P. Roy and Diana T. Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, USA.
J Am Chem Soc. 2010 Jan 13;132(1):402-12. doi: 10.1021/ja907781t.
Highly enantio- and diastereoselective methods for the synthesis of a variety of cyclopropyl alcohols are reported. These methods represent the first one-pot approaches to syn-vinyl cyclopropyl alcohols, syn-cis-disubstituted cyclopropyl alcohols, and anti-cyclopropyl alcohols from achiral precursors. The methods begin with enantioselective C-C bond formations promoted by a MIB-based zinc catalyst to generate allylic alkoxide intermediates. The intermediates are then subjected to in situ alkoxide-directed cyclopropanation to provide cyclopropyl alcohols. In the synthesis of vinyl cyclopropyl alcohols, hydroboration of enynes is followed by transmetalation of the resulting dienylborane to zinc to provide dienylzinc reagents. Enantioselective addition to aldehydes generates the requisite dienyl zinc alkoxides, which are then subjected to in situ cyclopropanation to furnish vinyl cyclopropyl alcohols. Cyclopropanation occurs at the double bond allylic to the alkoxide. Using this method, syn-vinylcyclopropyl alcohols are obtained in 65-85% yield, 76-93% ee, and > 19:1 dr. To prepare anti-cyclopropanols, enantioselective addition of alkylzinc reagents to conjugated enals provides allylic zinc alkoxides. Because direct cyclopropanation provides syn-cyclopropyl alcohols, the intermediate allylic alkoxides were treated with TMSCl/Et(3)N to generate intermediate silyl ethers. In situ cyclopropanation of the allylic silyl ether resulted in cyclopropanation to form the anti-cyclopropyl silyl ether. Workup with TBAF affords the anti-cyclopropyl alcohols in one pot in 60-82% yield, 89-99% ee, and > or = 10:1 dr. For the synthesis of cis-disubstituted cyclopropyl alcohols, in situ generated (Z)-vinyl zinc reagents were employed in asymmetric addition to aldehydes to generate (Z)-allylic zinc alkoxides. In situ cyclopropanation provides syn-cis-disubstituted cyclopropyl alcohols in 42-70% yield, 88-97% ee, and > 19:1 dr. These one-pot procedures enable the synthesis of a diverse array of cyclopropyl alcohol building blocks with high enantio- and diastereoselectivities.
报道了多种环丙醇的高对映选择性和非对映选择性合成方法。这些方法代表了首例从非手性前体制备顺式-乙烯基环丙醇、顺式-二取代环丙醇和反式环丙醇的一锅法。这些方法以基于 MIB 的锌催化剂促进的对映选择性 C-C 键合反应为起点，生成烯丙基醇盐中间体。然后，中间体进行原位醇盐导向的环丙烷化反应，得到环丙醇。在乙烯基环丙醇的合成中，对炔进行硼氢化反应，然后将生成的二烯基硼烷经转金属化转化为锌，得到二烯基锌试剂。醛的对映选择性加成生成所需的烯丙基锌醇盐，然后进行原位环丙烷化反应，得到乙烯基环丙醇。环丙烷化发生在醇盐的烯丙位。使用该方法，顺式-乙烯基环丙醇以 65-85%的收率、76-93%的对映体过量和>19:1 的 dr 得到。为了制备反式环丙醇，通过手性锌试剂与共轭烯醛的对映选择性加成得到烯丙基锌醇盐。由于直接环丙烷化生成顺式环丙醇，因此将中间的烯丙基醇盐用 TMSCl/Et(3)N 处理，生成中间的硅醚。原位环丙烷化烯丙基硅醚生成反式环丙基硅醚。用 TBAF 处理后一锅法得到反式环丙醇，收率 60-82%，对映体过量 89-99%，dr 值>或=10:1。对于顺式二取代环丙醇的合成，在不对称加成醛中使用原位生成的（Z）-乙烯基锌试剂生成（Z）-烯丙基锌醇盐。原位环丙烷化提供顺式-顺式二取代环丙醇，收率 42-70%，对映体过量 88-97%，dr 值>19:1。这些一锅法能够以高对映选择性和非对映选择性合成多种环丙醇砌块。
