Resonance ionization of titanium: high useful yield and new autoionizing states

To facilitate analyses of trace amounts of titanium in atom-limited samples, we established a new three-step resonance ionization scheme. Using time-of-flight mass spectrometry we show that the new scheme can be easily saturated, yields stable isotope measurements, and can achieve an overall useful yield of 18%.

The Nakada Synthesis of (+)-Ophiobolin A

Ophiobolin A 3 shows nanomolar toxicity toward a range of cancer cell lines. A central feature of this sesterterpene, isolated from the rice fungus Ophiobolus miyabeanus, is the highly-substituted eight-membered ring. A key step in the synthesis of 3 described (Chem. Eur. J. 2013, 19, 5476; Angew. Chem. Int. Ed. 2011, 50, 9452) by Masahisa Nakada of Waseda University was the acid-mediated cyclization of 1 to 2. The preparation of 1 began with the enantioselective hydrolysis of 4 to the mono­ester 5. Selective reduction followed by protection gave 6, that was carried on via 7 to 8. The ethoxyethyl group was selectively removed, and the alcohol was converted to an iodide (not illustrated) that was condensed with the lactone 9 to give 1. The cyclization of 1 could jeopardize the stereogenic center adjacent to the masked carbonyl, so eight diastereomers were possible. Careful optimization led to a prepar­atively useful yield of the desired product 2. Hydroboration gave 10, that was carried on to the aldehyde 11. The cyclopentanone 15 was prepared from the enantiomerically-enriched epox­ide 12. Opening with vinyl magnesium bromide followed by exposure to the second-generation Grubbs catalyst gave the diol 13, that was selectively protected, leading to 14. The derived bromohydrin was a mixture of regioisomers and diastereomers, from which, after oxidation, 15 dominated. Generation of the boron enolate from 15 in the presence of 11 gave the aldol product, that could be dehydrated with the Burgess rea­gent. Reduction with Raney nickel set the stereogenic center adjacent to the ketone, that was carried on to 16. Metathesis to close the eight-membered ring was not trivial. Finally, it was found that 17 could be induced to cyclize to 18 at an elevated temperature using the second-generation Hoyveda catalyst. Protecting group exchange gave 19. Routine functional group manipulation then completed the synthesis of (+)-ophiobolin 3. Some years ago, Neil E. Schore of the University of California, Davis showed (Tetrahedron Lett. 1994, 35, 1153) that the opening of Sharpless-derived epoxides such as 12 with vinyl nucleophiles was unexpectedly flexible. One set of conditions gave the expected inversion, but alternative conditions led to opening with clean retention (or double inversion) of absolute configuration.

Understanding Site Selectivity in the Palladium-Catalyzed Cross-Coupling of Allenylsilanolates

Allenylsilanolates can undergo cross-coupling at the α- or γ-terminus, and site selectivity appears to be determined by the intrinsic transmetalation mechanism. Fine-tuning of concentration, nucleophilicity, and steric bulk of the silanolate moiety allows for the selective formation of one isomer over the other. Whereas the α-isomer can be obtained in synthetically useful yield, the γ-isomer is favored only when employing reaction conditions that are inevitably associated with diminished reactivity.

Functionalization of C-H Bonds: The Baran Synthesis of Dihydroxyeudesmane

Arumugam Sudalai of the National Chemical Laboratory, Pune reported (Tetrahedron Lett. 2008, 49, 6401) a procedure for hydrocarbon iodination. With straight chain hydrocarbons, only secondary iodination was observed. Chao-Jun Li of McGill University uncovered (Adv. Synth. Cat. 2009, 351, 353) a procedure for direct hydrocarbon amination, converting cyclohexane 1 into the amine 3. Justin Du Bois of Stanford University established (Angew. Chem. Int. Ed. 2009, 48, 4513) a procedure for alkane hydroxylation, converting 4 selectively into the alcohol 6. The oxirane 8 usually also preferentially ozidizes methines, hydroxylating steroids at the C-14 position. Ruggero Curci of the University of Bari found (Tetrahedron Lett. 2008, 49, 5614) that the substrate 7 showed some C-14 hydroxylation, but also a useful yield of the ketone 9. The authors suggested that the C-7 acetoxy group may be deactivating the C-14 C-H. C-H bonds can also be converted directly to carbon-carbon bonds. Mark E. Wood of the University of Exeter found (Tetrahedron Lett. 2009, 50, 3400) that free-radical removal of iodine from 10 followed by intramolecular H-atom abstraction in the presence of the trapping agent 11 delivered 12 with good diastereo control. Professor Li observed (Angew. Chem. Int. Ed. 2008, 47, 6278) that under Ru catalysis, hydrocarbons such as 13 could be directly arylated. He also established (Tetrahedron Lett. 2008, 49, 5601) conditions for the direct aminoalkylation of hydrocarbons such as 13, to give 17. Huw M. L. Davies of Emory University converted (Synlett 2009, 151) the ester 4 to the homologated diester 19 in preparatively useful yield using the diazo ester 18, the precursor to a selective, push-pull stabilized carbene. Intramolecular bond formation to an unactivated C-H can be even more selective. Guoshen Liu of the Shanghai Institute of Organic Chemistry developed (Organic Lett. 2009, 11, 2707) an oxidative Pd system that cyclized 20 to the seven-membered ring lactam 21 . Professor Du Bois devised (J. Am. Chem. Soc. 2008 , 130, 9220) a Rh catalyst that effected allylic amination of 22, to give 23 with substantial enantiocontrol. Dalibor Sames of Columbia University designed (J. Am. Chem. Soc. 2009, 131, 402) a remarkable cascade approach to C-H functionalization. Exposure of 24 to Lewis acid led to intramolecular hydride abstraction. Cyclization of the resulting stabilized carbocation delivered the tetrahydropyan 25 with remarkable diastereocontrol.