Borohydride-Mediated Radical Addition Reactions of Organic Iodides to Electron-Deficient Alkenes

Abstract

Cyanoborohydrides are efficient reagents in the reductive addition reactions of alkyl iodides and electron-deficient olefins. In contrast to using tin reagents, the reaction took place chemoselectively at the carbon-iodine bond but not at the carbon-bromine or carbon-chlorine bond. The reaction system was successfully applied to three-component reactions, including radical carbonylation. The rate constant for the hydrogen abstraction of a primary alkyl radical from tetrabutylammonium cyanoborohydride was estimated to be <1 × 10(4) M(-1) s(-1) at 25 °C by a kinetic competition method. This value is 3 orders of magnitude smaller than that of tributyltin hydride.

A New Mode of Chemical Reactivity for Metal‐Free Hydrogen Activation by Lewis Acidic Boranes

“…Both boranes have essentially identical steric shielding of the central boron atom by the six ortho methyl groups on the mesityl rings,l eading to the formation of long-lived borane radical anions upon reduction. [9,10] Neither borane is currently known to be active for H 2 activation within an FLP.T he addition of six electronwithdrawing nitro groups in 1 shifts the reduction potential in ap ositive direction to À1.57 Vv s. Cp 2 Fe 0/+ (see the Supporting Information), making 1 as electrophilic and comparably facile to reduce as the archetypal electrondeficient borane B(C 6 F 5 ) 3 used in FLP chemistry (À1.52 V vs.Cp 2 Fe 0/+ ), [7b,e-g] and much easier to reduce than 2 (approximately À2.8 Vv s. Cp 2 Fe 0/+ ). [11] TheN O 2 groups in 1 also provide useful electron paramagnetic resonance spectroscopic markers for the characterization of reaction intermediates.…”

“…Thevery negative redox potential of 2 necessitates the use of astronger reducing agent. When asolution of 2 in [D 8 ]THF is reduced over sodium metal [10] and heated in the presence of H 2 the appearance of ad oublet in the 11 BNMR spectrum at d = À14.5 ppm ( 1 J B,H = 78 Hz), and ac orresponding 1:1:1:1 quartet in the 1 HNMR spectrum at d = 3.75 ppm ( 1 J H,B = 77 Hz) is observed, characteristic of the formation of [Na]- [2-H] (Figure 1b). Theexperiments described above clearly indicate that the borane radical anions 1C À and 2C À can cleave H 2 in the absence of any exogenous Lewis base.T hese reactions are,h owever, slow in comparison to typical FLP H 2 activation reactions.In the case of the model borane 1,t his is advantageous,s ince it enables the reaction to be monitored in real time and reaction intermediates along the H 2 cleavage pathway to be observed using EPR spectroscopy.…”

Synthesis of α‐Chlorolactams by Cyanoborohydride‐Mediated Radical Cyclization of Trichloroacetamides

“…The efficiency of the cyclization ending with a primary alkyl radical in these reaction conditions ( II → III ) is notable, since Ryu showed by theoretical calculations that the hydrogen‐transfer between alkyl radicals and NaBH 3 CN was slower than that observed with radicals bearing an electron‐withdrawing group, which are formed in cyanoborohydride‐mediated Giese‐type reactions . Additionally, it cannot be ruled out that the mechanism of the chlorine‐atom transfer may be an electron‐transfer process between BH 2 CN .− (expected to be a strong reducing agent) and trichloroacetamide , …”

Total synthesis of proposed cephalosporolides H and I

“…CuClcatalyzed cross-coupling of 15 and 10 furnished 1b in 86% yield, further affirming the S configuration at C-6 of 14. Conveniently, a NaBH 3 CN/AIBN promoted radical Michael addition 23 between 15 and benzyl acrylate furnished the corresponding benzyl ester 16, which was converted into (S)-cephalosporolide I (2b) with H 2 in the presence of 10% Pd/C in MeOH.…”