Palladium-Catalyzed trans- and cis-Carboboration of Alkynes Tethered to Chloroborane with Organozirconium Reagents:  Ligand-Dependent Complementary Stereoselectivity

Abstract

There are increasing demands for organoboronic acid derivatives in synthetic organic chemistry because they exhibit remarkable reactivities upon appropriate activation, while being stable, storable, and nonpoisonous. 1 Their applications are spreading over the pharmaceutical and material sciences in recognition of the unique properties of organoboron compounds. Therefore, development of efficient methods for the synthesis of stereodefined, functionalized organoboronic acids is highly desirable.Catalytic borylation reactions have gained much attention with respect to efficiency, selectivity, and functional group compatibility. 2,3 Recent efforts have focused on the additions of boronelement bonds across carbon-carbon multiple bonds, 4 such as diboration 5 and silaboration. 6 Our attention has been focused on the development of catalytic carboboration reactions, in which B-C and C-C bonds are formed concurrently. We have so far reported two distinctive classes of carboborations, i.e., direct 7 and transmetalative 8 carboborations. While direct carboboration involves the activation of B-C bonds of the boron reagents, transmetalative carboboration uses haloborane as the source of the boryl group, with organometallic reagents as the source of the organic group. As the first example of the latter class of carboboration, we recently established that a carbon-carbon triple bond tethered to chlorobound boron underwent nickel-catalyzed carboboration upon use of alkynylstannanes as the transmetalation reagents. 8 In contrast to our mechanism-based assumption, the carboboration proceeded with a trans-addition mode. In this paper, we report a new carboboration system utilizing organozirconium reagents with palladium catalysts. The Pd/Zr system not only allows significant expansion of the substrate scope but also brings about highly stereoselective carboboration with either stereochemical course, which critically depends on the phosphine ligands.After screening various alkenyl organometallics as the transmetalation reagents, we found that reaction of alkenylzirconium reagent 2a with chloroborane 1a, which was tethered to an arylsubstituted alkyne, gave the carboboration product trans-3aa in good yield in the presence of nickel catalysts (Scheme 1). The Ni/Zr system still gave a trans-addition product with high selectivity, as did the Ni/Sn system. However, no carboboration products were obtained in the reaction of terminal or alkyl-substituted alkynes 1b or 1c, even with the Ni/Zr system.We then reexamined the transition metal catalysts for use with the organozirconium reagent. We found that palladium catalysts exhibited high catalytic activity. On using bulky trialkylphosphines such as P t Bu 3 or PCy 3 with palladium complexes such as PdCp-(allyl) or Pd(acac) 2 , the alkenylboration proceeded with high stereoselectivities for the trans-addition product, as observed in the Ni-catalyzed reaction (Table 1, entries 1 and 2). 9 To our surprise, however, the stereochemical course was completely switched to favor cis-addition, whe...

Haloboration of Internal Alkynes with Boronium and Borenium Cations as a Route to Tetrasubstituted Alkenes

“…Under these nonoptimized conditions, the second cross‐coupling step proceeded efficiently, although a minor quantity of a second isomer was produced. The two readily separable isomers of (Ph)(4‐FC 6 H 4 )CC(Ph)(4‐MeC 6 H 4 ) were produced in a 6:1 ratio, presumably the steric demand of P t Bu 3 induced cis – trans isomerization during cross‐coupling, as previously reported 9b,c…”

New Methods in Organic Synthesis Through Copper-Catalyzed Borylation Reactions: Stereoselective Synthesis of 1,4-Diols and Vinylboronates

“…To the best of our knowledge, there is only one example, described by Suginome, 33 which involves the use of a homopropargylic or propargylic alcohols derivative, a palladium catalyst, and a methylzirconium reagent (Scheme 9, equation 3). 33 We reasoned that a copper-boryl complex might be used to synthesize cis-branched methylated vinylboronates. Our idea was supported by previous reports of a coppercatalyzed hydroboration of alkynes.…”

Catalytic carboborations

“…18). 40 Aryl‐ and alkylzirconium compounds, however, did not afford carboboration products. Switching the catalyst to palladium‐phosphine catalyst significantly expand the scope of the reaction (Fig.…”