Synthesis and Coordination Chemistry of Fluorine‐Containing Cages

Abstract

COMMUNICATIONS tion, one of the methoxy resonances was shifted upfield to b = 3.28 as a result of shielding of the methoxy group by the neighboring phenyl ring.r1b1 This group occupies a nearly orthogonal position, which would also explain the absence of dilactone formation after closure of the first lactone ring.In the final synthetic step a n intramolecular Pd-catalyzed Heck reaction was applied for the formation of the isoquinoline ring. This reaction afforded lamellarin G trimethyl ether (8) in 74 YO yield. To our knowledge, this is the first example of a Heck reaction in which after oxidative addition, the Pd" intermediate fragments by elimination of CO, . This method delivers the cyclization product 8 in higher yields than the conventional Heck reaction with the free pyrrole obtained by decarboxylation of 7.This short sequence (three steps) affords lamellarin G trimethyl ether (8) in 33% overall yield. Application of our method to the synthesis of other lamellarins, especially to those with unsymmetrically substituted aryl groups, is in progress. Since lamellarins of type 2 are easily dehydrogenated to the corresponding dihydroisoquinoline derivatives"'] by action of 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ), compounds of the latter type can also be obtained by our procedure. Experimental Section6: nBuLi (3.56 mL of a 2.5 M solution in hexane, 2.0 equiv) was added dropwise to a stirred solution 3-(3,4-dimethoxyphenyl)pyruvic acid (3) (1.0 g, 4.46 mmol) in dry T H F (80 mL) at -78 "C. After the mixture had been stirred for 20 min, a solution of iodine (0.56 g, 2.23 mmol, 0.5 equiv) in THF (20 mL) was added dropwise. The reaction mixture was allowed to warm up to room temperature, stirred for another hour, and then 2-(2-bromo-4,5-dimeth0xyphenyl)ethylammonium bromide (61 (5) (1.0 g, 2.93 mmol) was added and the resulting solution was stirred for 12 h over molecular sieves (4 A). The cloudy solution was quenched with 2 u NaOH. The layers were separated, the aqueous phase was washed with ethyl acetate (3 x 30 mL), acidified with concentrated HCI to pH 4. and extracted with ethyl acetate (3 x 30 cm3). The combined organic layers were dried (Na,SO,), filtered, and the organic solvent was removed in vacuo to give 1.9 g of crude material, which was recrystallized from methanol to yield 6 as a yellowish powder (1.39 g. 62%). M.p. 201 'C: UViVis (CHIOH): i.,,, (qualitative. nm) = 208, 288; ' H NMR (300.13 MHz,

Perturbation of 1JC,F Coupling in Carbon–Fluorine Bonds on Coordination to Lewis Acids: A Structural, Spectroscopic, and Computational Study

“…Candidate data sets include a diverse array of Lewis acidic sites, including multiple group 1 and 2 elements (lithium, ,, sodium, ,, potassium, , rubidium, cesium, , and calcium), as well as several transition elements (zirconium, , hafnium, and palladium). The aggregate data qualitatively agree with the statement that stronger C–F···LA interactions lead to lower 1 J C,F values: a simple plot of observed 1 J C,F versus coordinated C–F bond length shows a downward trend which, when fit to an empirical linear model ( R 2 = 0.64), suggests that 1 J C,F values decrease at a rate of about 6 Hz per 0.01 Å elongation (Figure S4).…”

“…Candidate data sets include a diverse array of Lewis acidic sites, including multiple group 1 and 2 elements (lithium, 13,28,29 sodium, 13,30,31 potassium, 13,32 rubidium, 33 cesium, 16,34 and calcium 35 ), as well as several transition elements (zirconium, 29,36 hafnium, 29 and palladium 37 ).…”

Synthesis of novel cage-annnulated fluoromacrocycles

“…In our hands, mono-O-benzylation of 2,2,3,3-tetrafluorobutane-1,4-diol (1) afforded 2 in 58% isolated yield. Subsequent base promoted reaction of 2 (2 equivalents) with 3,5-bis(2'-tosyloxyethyl)-4-oxahexacyclo[5.4.1.0 2,6 .0 3,10 .0 5,9 .0 8,11 ]-dodecane (3) 13 produced 4 (62% yield).…”

“…6 The high electronegativity and hardness of fluorine 7 render covalently bonded fluorine (C-F) suitable as an electron-pair donor for complexation with hard acceptors, e.g., alkali metal (Group I) and alkaline earth (Group II) metal cations, respectively. 8 Hitherto, we have demonstrated that cage-annulated crown ethers, 9 cryptands,clefts, 11 and molecular boxes, 12 constitute a new class of host systems for the study of host-guest interactions (i.e., molecular recognition and inclusion phenomena). Recently, we have undertaken the synthesis of some fluorine-containing analogs of these systems.…”

The first enantioselective syntheses of vicinal difluoropyrrolidines and the first catalytic asymmetric synthesis mediated by the C2 symmetry of a –CHFCHF– unit

“…2,5 Additionally, organofluoro ligands can be more powerful than oxygen ligands in coordinating metals. 8 Whereas enantiocontrolled syntheses of monofluoroorganic compounds are well established, synthesis of an enantiopure vicinal difluoro compound, especially of C 2 symmetry, has not to the best of our knowledge been reported prior to this communication. 9,10 Generally, molecular fluorine adds to alkenes with syn-stereoselection, thereby precluding the formation of C 2 symmetric difluorides; 11 where trans-addition is observed yields are usually low.…”