Chiral BINOL-derived diols catalyze the enantioselective asymmetric allylboration of acyl imines. The reaction requires 15 mol% of (S)-3,3′-Ph 2 -BINOL as the catalyst and allyldiisopropoxyborane as the nucleophile. The reaction products are obtained in good yields (75 -94%) and high enantiomeric ratios (95:5 -99.5:0.5) for aromatic and aliphatic imines. High diastereoselectivities (dr > 98:2) and enantioselectivities (er > 98:2) are obtained in the reactions of acyl imines with crotyldiisopropoxyboranes. This asymmetric transformation is directly applied to the synthesis of maraviroc, the selective CCR5 antagonist with potent activity against HIV-1 infection. Mechanistic investigations of the allylboration reaction including IR, NMR, and mass spectrometry study indicate that acyclic boronates are activated by chiral diols via exchange of one of the boronate alkoxy groups with activation of the acyl imine via hydrogen bonding.

Chiral BINOL-derived diols catalyze the enantioselective asymmetric allylboration of ketones. The reaction requires 15 mol % of 3,3'-Br2-BINOL as the catalyst and allyldiisopropoxyborane as the nucleophile. The reaction products are obtained in good yields (76-93%) and high enantiomeric ratios (95:5-99.5:0.5). High diastereoselectivities (dr >/= 98:2) and enantioselectivities (er >/= 98:2) are obtained in the reactions of acetophenone with crotyldiisopropoxyboranes.

Alkyl–B(C6F5)2 boranes are markedly α-CH-acidic. Using DFT we have calculated the pK a-values of a series of examples. Typically, (C6F5)2B–CH3 [pK a (calcd) = 18.3 in DMSO, 16.2 in dichloromethane] is almost as CH-acidic as cyclopentadiene.

Chiral α,β-dihydroxy carboxylic acids catalyze the enantioselective addition of alkenyl-and aryl boronates to chromene acetals. The optimal carboxylic acid is a tartaric acid amide, easily synthesized via a 3-step procedure. The reaction is enhanced by the addition of Lanthanide triflate salts such as cerium(IV)-and ytterbium(III) triflate. The chiral Brønsted acid and metal Lewis acid may be used in as low as 5 mol % relative to acetal substrate. Optimization of the reaction conditions can lead to yields >70% and enantiomeric ratios as high as 99:1. Spectroscopic and kinetic mechanistic studies demonstrate an exchange process leading to a reactive dioxoborolane intermediate leading to enantioselective addition to the pyrylium generated from the chromene acetal.Boronates exhibit wide-ranging utility in synthesis. [1] As carbon donors in cross coupling reactions [2] and metal-based nucleophiles in π addition reactions, [3] their utility is characterized by their ease of preparation, stability towards isolation and storage, and predictable reactivity patterns to afford valuable products. [4] In a seminal discovery Petasis demonstrated how boronates could be activated towards addition to iminiums. [5] However, an elusive area of reactivity is the addition of vinyl and aryl boronates to carbonyls and oxoniums.[6] While less reactive than imines and iminiums, carbonyl-based electrophiles would significantly expand the utility of boronates in synthesis. Coincident with our interest in new reaction methodology [7] we sought to expand the repertoire of nucleophilic boronate reactions to enantioselective addition to acetals.[8] We identified 2-alkoxy-2H-chromenes as our first substrate class for investigation [Eq. (1) The addition of vinyl and aryl based nucleophiles to this class of electrophiles give rise to chiral chromene products [10] that could readily be utilized in the synthesis of benzopyran containing natural products (Figure 1) We initiated our study by investigating the addition of boronate 5 to 2-ethoxy-2H-chromene 4 (Table 1). A brief survey of Lewis acids failed, providing none of the desired addition product when used in catalytic amount and led to substantial decomposition of the chromene 4. We postulated that organic acids would serve as mild catalysts for the formation of the pyrylium, thereby promoting the reaction. Indeed, the use of acetic acid and trifluoroacetic acid provided the desired addition product 6 in modest yields ( Encouraged by these preliminary results, we explored the use of available chiral acids. (+)-Mandelic acid 9 and dihydroxy acid 10 were nominally successful at promoting the enantioselective addition reaction (entries 3 & 4). However, the use of catalytic N-Boc amino acids derived from L-serine and L-threonine resulted in a more selective reaction. Notably, L-threonine 12 afforded the product in lower selectivity than L-serine 11 (entries 5 & 6); enantioselectivity that returned upon use of the epimeric allo-L-threonine (entry 7). Theses results led us to consider ...