Organoborane conversions with borabicyclo[3.3.2]decanes. Carboxylic acids via Brown's DCME and asymmetric hydroboration of 1,1'-disubstituted alkenes combined with Suzuki cross-coupling

The application of Brown's alpha,alpha-dichloromethyl methyl ether (DCME reaction) to B-alkyl-9-oxa-10-borabicyclo[3.3.2]decanes represents a convenient method for the preparation of carboxylic acids. The bicyclic OBBD borinate esters are obtained by the selective oxidation of B-substituted derivatives of 9-borabicyclo[3.3.1]nonane (9-BBN) with anhydrous trimethylamine N-oxide (TMANO).32 This reaction is highly efficient affording high yields and by using only one equivalent of this oxidizing agent, neither the R group nor a second ring B-C is oxidized. Thus, the DCME reaction will be intentionally designed to transfer just one alkyl group. Specifically, the hydroboration and subsequent oxidation of 1-octene with 9-BBN-H and TMANO, respectively, produces exclusively B-octyl-9-oxa-10-borabicyclo[3.3.2]decane in 92 % yield. The insertion of the DCME reagent (LiCCl2OMe) occurs exclusively into the B-R bond, affording the corresponding homologated nonanoic acid after the oxidative work up. Another important feature of this methodology is the advantage that by hydroborating with 9-BBN-H only one regioisomeric adduct is normally obtained. Alternatively, organolithium reagents can be used to produce the B-alkyl-9-borabicyclic[3.3.1]nonanes, which in turn can be transformed to the corresponding B-R-OBBDs. The DCME process was successfully performed providing high yields of the homologated carboxylic acids.;Chiral 10-phenyl-9-borabicyclo[3.3.2]decane (B-H-BBD) was prepared in enantiomerically pure form. Hydroboration of 1,1-disubstituted alkenes with (B-H-BBD) produces asymmetric trialkylboranes. The diastereomeric composition of these boranes was determined by 11B NMR KH analysis of the corresponding borohydride and by 13C NMR. The trialkylboranes were oxidized and the alcohol product enantio purity was determined through their conversion to the corresponding diazaphosphonates and their analysis by 31P NMR. Using this methodology ibuprofen was prepared from the hydroboration of 1-isobutyl-4-isopropenylbenzene with optically pure B-H-BBD and subsequent oxidation affording the optically active ibuprofen in 74 % ee.;These trialkylboranes form "ate" complexes with NaOH or NaOMe, and undergo efficient Suzuki coupling reactions. The stereochemistry of the alkyl group transfer occurs with complete retention of configuration with respect to carbon. This methodology presents a unique way to produce optically active hydrocarbons. The absolute configurations of some of these hydrocarbons were determined by optical rotation and comparing these with previously known optically active alkanes. The Suzuki cross-coupling reaction with these adducts produced corresponding alkanes or alkenes in good yields (50--84 %).