Communication pubs.acs.org/JACS
Nickel-Catalyzed Direct Synthesis of Aryl Olefins from Ketones and Organoboron Reagents under Neutral Conditions Chuanhu Lei, Yong Jie Yip, and Jianrong Steve Zhou* Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, SPMS-CBC-06-03, Singapore 637371, Singapore S Supporting Information *
ABSTRACT: Nickel-catalyzed addition of arylboron reagents to ketones results in aryl olefins directly. The neutral condition allows acidic protons of alcohols, phenols, and malonates to be present, and fragile structures are also tolerated.
A
ryl olefins are useful in the synthesis of bioactive compounds and drugs.1 They are present as structural motifs in drugs including isocombretastatin A, tamoxifen, bexarotene, and ratanhine. Diarylethenes are also present in photoresponsive molecular switches, motors, and medicines.2 Among many methods to access these olefins,3 common ones include Wittig methylenation of ketones and addition of aryl Grignard reagents, followed by acidic dehydration or basic elimination after activation of alcohols.4 Unfortunately, the basic reagents and acidic conditions are incompatible with sensitive groups and acidic protons when they are present in target compounds. Previously, we and other groups reported Heck arylation of cyclic olefins to produce 1-aryl olefins.5 We also disclosed αselective Heck arylation of terminal aliphatic olefins and aryl olefins.6 However, the Heck procedures are limited to simple terminal olefins and cyclic olefins. Cross-coupling reactions7 of alkenyl electrophiles or alkenylmetals, another common approach, have poor atom economy, and the reagents need to be prepared beforehand. Notably, cross-coupling of elaborate alkenyl triflates, derived from ketones, is often employed in synthesis of complex bioactive compounds.8 Barluenga arylation of N-tosylhydrazones, also prepared from ketones, allows quick access to aryl cycloolefins or 1,1-diarylalkenes.9 The use of strong bases, however, is incompatible with sensitive groups, and poor E/Z ratio of olefinic isomers was seen in some products.10 Herein, we report a general arylation to form 1-aryl olefins from various ketones under neutral conditions. Recently, we found serendipitously that a nickel-catalyzed reaction between acetophenone and phenylboroxine afforded 1,1-diphenylethylene in good yield (Figure 1) when the Ni(0) catalyst of 1,2-bis(dicyclohexylphosphino)ethane (dcype) was used. Other common diphosphines, e.g., binap, dppe, dppp, dppb, and dppf, and monophosphines such as PPh3, PCy3, PtBu3, Davephos, and XPhos, afforded very little product (90% yield within 1 h after passing an aliquot of the reaction mixture through silica gel. D then slowly converted to 1,1-diphenylethene in >90% yield over 24 h. (b) TEMPO inhibited the Ni catalysis, but no trapped radical species was detected. (c) A trace amount of water dramatically accelerated the formation of D in the initial phase of the reaction
Figure 2. Arylation of ketone using phenylboroxine (yields in parentheses were obtained with 1 equiv of phenylboroxine).
the same result (Figure 2d). However, Ni salts failed to efficiently catalyze the aryl olefin formation in good yields, even in the presence of zinc powder. Arylboroxines of diverse electronic properties efficiently added to acetophenone (Figure 3a). In general, electron-deficient aryl rings led to relatively low yields of aryl olefins (3k,aw). Adding a panisyl ring to a substituted acetophenone provided 3az, a structural analogue of an antitumor agent, isocombretastatin A (Figure 6087
DOI: 10.1021/jacs.7b02742 J. Am. Chem. Soc. 2017, 139, 6086−6089
Communication
Journal of the American Chemical Society
Figure 6. Arylation of two methyl ketones, 1,4-dione and α,β-enone.
Figure 5. Mechanistic studies and a proposed catalytic cycle.
but had little influence on carbinol elimination (for details, see the Supporting Information (SI)). To determine conditions necessary for dehydration, we next subjected carbinol D to various conditions (Figure 5b). All of Ni(PPh3)4, bisphosphine dcype, and phenylboroxine were needed for dehydration, to our surprise. No olefin was formed without phenylboroxine, while
