Highly Selective Barbier‐Type Propargylations and Allenylations Catalyzed by Titanocene(III)

Abstract

The alkyne functional group is found in many bioactive natural products and is the key to many important chemical transformations developed over recent years. Moreover, allenes have recently gained relevance as versatile reagents in organic synthesis. Mild, catalytic methods to enable the selective introduction of either alkyne or allene motifs into organic molecules are very valuable but, as yet, quite scarce. We describe an extremely mild and selective method for either the propargylation or allenylation of carbonyl compounds catalyzed by the abundant, safe, and inexpensive metal titanium. These reactions can selectively provide homopropargylic alcohols from aldehydes and ketones or α-hydroxy-allenes from aldehydes. The mechanisms involved were also investigated.

Unprecedented Spectroscopic and Computational Evidence for Allenyl and Propargyl Titanocene(IV) Complexes: Electrophilic Quenching of Their Metallotropic Equilibrium

“…[13] These authors provided 13 CNMR chemical shifts for the intermediate species 3* as the only supporting data for the intermediates involved in this process, albeit in an inconclusive manner.S ome of us have recently expanded this Barbier-type methodt ot he synthesis of exocyclic allenes under mild conditions and have even applied the procedure to the synthesis of the natural alkaloid stemoamide. [14] In that contribution, am etallotropic equilibrium between ap ropargyl-Ti IV and an allenyl-Ti IV speciesi sp roposed.…”

“…As with other metals, it has been found that with titaniumi ntermediates, the relative ratio of products dependso nt he solvent, the nature of the propargyl halide,o rt he carbonyl substrate. [13] In fact, Oltra and co-workers have studied the reactivity of organotitanium species under variousc onditions, finding that terminal propargyl halides with aldehydes and ketones exclusively afford homopropargylicalcohols in all cases assayed. [13] NMR studies…”

“…[13] In fact, Oltra and co-workers have studied the reactivity of organotitanium species under variousc onditions, finding that terminal propargyl halides with aldehydes and ketones exclusively afford homopropargylicalcohols in all cases assayed. [13] NMR studies…”

“…For comparison purposes regarding the complexes synthesized herein,w ep rovide in Scheme 3a nd Scheme 4t he most relevant 1 Ha nd 13 CNMR data for all these complexes.…”

“…Mechanistically,t itanocene(III) complexes act to activate the halide of the electrophile by sequentiale lectron-transfer processes to generate transienta llyl or propargyl titanocene(IV) species that have never been characterized. [3][4][5][6][7] With respect to the applicationo fN MR methodologies towardst he unravellingof these titanocene derivatives, whether in catalytic or stoichiometricp rocesses, there are no literature precedents andt he data reported previouslyb yO ltra and coworkers [13] turned out to be inaccurate, as discussed below. In 1982, Yamamoto and co-workers described the synthesis of a-allenica nd b-acetylenic alcoholst hrough ap ropargyl tita-nium intermediate (1)o btaineda fter transmetalationo ft he corresponding lithiatedd erivativew ith [Ti(iPrO) 4 ]( Scheme 1).…”