Crotylation substrate-directed

The enantioselective lithiation of anisolechromium tricarbonyl was used by Schmalz and Schellhaas in a route towards the natural product (+)-ptilocaulin . In situ hthi-ation and silylation of 410 with ent-h M gave ewf-411 in an optimized 91% ee (reaction carried ont at — 100°C over 10 min, see Scheme 169). A second, substrate-directed lithiation with BuLi alone, formation of the copper derivative and a quench with crotyl bromide gave 420. The planar chirality and reactivity of the chromium complex was then exploited in a nucleophilic addition of dithiane, which generated ptilocaulin precnrsor 421 (Scheme 172). The stereochemistry of componnd 421 has also been used to direct dearomatizing additions, yielding other classes of enones. ... 

Kishi and co-workers elegantly demonstrated the power of substrate-directed cro-tylation reactions in their synthesis of the C(15)-C(29) segment 83 of rifamycin S (Fig. 11-10) [61]. This synthesis utilizes two crotylation reactions with the Noza-ki-Hiyama crotylchromium reagent 8 [18, 19] and one allylation reaction using allyldichloroiodostannane [79]. 

The synthesis of 83 began with aldehyde 84 (Scheme 11-1) [61]. Substrate-directed reaction of 84 with (Zs)-crotylchromium 8, generated in situ from ( )-crotyl-iodide, occurred with >91 9 diastereoselectivity for the Felkin adduct 85. Adduct 85 was subsequently elaborated to aldehyde 86, which underwent a Felkin-selec-... 

The excellent diastereoselection of all three of these substrate-directed allylation reactions is consistent with reaction occurring through Felkin transition states analogous to 39 (Fig. 11-6). These examples illustrate the excellent stereochemical control opportunities that exist in ( )-crotylation reactions of a-methyl chiral aldehydes, especially when the -position is branched (as in the (7s)-crotylation of 25 and 32, see above). 

Triple bonds do not need to be protected for crotylation reactions. However, when the crotylation was performed with 14 to yield 15 directly, the syn/anti selectivity was only 2 1. This selectivity could be improved to >10 1 by using 25 as substrate. 

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