Theodore Cohen

Reductive Lithiation of Some Thioketals Using Lithium 1-(Dimethylamino)naphthalenide

Abstract Recent work from this laboratory has demonstrated that readily prepared lithium naphthalenide (2) at -70° is capable of the rapid reductive lithiation of cyclopropanone dithioketals (1) to sulfur-stabilized cyclopropyllithiums (4),1 ketene phenylthio-acetals (8) to sulfur-stabilized vinyllithiums (9) which are acyl anion equivalents,2 and a 1,1,3-tris(phenylthio)alkene (11) to the lithio derivative (12) of an α,β-unsaturated thioacetal.3,4

Regio- and Enantioselective Iridium-Catalyzed Allylation of Thiophenol: Synthesis of Enantiopure Allyl Phenyl Sulfides

A highly regio- and enantioselective allylic alkylation of sodium thiophenoxide has been realized by [Ir(COD)Cl](2)/phosphoramidite along with CsF as an additive, producing highly enantioenriched allyl phenyl sulfide compounds with up to 99% ee.

Reductive metallation : A general preparative method for hydrocarbon allylmetallic compounds

Abstract Because of the great ease of preparation of allyl phenyl sulfides and their smooth reductive lithiation using lithium naphthalenide or 1-(dimethylamino)naphthalenide, these are ideal substrates for a particularly versatile preparative method for allylic anions. The lithio compounds react with aldehydes and ketones readily and with moderate regioselectivity. The allyltitanium compounds formed by addition of titanium tetraisopropoxide react with enals with very high regioselectivity and stereoselectivity. The allyltilanium compound derived from 2-phenylthio-1-methylenecyclohexane adds in a 1,2-fashion to crotonaldehyde at the secondary terminus of the allylic system. The potassium salt of this adduct undergoes the anion-accelerated oxy Cope rearrangement to the product of formal 1,4-addition of the crotonaldehyde to the primary terminus. The rearrangement product is an aldehyde which is also synthetically useful, undergoing the Lewis acid catalyzed ene reaction to produce a ring-closed product.

A synthesis of 2-vinylcylobutanones using 1-methoxycyclopropyllithium reagents

Abstract A facile synthesis of 2-vinylcyclobutanones consists of reductive lithiation of 1-phenylthio-1-methoxycyclopropanes) addition of enals or enones to the resulting α-lithioethers, and acid catalyzed rearrangement of the allylic alcohols thus produced.

A novel one-flask cyclopentannulation involving a dilithiomethane equivalent as a β-connector of two enones. A highly efficient total synthesis of (±)-hirsutene

Abstract Five- and six-membered rings can be constructed in one flask from two different enones and tris(phenylthio)methyllithium. The latter behaves as a dilithiomethane equivalent when its central carbon atom adds in conjugate fashion to one enone, becomes nucleophilic again when one of its phenylthio groups is exchanged for lithium in the presence of sec -butyllithium, and then undergoes conjugate addition to a second enone to provide a dienolate dianion. The latter can be oxidized to a 1,4-diketone incorporating a cyclopentane ring or induced to undergo an aldol reaction to produce a six-membered ring. In some of the cases, an interesting stereochemical equilibration occurs during the oxidation leading to one of two possible diastereomers and the overall process results in a highly efficient, stereospecific synthesis of (±)-hirsutene 13 .

Enantio- and diastereoselective tandem zn-promoted brook rearrangement/ene-allene carbocyclization reaction.

The zinc-catalyzed addition of various alkynes to acylsilanes followed by a Zn-Brook rearrangement and either the Zn-ene-allene or Zn-yne-allene cyclization led to the enantio- and diastereoselective formation of carbocycles in a single-pot operation.

Remarkable stereocontrol in the addition of an anion to an α- alkoxyaldehyde by encouraging or discouraging internal complexation. Applications to brief syntheses of the mus musculus (house mouse) pheromone and exo-brevicomin

Abstract Stereoselective addition of ethylmetallic reagents to acrolein dimer 1 and the conversion of the threo alchol 4t to exo -brevicomin and the Mus musculus pheromone are reported.

Cerium(III) chloride remarkably increases the rates of formation and yields of ketones in the reaction of lithium carboxylates with organolithiums

Abstract The presence of CeCl 3 greatly increases the yield of ketones in the reaction of organolithiums with lithium carboxylates. The Ce III suppresses the enolization of the lithium carboxylate, previously unrecognized as a competing reaction except in special cases, and the formation of tertiary alcohols. One of the reasons for the latter effect is a surprising increase in the rate of addition of the organometallic to the lithium carboxylate in the presence of Ce III .

A method for methylidenation and ethylidenation of an allylic thioether leading to a 2,3-sigma-tropic rearrangement. Failure of the Simmons-Smith reaction in the presence of thioethers

Abstract Allylic phenylthioethers are converted in one step to homoallylic phenylthioethers by treatment with methylene iodide or ethylidene iodide in the presence of diethylzinc but not zinc—copper or zinc—silver couples; furthermore, Simmons-Smith cyclopropanation of cyclohexane is unsuccessful in the presence of various thioethers.

Highly efficient terpenoid pheromone syntheses via regio and stereocontrolled processing of allyllithiums generated by reductive lithiation of allyl phenyl thioethers

Abstract Previous work had shown that reducuve lithiation of allyl phenyl thioethers, followed by transmetallation, produces allylmetallics which react selectively with carbonyl compounds at the most or least substituted terminus; the latter results in mainly cis olefin. This technology allows extremely efficient syntheses of racemic versions of lavandulol (two-pot, 70% yield), the Comstock mealy bug pheromone (one-pot, 45% yield) and the California red scale pheromone (4-steps, 23% yield).