the Keck macrolactonization under the original conditions developed by Keck et al. The substrate hydroxy acid was dissolved in ethanol-free CHCI3 and was slowly added to a chloroform solution of DCC, DMAP and DMAP-HCI at reflux temperature. 

Manzamine A is an alkaloid that was shown to inhibit the growth of P-388 mouse leukemia cells. The synthesis of the tetracyclic substructure of this natural product was reported by D.J. Hart. For the construction of the perhydroisoquinoline moiety, he utilized the Keck radical allylation. This transformation was carried out under standard conditions, reacting a secondary alkyl iodide with allyltributyltin. 

Keck and co-workers have investigated the exo cyclizations of the allylstan-nanes (Z)-158 and ( )-159 these reactions can be promoted by both thermal and Lewis acidic conditions (Table 11-10) [54]. As illustrated in Table 11-10, the (Z)-stannane 158 preferentially forms the 1,2-syn adduct 160 under both thermal promotion and catalysis by Bp3 OEt2. In contrast, the (i )-stannane 159 cyclizes to form the, 2-anti carbocycle 161 as the major adduct in the BF -OEta-catalyzed allylation, while the, 2-syn carbocycle 160 is the major adduct in the thennji] allylation process. 

Yamamoto found that, in general, the (Z)-stannanes 170 favored formation of the syn adducts 173 under thermal conditions, presumably through transition state 174 (Fig. 11-16). Under thermal conditions, however, the (F)-stannanes 171 generally favor formation of the anti adducts 172, where the anti stereochemistry is rationalized by reaction occurring through transition state 175. Also different from Keck s observations, Yamamoto found that the anri-adducts 172 were formed preferentially (via transition state 176) in the Lewis acid-promoted reactions of both the (Z)-170 and the ( )-171 substrates. Thus, as noted by Yamamoto, the secondary orbital interactions or the dipole effects experienced in the ring-closing transition states with the (y-alkoxyallyl)stannanes 170 and 171 are apparently not as important in the reactions of 158 and 159 [106]. 

Using Keck s original catalytic allylation procedure, Danishefsky and co-workers converted aldehyde 474 to the homoallylic alcohol 475 (conditions A, Scheme 11-38, 60% yield, >95% ee) used in their total synthesis of epothilones A and B [314], Asymmetric allylation with a stoichiometric amount of Brown s reagent, [(-)-lpc]2BAll (195), however, was higher yielding and required a shorter reaction time (conditions B, Scheme 11-38, 83% yield, >95% ee). 

Keck has also described a mechanistic study of the intra-molecular allylations of Z-16 and -19 under a variety of conditions.These results are summarized in Scheme 5.2.4, as the Z-16 consistently gave the major product 18 upon treatment with Brpnsted and Lewis acids. The observed stereoselectivity is rationalized through the synclinal arrangement 17. 

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