Syntheses of β- and γ-fluorophenyl cis- and trans-α-methylene-γ-butyrolactones

Preparation of a series of cis-γ-fluorophenyl-β-phenyl-α-methylene-γ-butyrolactones is reported via ‘allylboration’ of fluorobenzaldehydes with (E)-methyl 3-phenyl-2-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)acrylate. The corresponding trans-γ-fluorophenyl lactones were prepared either (i) via ‘allylboration’ using the (Z)-reagents or (ii) via an indium triflate-mediated isomerization of the cis-products. The difficulty in isomerizing difluorinated cis-products confirms the probable intermediacy of carbocations. Finally, the synthesis of cis-β-fluorophenyl-γ-phenyl-α-methylene-γ-butyrolactones was achieved via an indium-catalyzed allylation–lactonization of aldehydes with (Z)-2-(bromomethyl)-3-(fluorophenyl)acrylates.     

Synthesis of α-hydroxyalkyl dehydroazepanes via catalytic enantioselective borylative migration of an enol nonaflate

A Pd-catalyzed borylative migration methodology for cyclic enol perfluorosulfonates was applied to the synthesis of the corresponding 7-membered, azepane ring system. Throughout the optimization, it was shown that the reaction is sensitive to the nitrogen protecting group as well as the type of base and solvent. The resulting cyclic allylboronate reacts stereoselectively with aldehydes for the synthesis of novel α-hydroxyalkyl dehydroazepanes in good yield and enantioselectivity over two steps. We highlight the utility of this methodology with an efficient synthesis of the de novo 7-membered ring analogue of the piperidine alkaloid β-conhydrine.     

Synthetic studies toward the pyran core and the amide side chain of psymberin

A synthetic approach to the polysubstituted pyran core and amide side chain of psymberin (irciniastatin A) using stereoselective organoboron methodology is described. An advanced oxyranyl pyran intermediate was prepared using a catalytic enantioselective and diastereoselective three-component reaction involving first an inverse electron-demand hetero [4+2] cycloaddition between 3-boronoacrolein pinacolate and 1-ethoxy-2-methylpropene, followed by an allylboration of ethyl glyoxylate. The amide side chain was prepared highly efficiently using the first example of a doubly diastereoselective allylboration of a chiral α-alkoxy aldehyde under the Lewis acid-catalyzed reaction manifold.     

Catalytic Homologation-Allylboration Sequence for Diastereo- and Enantioselective Synthesis of Densely Functionalized β-Fluorohydrins with Tertiary Fluoride Stereocenters

Homologation of trisubstituted fluoroalkenes followed by allylboration of aldehyde, ketone and imine substrates is suitable for synthesis of β-fluorohydrin and amine products. In the presence of (R)-iodo-BINOL catalyst enantioselectivities up to 99 % can be achieved by formation of a single stereoisomer with adjacent stereocenters, of which one is a tertiary C−F center.     

Baylis-Hillman chemistry: a one pot cross-coupling/allylboration reaction

A one pot sequential cross-coupling/allylboration is described. Baylis-Hillman acetate adducts couple with bis(pinacolato)diboron to form substituted allylboronates, which react with aldehydes in the presence of a silica supported BF₃ catalyst to form highly functionalized homoallylic alcohols in excellent yields.     

First synthesis of (+)-8-methoxygoniodiol and its analogue, 8-deoxygoniodiol, using a three component strategy

We have described the first total synthesis of the natural product, (+)-8-methoxygoniodiol, and its analogue, 8-deoxygoniodiol using a catalytic asymmetric hetero-Diels-Alder/allylboration sequence involving three partners. The cytotoxic activity of these final compounds and of two synthetic intermediates has been evaluated against human cancer cell lines (A375P and A375M), showing the importance of the lactone moiety.     

Conformationally constrained amino acids: enantiodivergent synthesis of all four stereoisomers of 2-(tetrahydrofuran-2-yl)glycine

The first enantiodivergent synthesis of all four possible 2-(tetrahydrofuran-2-yl)glycine stereoisomers is described. The key step of the route is the highly stereocontrolled allylboration of the (S)- or (R)-Garner's aldehydes to give four chiral homoallylalcohols. Starting from them, the title compounds are obtained in five steps.     

γ-Fluorophenyl-GABA derivatives from fluorobenzonitriles in high diastereomeric and enantiomeric excess

An enantioselective synthesis of α-fluoroaryl homoallylic amines in 52-71% yields and 76-93% enantioselectivities has been achieved via the allylboration of the corresponding fluorinated N-aluminobenzaldimines with B-allyldiisopinocampheylborane in the presence of methanol, followed by alkaline hydrogen peroxide workup. Crotylboration of these aluminobenzaldimines with potassium B-methoxy B-E- or -Z-crotyldiisopinocampheylborinate provided the corresponding β-anti- or -syn-methyl α-fluoroarylhomoallylamines, respectively in high de and ee. Similarly, alkoxyallylboration with lithium B-methoxy B-γ-OMEMallyldiisopinocampheylborinate provided the corresponding β-syn-alkoxyhomoallylamines in excellent de and ee. Representatives of these amino alkenes were converted to the corresponding optically active N-Boc-protected fluorinated amino alcohols via hydroboration-oxidation. Further chromium-mediated oxidation provided N-Boc-protected γ-fluorophenyl-γ-aminobutyric acids, which upon deprotection provided the corresponding γ-lactams.     

Allylic boranes are chemist’s best friends: Reactivity, applications, new opportunities

Fruitful methods for the preparation of various (poly)unsaturated, (poly)cyclic and cage organic compounds with the use of allylic type organoboranes have been developed. Allylborane reactions proceeding with the rearrangement of allylic moiety or via a direct rupture of the B-C bond (with retention) little known to the boron community are considered. Synthesis of boron containing clathrochelates and some transformations of 1-boraadamantane, a unique cage compound, are also described.     

Efficient synthesis of chiral C2-symmetric diamines via allylboration of bis-N,N′-metallodiimines

An enantioselective synthesis of C₂-symmetric bis-homoallylic aromatic and heteroaromatic diamines in 54-89% yields, in 73-94% de and ?98% ee has been achieved via the allylboration of the corresponding N,N′-bis(trimethylsilyl)dialdimines and N,N′-bis(diisobutylalumino)dialdimines with B-allyldiisopinocampheylborane in the presence of methanol, followed by alkaline hydrogen peroxide workup. One-pot synthesis of stable N,N′-bis(benzaldimine-triethylborane) complexes and subsequent allylboration to afford benzene diamines is also described.