Candice Botuha

High-Yielding Synthesis of Sphingoid-Type Bases

An efficient methodology for the synthesis of sphingoid-type bases is reported. It involves the stereoselective addition of a racemic 3-alkoxy allenylzinc to enantiopure N-tert-butylsulfinyl imines and a cross-metathesis reaction as the key steps. It has been successfully applied to the syntheses of sphinganine and naturally occurring bioactive related compounds, among which the hydrolysis product of clavaminol H and two spisulosines. All of these compounds have been prepared in six steps from N-tert-butylsulfinyl imines in high overall yields (>56%).

Allenylzinc reagents: new trends and synthetic applications

The last developments in our research efforts involving allenylzinc reagents are summarized. These interesting organometallic compounds allow the stereoselective and enantioselective synthesis of acetylenic epoxides, aziridines and amino alcohols. Some synthetic applications of these highly functionalized substrates are also presented through the synthesis of homopropargylic alcohols and allenic ketones. Further applications in the total synthesis of heterocyclic natural products are also discussed.

Expeditious Synthesis of a Common Intermediate of l-1-Deoxyallonojirimycin and l-1-Deoxymannojirimycin

The expeditious synthesis of a common intermediate of L-1-deoxyallonojirimycin (L-allo-DNJ) and L-1-deoxymannojirimycin (L-manno-DNJ) is reported. This intermediate is obtained in highly diastereo- and enantioselectivity with 38.4% overall yield in six steps involving the unprecedented ring-closing metathesis of a tert-butylsulfinyl allylamine as the key step.

Stereo- and enantioselective synthesis of acetylenic 2-amino-1,3-diol stereotriads.

The high-yielding and highly efficient stereoselective synthesis of enantiopure anti,anti and syn,anti acetylenic 2-amino-1,3-diol stereotriads from alpha-alkoxy-tert-butanesulfinylimines bearing a stereocenter alpha to the imino group is reported. The stereoselectivity of the reaction of these tert-butanesulfinyl (tBS)-imines with allenylzinc (+/-)-1 was found to be controlled only by the configuration of the tBS group. An excellent kinetic resolution of the racemic allenylzinc species was observed, allowing a high stereocontrol no matter what the configuration or the protecting group of the alpha-alkoxy group.

Carbometalation of unactivated alkenes by zinc enolate derivatives

The carbometalation reaction of zinc enolates and related stabilised organometallics on unactivated double bonds has emerged over the past decade as a mechanistically interesting and synthetically useful reaction. This Perspective is devoted to these challenging and apparently contra-thermodynamic transformations, with a special focus on recent mechanistic considerations involving radical–polar crossover reaction pathways.

Synthesis of R-(−)-2-phenylpropanal: a potentially new route towards chiral 2-phenylalkanals

Abstract A facile two step synthesis of ( R )-2-phenylpropanal in high enantiomeric excess is described, starting from commercial ( S )-styrene oxide, involving as a key step a Dess–Martin oxidation.

Access to Pyridyl-Substituted 1,3,5-Triazines from 4H-Pyrido[1,3]oxazin-4-ones via a Cyclocondensation Process

Pyridyl-substituted 1,3,5-triazines were synthesized in good to excellent yields via an unprecedented one-step cyclocondensation of 4H-pyrido[1,3]oxazin-4-ones with amidines at room temperature or under microwave irradiations. The broad applicability was demonstrated by 33 examples with a variety of amidines and three different 4H-pyrido[1,3]oxazin-4-one chemical series. In addition, a one-pot process from 4H-pyrido[1,3]oxazin-4-one precursors (imide sodium salts) was developed and led to the desired triazines compounds, thus allowing a one-step economy in their global synthetic preparation. This approach provides rapid access to pyridyl (or pyridone)-substituted 1,3,5-triazines with high potential in various fields of application.

Chiral Dawson-Type Hybrid Polyoxometalate Catalyzes Enantioselective Diels-Alder Reactions.

Can achiral organocatalysts linked to chiral polyanionic metal oxide clusters provide good selectivity in enantioselective C-C bond formations? The answer to this question is investigated by developing a new active hybrid polyoxometalate-based catalyst for asymmetric Diels-Alder reaction. Chirality transfer from the chiral anionic polyoxometalate to the covalently linked achiral imidazolidinone allows Diels-Alder cycloaddition products to be obtained with good yields and high enantioselectivities when using cyclopentadiene and acrylaldehydes as partners.

Expeditive access to 2-substituted 4H-pyrido[1,3]oxazin-4-ones via an intramolecular O-arylation.

Unreported 2-substituted 4H-pyrido[e][1,3]oxazin-4-ones are synthesized via an unprecedented intramolecular O-arylation of N-aroyl- and N-heteroaroyl-(iso)nicotinamides under microwave irradiations, in good to excellent yields. The broad applicability was demonstrated by 24 examples with a variety of substituents at the 2-position of the final compounds and 3 possible positions for the nitrogen atom of the pyridine ring. In addition, transformation of one of these compounds into 2-hydroxypyridyl-substituted 1,2,4-triazole and 1,2,4-oxazinone was realized. This approach opens a rapid access to a new bicyclic heteroaromatic chemical series with high potential in medicinal chemistry.

Cyclization of Zincated α‐N‐Homoallylamino Nitriles: A New Entry to Enantiopure 2,3‐Methanopyrrolidines

Stereoselective cyclization of zincated α-N-homoallylamino nitriles has been developed. Following treatment with lithium diisopropylamide (LDA) and transmetalation with zinc bromide, α-N-(1-phenylethyl)-N-homoallylamino nitriles lead to 2,3-methanopyrrolidines in moderate to good yields (up to 66u2009%) and excellent selectivities (up to >98:2). With substrates derived from α-branched homoallylic amines, a stereospecific inversion of the homoallylic stereogenic center was observed. To account for this, a mechanistic rationale involving the formation of zincioiminium ions from zincated α-amino nitriles is put forward. 2,3-Methanopyrrolidines should then arise from a sequence involving an aza-Cope rearrangement providing a configurationally stable (2-azoniaallyl)zinc species that then undergoes a [3+2] cycloaddition reaction.