Richard F. W. Jackson

A new method for the preparation of tertiary butyl ethers and esters

T-butyl 2,2,2-trichloroacetimidate (1), readily prepared by addition of t-butanol to trichloroacetonitrile, is an efficient reagent for the preparation of t-butyl ethers and esters in the presence of a catalytic amount of boron trifluoride etherate.

Much improved conditions for the Negishi cross-coupling of iodoalanine derived zinc reagents with aryl halides.

A combination of Pd(2)(dba)(3) and SPhos (1:2 molar ratio) is an excellent precatalyst for the Negishi cross-coupling of the serine-derived organozinc reagent 2 with aryl halides, including previously difficult ortho-substituted examples. In the case of meta- and para-substituted aryl halides, Pd-loadings of 0.5 mol % give satisfactory results. Use of 2-iodoaniline as substrate gives the lactam 12 in good yield.

Synthesis of enantiomerically pure protected β-aryl alanines

Abstract The organozinc reagent (1), prepared from the β-iodoalanine derivative (2), reacts with aryl iodides at 50 °C in the presence of catalytic bis(tri-o-tolylphosphine)palladium dichloride to give in moderate to good yields enantiomerically pure protected S-β-aryl alanine derivatives (4).

Catalytic asymmetric epoxidation of aliphatic enones using tartrate-derived magnesium alkoxidesElectronic supplementary information (ESI) available: conditions for enantiomeric purity determination for epoxyketones derived by di-tert-butyl tartrate mediated epoxidation. See http://www.rsc.org/suppdata/cc/b1/b109421a/

Simple aliphatic enones can be converted into the corresponding epoxides in 71–93% ee using tert-butylhydroperoxide in the presence of a catalyst derived from dibutylmagnesium and di-tert-butyl tartrate.

A new direct method for the synthesis of enantiomerically pure protected α-amino acids

The organozinc reagent (2), prepared from the protected β-iodo alanine derivative (3) using ultrasonic activation, is efficiently acylated using acid chlorides in the presence of (Ph3P)2PdCl2 to give high yields of enantiomerically pure protected γ-keto α-amino acids (4).

Optimization of New Chiral Ligands for the Copper‐Catalysed Enantioselective Conjugate Addition of Et2Zn to Nitroolefins by High‐Throughput Screening of a Parallel Library

A library of chiral ligands 5, obtained with a modular building block strategy from the coupling of sulfonyl chlorides 1a−e, amines 2f−j and aldehydes 4p−t, was screened in the enantioselective, copper-catalysed conjugate addition of Et2Zn to aromatic and heteroaromatic nitroolefins 6a−e. A multisubstrate high-throughput screening was realised by performing the addition reactions on an equimolar mixture of substrates 6c−d. Good ligands for the addition reaction to nitroolefins 6a−e (ee’s up to 58%) were identified.

Structure Elucidation of Dimethylformamide-Solvated Alkylzinc Cations in the Gas Phase

Organozinc iodides, useful for the synthesis of nonproteinogenic amino acids, are investigated in the gas phase by a combination of electrospray (ESI)-MS/MS, accurate ion mass measurements, and infrared multiphoton dissociation (IRMPD) spectroscopy employing a free electron laser. ESI allowed the full characterization of a set of dimethylformamide (DMF)-solvated alkylzinc cations formed by formal loss of I(-) in the gas phase. Gas phase ion structures of the organozinc cations were identified and optimized by computations at the B3LYP/6-311G** level of theory. The calculations indicate that the zinc cation in gas phase alkylzinc-DMF species preferentially adopts a tetrahedral coordination sphere with four ligands, namely the alkyl group, any internal coordinating group, and DMF (the number of which depends on the number of internal coordinating groups present). Besides the sequential loss of coordinated DMF, collision-induced dissociation (CID) patterns demonstrate that the zinc-DMF interaction in tetrahedral four-coordinate mono-DMF-zinc complex ions can be even stronger than covalent bonds. The IRMPD spectra of the alkylzinc-DMF species examined show a rich pattern of indicative bands in the range of 1000-1800 cm(-1). All major features of the recorded IRMPD spectra are consistent with the computed IR spectra of the respective gas phase ion structures predicted by theory, allowing identification and assignment.

Synthesis of protected 4-oxopipecolic acid and 4-oxolysine using a palladium-catalysed coupling process

Abstract Reaction of the L -serine derived zinc reagent 3 with acryloyl chloride gave the 4-oxo amino acid 4 , with no evidence of products arising from conjugate addition. Treatment of the adduct 4 with benzylamine gave protected 4-oxolysine 5 directly. Reduction of the ketone proceeded without significant stereoselectivity to give the 4-hydroxylysine derivatives 6 as a diastereoisomeric mixture. Treatment of the adduct 4 with HCl/ether gave 4-oxopipecolic acid benzyl ester hydrochloride 7 in quantitative yield. Evidence for initial formation of the HCl adduct 8 was obtained.

New syntheses of bullatenone and geiparvarin

Abstract New convenient syntheses of two 3(2H)-furanone natural products bullatenone (1) and geiparvarin (2) are described involving the hydration of the corresponding readily accessible acetylenic ketones. These are best made by a Pd (II) - Cu (I) catalysed coupling process.

Short, stereoselective syntheses of 4,5,6-trihydroxylated norleucines : an approach to the synthesis of (+)-bulgecinine

Abstract Reaction of the L -serine derived zinc reagent 1 with D -isopropylideneglyceryl chloride gave the 4-oxo amino acid 5 , which was reduced with high diastereoselectivity to give the trans -lactone 7 . Analogous reaction of the D -serine derived zinc reagent gave the the 4-oxo amino acid 6 , which was reduced with high diastereoselectivity to give the cis -lactone 8 . Conversion of 8 to 11 , the enantiomer of the Boc-protected analogue 10 of an intermediate in Fleets synthesis of (−)-bulgecinine, was achieved in two steps.