Z-tamoxifen

Diorganozincs add to substituted phenylacetylenes with high regioselectivity and complete stereoselectivity (syn-addition).35 This methodology has been recently used to prepare the anti-cancer drug (Z)-Tamoxifen (Scheme 10.13).35... 

Z-tamoxifen 403 tandem cyclization 290, 295 tandem Heck reaction-anion capture 253-4 tandem Heck reaction-phenoxide capture 253 tandem Heck reactions 251, 252-4 tandem intramolecular Heck-intermolecular Stille cross-coupling 255 taxol 140, 143,243,245 ( )-tazettine 146,234 telomerization 352 telomerization products 343, 345 template effect 140 teraconic anhydride 468 terminal acetylenes, synthesis of 216-20 terminal alkynes 6, 213 terminal 2,2-diorgano-l-aIkcnylboronates 51 terminal diynes 207 ternary complex 444 ternary coupling 177... 

Remarkably, this carbozincation procedure works well at low temperature and even allows an efficient addition of the relatively unreactive Me2Zn. It was soon found that diarylzincs undergo the addition even more readily, and this reaction has been used to prepare Z-tamoxifen 46, which is a commercial antitumor drug (Scheme 9-40) [78]. 

Rigorous comparisons of metal countercations are still relatively rare. In the synthesis of (Z)-tamoxifen and related compounds, Mg and Zn appear to be superior to Sn in terms of stereospecificity and operational simplicityt (Scheme 40). In cases where chemoselectivity is critically important, as in the synthesis shown in Scheme Zn would have to be chosen over Mg. 

Scheme 3.36 Synthesis of (Z)-tamoxifen by Pd-catalyzed Negishi or Suzuki cross-coupling [151, 152].

Scheme 10.82 Carbolithiation of diphenylacetylene application to the synthesis of the estrogen-dependent breast cancer therapeutic agent (Z)-tamoxifen [65].

This carborane cage has also been used to prepare complex 19 which, with its dimethylamino chain, identical to that of hydroxytamoxifen, acts as an efficient antiestrogen [68], while complex 20, based on the structure of (Z)-tamoxifen [70] and thus without an O H group, has no affinity whatsoever for the estradiol receptor [71]. 

Taniguchi N. Copper-catalyzed synthesis of p-haloalkenyl chalcogenides hy addition of dichalcogenides to internal alkynes and its application to synthesis of (Z)-tamoxifen. Tetrahedron 2009 65 2782 2790. 

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