Reynolds Kelly A., Finn M. G.
Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901.
J Org Chem. 1997 Apr 18;62(8):2574-2593. doi: 10.1021/jo9610016.
The adduct 3, derived from TiCl(3)(OiPr) and (Me(2)N)(3)P=CH(2), engages in a complicated set of interactions with NaN(SiMe(3))(2) and aldehydes, resulting in the requirement to use excess amounts of both reagents for the one-pot synthesis of allenes. When TiCl(2)(OiPr)(2) is used instead, ligand substitution reactions with NaN(SiMe(3))(2) are diminished and so stepwise transformations can be accomplished without excess amounts of each reagent. The selective production of vinylphosphonium salts and byproduct titanium oxides from Ti-substituted ylides and aldehydes is proposed to arise from the presence of a chloride leaving group on the metal. Isolated vinylphosphonium compounds may be deprotonated with phenyllithium to give thermally sensitive allenic phosphoranes, which have been characterized by low temperature multinuclear NMR. The reaction of allenic phosphoranes with aldehydes affords oxaphosphetane and betaine intermediates which appear to interconvert upon warming to produce allene and phosphine oxide. Dimethylamino-substituted phosphorus components are required for high yields in both steps of the allene-forming process, presumably to boost the reactivity of the hindered Ti-substituted ylide reagents and to stabilize the allenic phosphorane unit so that it may be trapped by aldehyde. The placement of chiral groups on the phosphorus methylide or aldehyde components results in low levels of enantiomeric and diastereomeric induction, respectively, during allene formation. In two cases, the diastereomeric ratios of initially-formed oxaphosphetanes have been found to differ from the diastereomeric composition of their product allenes, offering examples of the phenomenon known as "stereochemical drift". However, oxaphosphetane/betaine formation from allenic phosphorane and aldehyde has been found to be irreversible, suggesting that an intramolecular betaine olefin isomerization is responsible for the loss of stereochemical integrity during the Wittig step.
由TiCl(3)(OiPr)和(Me(2)N)(3)P=CH(2)衍生而来的加合物3，与NaN(SiMe(3))(2)和醛发生一系列复杂的相互作用，这导致在一锅法合成丙二烯时需要使用过量的这两种试剂。当改用TiCl(2)(OiPr)(2)时，与NaN(SiMe(3))(2)的配体取代反应减少，因此可以在不使用过量每种试剂的情况下完成逐步转化。由Ti取代的叶立德和醛选择性生成乙烯基鏻盐和副产物氧化钛，这被认为是由于金属上存在氯离去基团。分离得到的乙烯基鏻化合物可用苯基锂去质子化，得到热敏感的丙二烯基膦叶立德，其已通过低温多核NMR进行了表征。丙二烯基膦叶立德与醛的反应生成恶唑磷环丁烷和甜菜碱中间体，升温时它们似乎会相互转化以生成丙二烯和氧化膦。在丙二烯形成过程的两个步骤中，高收率都需要二甲基氨基取代的磷组分，大概是为了提高受阻的Ti取代叶立德试剂的反应性，并稳定丙二烯基膦叶立德单元，以便它可以被醛捕获。在手性基团位于磷叶立德或醛组分上时，在丙二烯形成过程中分别导致低水平的对映体和非对映体诱导。在两种情况下，已发现最初形成的恶唑磷环丁烷的非对映体比例与其产物丙二烯的非对映体组成不同，提供了被称为“立体化学漂移”现象的例子。然而，已发现丙二烯基膦叶立德与醛形成恶唑磷环丁烷/甜菜碱是不可逆的，这表明分子内甜菜碱烯烃异构化是Wittig步骤中立体化学完整性丧失的原因。
