Iron-Catalyzed 1,4-Hydroboration of 1,3-Dienes

Iron can adopt formal oxidation states ranging from –II 1 to +VI. 2 Iron complexes are used as catalysts in synthetic chemistry for carbon–heteroatom 3 and carbon–carbon bond forming reactions. 4 Low-valent iron complexes can catalyze cross-coupling, 4 cycloisomerization, 5 and cycloaddition reactions. 6,7

Iron can adopt formal oxidation states ranging from -II 1 to +VI. 2 Iron complexes are used as catalysts in synthetic chemistry for carbon-heteroatom 3 and carbon-carbon bond forming reactions. 4ow-valent iron complexes can catalyze cross-coupling, 4 cycloisomerization, 5 and cycloaddition reactions. 6,7We are interested in iron catalysis for the identification of useful, previously inaccessible reaction chemistry and report here C-B bond formation by hydroboration of 1,3-dienes.
To our knowledge, there are no other examples of Fe-catalyzed hydroboration reactions of olefinic substrates.The allylborane products are formed regio-and stereoselectively with (E)-double bond geometry exclusively and are challenging to access selectively with conventional chemistry.
We have previously reported a 1,4-addition reaction of αolefins to dienes using an iminopyridine-ferrous chloride 8 complex with magnesium metal as an in situ reducing agent. 9In this Communication, we describe the use of analogous, readily prepared iminopyridine-derived iron complexes as catalysts for the regioselective 1,4-addition of pinacolborane (HBPin) to substituted 1,3-dienes (eq 1).
Allylboranes are versatile intermediates employed in oxidation to allylic alcohols, 10 allylation to give homoallylic alcohols 11 and amines, 12 and Suzuki cross-coupling reactions. 13Traditional methods to synthesize allylboranes involve basic main group organometallics, such as Grignard and organolithium reagents, that are incompatible with electrophilic functional groups.11a While transition-metal-catalyzed hydroboration of olefins has been studied extensively with great success, 14 hydroboration of dienes to access allylboranes is less established.Palladium(0) catalyzes the 1,4-addition of catecholborane to unfunctionalized 1,3-dienes such as 1,3-pentadiene and isoprene to give (Z)branched allylboranes, 15 and Ni II - 16 and Rh I -catalyzed 17 reactions are selective for 1,2-addition.
The synthesis of linear (E)-γ-disubstituted allylboranes is attractive because, for example, they can afford trisubstituted allylic alcohols stereospecifically and add to electrophiles to generate quaternary stereocenters with control of diastereoselectivity. Challenges in the synthesis of linear (E)-γdisubstituted allylboranes via hydroboration of 1,3-dienes include control of chemoselectivity to favor 1,4-over 1,2-addition, control of regioselectivity to favor C-B bond formation at a single diene terminus, and control of stereoselectivity to favor E-olefin geometry.The hydroboration reaction presented herein controls all three types of selectivity.A general method to synthesize linear (E)-γ-disubstituted allylboranes has not been reported previously. 18e observed that hydroboration of myrcene (1) to geranylpinacolborane (2a) was catalyzed by the iminopyridineiron(II) complex 3•FeCl 2 , upon addition of magnesium metal, after 3 h at 23 °C in 80% yield (eq 1).The combination of ligand, ferrous chloride, and magnesium was necessary for catalysis.Pinacolborane generally afforded allylboranes that were stable to air, water, and chromatography on silica gel; other borolanes, such as those derived from catecholborane, were not stable towards hydrolysis or chromatography on silica gel.
Evaluation of different bidentate ligands (see Supporting Information) showed that iminopyridine ligands gave the highest yields for hydroboration.The redox activity of iminopyridine ligands may play a role in effecting efficient catalysis. 20Ligand optimization revealed that variation of the substituent of the imine nitrogen modulates the 1,4-regioselectivity to favor either the branched or the linear isomer (eqs 1 and 2).1,4-Addition of pinacolborane to myrcene (1) catalyzed by 3•FeCl 2 produced geranylpinacolborane (2a) in 93:7 (2a:2b) regioselectivity and >99:1 E/Z selectivity in 89% overall yield (eq 1).When catalyst 4•FeCl 2 was used, the regioselectivity inverted to afford branched allylborane 2b as the major product in 78% isolated yield (92% yield of combined regioisomers, eq 2).The ligand-controlled regioselectivity is of synthetic value and may be set during migratory insertion (see mechanistic hypothesis, Scheme 1).
