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

Abstract

Highly stereo- and enantioselective annelation has been achieved for the synthesis of trans-fused bicyclic and cyclic ketones via the asymmetric cyclic hydroboration of suitable cyclic dienes, such as 1-allyl-1-cycloalkenes or 1-vinyl-1-cycloalkenes and appropriate acyclic 1,4-dienes, respectively, with enantiomerically pure isopinocampheylchloroborane etherate (IpcBHCl·Et2O). The IpcBHCl·Et2O (an 86−90% equilibrium mixture) was readily synthesized by the reaction of an equivalent amount of hydrochloric acid in ethyl ether (Et2O) with optically pure isopinocampheylborane (IpcBH2). The hydroboration of the terminal double bond of a representative diene with IpcBHCl·Et2O readily provided the corresponding isopinocampheylalkylchloroborane (IpcRBCl). Subsequent hydridation of the IpcRBCl with lithium aluminum hydride (LAH, 0.25 equiv) at −20 or −25 °C generated the intermediate isopinocampheylalkylborane (IpcRBH) almost instantly, which then underwent a rapid stereospecific and enantioselective intramolecular cyclic hydroboration to provide the intermediate cyclic trialkylborane. This trialkylborane, on treatment with an aldehyde, liberated the optically pure auxiliary as α-pinene (readily recovered for recycle) to provide the corresponding cyclic borinate ester. This ester reacted smoothly with α,α-dichloromethyl methyl ether (DCME) in the presence of a hindered base (the DCME reaction) to yield, after oxidation with buffered hydrogen peroxide, the trans-fused bicyclic or cyclic ketone in high enantiomeric excess (ee). In another improved approach, in situ generated IpcBHCl·Et2O, from the reduction of isopinocampheyldichloroborane (IpcBCl2) with trimethylsilane (Me3SiH), in the presence of representative dienes in Et2O provided considerably improved optical yields of the bicyclic and cyclic ketones. The trialkylboranes obtained from suitable acyclic dienes can be easily protonolyzed to provide the secondary alcohols in high ee.

Expanding the Substrate Specificity of Thermoanaerobacter pseudoethanolicus Secondary Alcohol Dehydrogenase by a Dual Site Mutation

“…13 C NMR (CDCl 3 ): δ = 14.0, 18.9, 39.1, 44.1, 72.4, 126.4, 128.5, 129.4, 138.6 ppm. The 1 H and 13 C NMR spectroscopic data were in accordance with those reported previously …”

Syntheses of Enantiopure Aliphatic Secondary Alcohols and Acetates by Bioresolution with Lipase B from Candida antarctica

“…The organic solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography using hexane and ethyl acetate as eluent to produce racemic alcohols 1 – 6 in excellent yields ( 1 , 70%; 2 , 95%; 3 , 92%; 4 , 97%; 5 , 94%; 6 , 93%). The spectroscopic data ( 1 H-NMR, MS and IR) of alcohols 1 , 2 , 4 and 6 agreed with the data reported in the literature [ 22 , 25 , 26 , 27 , 28 ].…”

“…The optical rotation of the products from the biocatalytic reaction was measured in a Perkin-Elmer (Waltham, MA, USA) model 241 polarimeter using a 1 dm cuvette and referenced to the Na–D line. The absolute configurations of compounds ( 1 , 4 – 6 , 12 ) were determined comparing the specific rotation signs measured for the products with that reported in the literature ( Table 3 ) [ 14 , 25 , 26 , 27 , 28 , 29 ]. The compounds 3 , 7 , 9 – 11 were suggested by empirical rule of Kazlauskas [ 5 , 24 ].…”

Rhodium(i)-catalyzed asymmetric [4 + 2] cycloaddition reactions of 2-alkylenecyclobutanols with cyclic enones through C–C bond cleavage: efficient access totrans-bicyclic compounds

“…The cyclohept-2-enone underwent annulation with 1a under optimal conditions leading to the [4.5.0] bicyclic products in moderate yield with an excellent ee value. This represents another type of important molecular scaffold 11 that is difficult to access using other methods ( Table 3 ).…”