MNDO Analysis of Regio‐ and Stereoselectivity in Hydroboration

Abstract

The origin of regioselectivity in hydroboration of olefins has been analyzed by MNDO methodology. With a standard transition structure derived from full MNDO optimizations, a linear correlation between calculated and experimental regioselectivities has been found. A similar approach applied to asymmetric inductions of hydroboration with chiral hydroborating agents lead also to an acceptable linear correlation between calculated and experimental results. The MNDO method has been used for a search of alternative hydroborating agents.The observation by H. C. Brown that hydroboration of symmetrical olefins with chiral mono-and dialkylboranes followed by oxidation yields optically active alcohols has gained increasing attention [l] [2]. Due to the high enantiomeric purity which can be achieved by optimization of reaction conditions, asymmetric syntheses of natural products and other chiral compounds with hydroboration as the key step are no longer unusual [3] [4]. Apart from the remarkable results by Musamune, asymmetric hydroboration often makes use of alkylboranes which are derived from (+)-a-pinene [5]. In continuation of our experimental and theoretical studies, we have analyzed the factors which may control selectivity in hydroboration with the aim to design new reagents with high asymmetric induction [6].According to the mechanistic investigations by H . C. Brown, an olefin reacts in the rate-determining step with BH, which is formed by dissociation of a BH,.Me,S or BH,.THF complex prior to reaction with the olefin [7]. As a first approximation, solvent effects on the addition can, therefore, be ignored, and computer calculations for the gas phase can be used for the reaction in solution. Expensive optimizations of geometry parameters of solvent molecules, which are only approximately known, can thus be avoided [8]. In most cases, hydroboration of di-or trisubstituted olefins is performed in a temperature range in which the primarily formed addition products do not isomerize to the more stable alkylboranes, where the B-atom is located at a terminal C-atom [9]. Based on ab-initio calculations by Lipscomb [lo], Schleyer [ll], and Nugase [12], the structural features of the reaction of ethylene with BH, can be described in detail: The addition occurs by a z-complex and leads via a four-centre transition state to the products in a highly exothermic reaction.White showed that stereoselective hydroboration of sterically hindered cyclohexenes can be reproduced rather well by calculations based on a special force field [13]. Asymmetric hydroboration of alkenes and olefins with chral substituents has been studied by Houk [ 141. Using a combination of MM2-force-field and ab-initio calculations, the enantio-and diastereoselectivity could be well described by transition structures. The force-field methods used by White and Houk allow very fast computations, even on a

Hydroboration. 92. Investigation of Practical Methods for the Synthesis of Optically Pure Isopinocampheylchloroborane for the Asymmetric Hydroboration of Representative Prochiral Alkenes

“…These results indicate that the effectiveness of these two complimentary reagents depends on their steric requirements. This is also supported by literature reports, based on theoretical calculations, suggesting that the steric bulk and environment around the boron atom in the pinene-based borane reagents are critical for achieving a high degree of stereoselection in asymmetric hydroboration. This has been very well illustrated by the application of the sterically bulkier chiral auxiliaries, readily derived from easily accessible α-pinene, namely 2-ethyl-, 2- n -propyl-, and 2-isopropylapopinenes in asymmetric reduction and hydroboration reactions.…”

Chiral Synthesis via Organoboranes. 48. Efficient Synthesis of Trans-Fused Bicyclic and Cyclic Ketones and Secondary Alcohols in High Optical Purities via Asymmetric Cyclic Hydroboration with Isopinocampheylchloroborane Etherate

“…This unsatisfactory result led us to examine modification of the IpcBH 2 reagent in the hope of achieving improved optical yields. Literature reports suggest that the steric and electronic environment around the boron atom in pinene-based reagents must be critical for achieving a high degree of stereoselection in asymmetric hydroboration. Accordingly, we decided to explore the effect of introducing a chlorine atom into the IpcBH 2 reagent.…”

Hydroboration. 93. Convenient Conversion of Optically Pure 2-Organylapopinenes into the (2-Organylapoisopinyl)dihaloboranes Potentially Valuable for Asymmetric Synthesis via Chiral Organoboranes

“…Over the years the accumulated results have persuaded us that the remarkable chiral effectiveness of the Ipc 2 B- structure must have its origin in the 2-methyl group of the rigid “Ipc” structure 3d. Moreover, the substituent on the boron atom of the reagent also plays an important role. 5b, As a result, we decided to undertake the synthesis of a representative number of 2-R-apopinene structures, by replacing the 2-methyl of α-pinene ( 1a , Ipc) by larger R groups, providing 2-ethyl- ( 1b , Eap), 2- n -propyl- ( 1c , Pr), 2-isobutyl- ( 1d , i -Bu), 2-phenyl- ( 1e , Pap), and 2-isopropyl- ( 1f , i -Pr) 13 apopinenes in the hope of optimizing the steric fit between the substrate and that of the reagent in their reactions. We also decided to examine the effect of varying the halogen in the corresponding BX 2 derivatives.…”