The Fe-catalyzed hydroboration can be performed in the presence of electrophilic functionality, such as the ester in 19, that is incompatible with the basic conditions of traditional allylborane syntheses.11a Notably, hydroboration is chemoselective, and 1,4-addition to 1,3-dienes proceeds without hydroboration of isolated olefins such as in 21.We attribute the high chemoselectivity of diene versus olefin hydroboration to the affinity of 1,3-dienes for low-valent iron. 24The Fecatalyzed hydroboration of all dienes investigated is selective for 1,4-addition to produce allylboranes stereo-and regioselectively.1,2-Addition products could not be detected by 1 H NMR. The major regioisomers 12a-22a were formed with (E)-double bond geometry exclusively, consistent with the proposed mechanism in Scheme 1. Products with trisubstituted double bonds can otherwise be challenging to synthesize stereoselectively, especially when the substituents are similar in size. 25llylic alcohols with trisubstituted double bonds are substrates for asymmetric catalytic reactions, such as Noyori hydrogenation, 26 isomerization to generate chiral aldehydes, 27 and Sharpless asymmetric epoxidation. 28All reactions require the alcohol substrate to be stereochemically pure with respect to double bond geometry to attain high levels of enantioselectivity.The presented Fe-catalyzed hydroboration provides ready access to allylic alcohols with (E)-trisubstituted double bonds in high stereoselectivity (> 99:1, eqs 3 and 4). 25 For example, allylic alcohol 23 was synthesized in two steps by hydroboration of (+)-nopadiene (15) The Fe-catalyzed reaction can also be used in a one-pot hydroboration-allylation reaction, as shown in eq 5. Benzaldehyde was added, subsequent to 1,4-hydroboration of ester 19, to give a 93:7 mixture of homoallylic alcohols 25a and 25b resulting from the two regioisomers 20a and 20b.Homoallylic alcohol 25a was formed as a single diastereomer, as determined by 1 H NMR spectroscopy.Lactone formation afforded 26 in 85% yield as a single diastereomer.Alcohol 25a and δ-lactone 26 both contain an all-carbon quaternary center; the relative stereochemistry in 25a and 26 is a result of the E-configuration of the γ-disubstituted allylborane generated in the Fe-catalyzed hydroboration.(5) A preliminary mechanistic analysis led us to propose the catalytic cycle shown in Scheme 1.The deuterium atom from pinacolborane-d was found at the methyl group of the hydroborated product 2a-d exclusively.Selective deuteration is consistent with migratory insertion into either the Fe-B or the Fe-H bond via the iron allyl intermediates 29a and 29b, respectively but cannot distinguish between the two pathways.Proposed compounds 29a and 29b were not observed during catalysis.The turnover-limiting step and the reversibility of the steps of the catalytic cycle are currently unknown and, hence, the ligand-controlled regioselectivity (e.g.entries 6 vs. 7) could be determined during oxidative addition or migratory insertion.When the branched isomer 2b was subjected to the reaction conditions of hydroboration, no linear isomer 2a was observed, which established that at least one step after the regioselectivitydetermining step is irreversible.The selectivity for double bond geometry can be rationalized by the proposed mechanism due to syn migratory insertion to Fe-allyl 29a or 29b.In conclusion, we report a chemo-, regio-, and stereoselective Fe-catalyzed hydroboration of 1,3-dienes to afford linear (E)-γdisubstituted allylboranes.
The iminopyridine-Fe-catalyzed reaction provides access to allylboranes-versatile building blocks-that are challenging to prepare by traditional allylborane syntheses or other known transition metal-catalyzed reactions.The hydroboration reaction demonstrates previously unknown reactivity for iron.