Search

Irish Research Council (Project Numbers GOIPG/2013/1064 and GOIPG/2013/225); Science Foundation Ireland (Grant Number 02/PICA/B802/EC07)

The hazardous diazo transfer reagent mesyl azide, has been safely generated and used in situ for continuous diazo transfer as part of an integrated synthetic process with an embedded safety quench. Diazo transfer to β-ketoesters and a β-ketosulfone was successful. In-line phase separation, by means of a continuous liquid-liquid separator, enabled direct telescoping with a thermal Wolff rearrangement.

This review focuses on the synthesis and reactivity of thioketone S-oxides (sulfines). Sulfines have been long established as being reactive intermediates of high interest and with potential for wide application in organic synthesis. The review will cover many aspects of sulfines: the first section looks at the different routes to the synthesis of these compounds with a detailed look at more recently developed routes; the second section details the scope of reactivity of these types of compounds and how they are useful in synthetic organic chemistry with a particular look at cycloaddition and nucleophilic addition reactions.

Both the efficiency and the stereoselectivity in baker's-yeast-mediated reduction of ketones are strongly influenced by both the presence and the position of sulfur substituents, or indeed by the use of sulfur-containing additives. Interestingly the oxidation level of the sulfur substituent has a powerful impact on the outcome of the yeast reduction. It is apparent that use of the sulfone moiety as a substituent to influence the efficiency and stereoselectivity in ketone reduction is substantially more effective than use of the analogous sulfide and sulfoxide moieties.

Laser flash photolysis (λexc = 266 nm) of α-sulfinyl diazo compound 1b results in the formation of two transient phenomena. Transient absorption A (intense, λmax = 275 nm) shows jump-and-growth behaviour with a growth lifetime of τ = 2 μs. Transient absorption B (weak, λmax = 415 and 540 nm) decays with a lifetime of τ = 1.8 μs, which suggests that B decays into A. On the basis of a comparison with calculated UV/Vis spectra, transient absorption B is assigned to triplet carbene 37. DFT and CCSD(T) calculations indicate that carbene 7 should have a singlet (S) ground state with a singlet–triplet energy gap of ca. 11 kcal mol–1 in acetonitrile solution. The seemingly paradoxical observation of a triplet excited state of a ground-state singlet carbene is rationalised in terms of the very different geometries of the singlet and triplet carbene; the most prominent difference lies in the pyramidalisation at the sulfoxide sulfur atom. For the singlet carbene 17, the O–S–C:–C(=O) dihedral angle is calculated to be 172.8°, whereas it is –80.0° for the triplet carbene 37. Therefore, for efficient intersystem crossing (ISC) to occur, the triplet carbene must significantly change its geometry. A triplet–singlet minimum energy crossing point (MECP) was located with an O–S–C:–C(=O) dihedral angle of –141.3°. On the basis of the energy of this MECP (15.2 kcal mol–1 above the S carbene in CH3CN) and on the ISC rate constant of diphenyl carbene taken as preexponential factor, a rate for the ISC of 37 is estimated that matches the experimental value within one order of magnitude.

Enantiopure β-nitro alcohols are key chiral building blocks for the synthesis of bioactive pharmaceutical ingredients. The preparation of these target compounds in optically pure form has been the focus of much research and there has been an emergence of biocatalytic protocols in the past decade. For the first time, these biotransformations are the focus of this review. Herein, we describe two principal biocatalytic approaches to the Henry (nitroaldol) reaction. The first method is a direct enzyme-catalysed carbon–carbon bond formation resulting in either an enantio-enriched or enantiopure β-nitro alcohol. The second approach describes the Henry reaction without stereocontrol followed by a biocatalytic resolution to yield the enantiopure β-nitro alcohol.

The photochemistry of the α-diazo sulfoxide 7 has been investigated in solid argon at 10 K by IR spectroscopy. The sulfinyl carbene was not detected directly but instead underwent photochemically induced hetero-Wolff rearrangement to the sulfine 8 which could be detected and characterized following irradiation at 248 nm. Further photochemical reaction of this intermediate led to the oxathiirane 9 which was most readily detected on irradiation of 7 at 308 nm. The matrix-isolated species were identified by comparison of experimental and calculated IR spectra. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

The photochemistry of the α-diazo sulfoxides 1a and 1b has been investigated in solid argon at 10 K by IR and UV/Vis spectroscopy. Both diazo compounds react to form sulfine 2a by photochemically induced hetero Wolff rearrangement of sulfinyl carbene 3, which itself cannot be detected in solid argon. Irradiation at λ > 320 nm results in decomposition of the sulfine 2a to give 2-oxa-4-thiabicyclo[4.4.0]decane-3.5-dione (5) and 7-oxabicyclo[4.2.0]octan-8-one (6) under abstraction of COS. The matrix-isolated species have been identified by comparison of experimental and calculated IR spectra.