Carlos González-Rodríguez

DABCO-Bis(sulfur dioxide), DABSO, as a Convenient Source of Sulfur Dioxide for Organic Synthesis: Utility in Sulfonamide and Sulfamide Preparation

The charge-transfer complex generated from the combination of DABCO and sulfur dioxide, DABSO, is a bench-stable colorless solid suitable for use in organic synthesis as a replacement for gaseous sulfur dioxide. The complex can be combined with Grignard reagents to form sulfinates, which can then be converted in situ to a series of sulfonamides. Alternatively, reaction with anilines and iodine leads to the formation of a series of sulfamides. Cheletropic addition between DABSO and 2,3-dimethylbutadiene provides the corresponding sulfolene.

Aryl methyl sulfides as substrates for rhodium-catalyzed alkyne carbothiolation: arene functionalization with activating group recycling.

A Rh(I)-catalyzed method for the efficient functionalization of arenes is reported. Aryl methyl sulfides are combined with terminal alkynes to deliver products of carbothiolation. The overall process results in reincorporation of the original arene functional group, a methyl sulfide, into the products as an alkenyl sulfide. The carbothiolation process can be combined with an initial Rh(I)-catalyzed alkene or alkyne hydroacylation reaction in three-component cascade sequences. The utility of the alkenyl sulfide products is also demonstrated in simple carbo- and heterocycle-forming processes. We also provide mechanistic evidence for the course of this new process.

Cycloisomerization of aromatic homo- and bis-homopropargylic alcohols via catalytic Ru vinylidenes: formation of benzofurans and isochromenes.

Ru-catalyzed cycloisomerizations of aromatic homo- and bis-homopropargylic alcohols effectively afford benzofurans and isochromenes. These processes proved to be chemo- and regioselective (5-, and 6-endo cyclizations) derived from key Ru vinylidene intermediates. The presence of an amine/ammonium base-acid pair is crucial for the catalytic cycle.

Rhodium‐Catalyzed Branched‐Selective Alkyne Hydroacylation: A Ligand‐Controlled Regioselectivity Switch

Its all in the ligand: By choice of the appropriate diphosphine ligand a previously linear-selective alkyne hydroacylation process can be “switched” to be highly branched-selective (see scheme, l=linear, b=branched). Structural data for the ortho-iPr-dppe–rhodium catalyst suggest restricted rotation of the phosphine aryl units may be responsible for the observed selectivity.

Brønsted Acid-Promoted Intramolecular Carbocyclization of Alkynals Leading to Cyclic Enones

TFA-promoted exo carbocyclizations of nonterminal 7-alkynals gave good to excellent yields of seven-membered cycloalkenones, a medium-sized functionalized ring present in natural products with relevant pharmacological properties. Nonterminal 5- and 6-alkynals also gave very good yields of the corresponding exo cyclopentenones and cyclohexenones. On the other hand, terminal 5-alkynals gave endo carbocyclizations to cyclohexenones. These carbocyclizations can be considered as tandem alkyne hydration/aldol condensation processes.

Replacing dichloroethane as a solvent for rhodium-catalysed intermolecular alkyne hydroacylation reactions: the utility of propylene carbonate

Propylene carbonate is an excellent solvent for rhodium-catalysed intermolecular alkyne hydroacylation reactions, allowing a variety of β-S-aldehydes and alkynes to be combined in high yields, to deliver enone products. The effective use of propylene carbonate removes the need to employ dichloroethane as solvent.

Nucleophilic Addition of Amines to Ruthenium Carbenes: ortho‐(Alkynyloxy)benzylamine Cyclizations towards 1,3‐Benzoxazines

A new ruthenium-catalyzed cyclization of ortho-(alkynyloxy)benzylamines to dihydro-1,3-benzoxazines is reported. The cyclization is thought to take place via the vinyl ruthenium carbene intermediates which are easily formed from [Cp*RuCl(cod)] and N2 CHSiMe3 . The mild reaction conditions and the efficiency of the procedure allow the easy preparation of a broad range of new 2-vinyl-2-substituted 1,3-benzoxazine derivatives. Rearrangement of an internal C(sp) in the starting material into a tetrasubstituted C(sp(3) ) atom in the final 1,3-benzoxazine is highly remarkable.

Rhodium-catalyzed enantioselective intermolecular hydroacylation reactions*

Rhodium-catalyzed enantioselective hydroacylation reactions allow rapid access to chiral substituted ketones. However, due to the low reactivity of disubstituted alkenes in intermolecular versions of this process, only a small number of asymmetric intermolecular reactions have been described. Strategies employed to avoid reactivity issues include the use of norbornadienes, linear dienes, acrylamides, and allenes as the alkene components. In addition, our laboratory has recently reported the rhodium-catalyzed enantioselective inter-molecular alkyne hydroacylation reaction, leading to the formation of enone products via a kinetic resolution procedure.

Rhodium-Catalysed Intermolecular Alkyne Hydroacylation: The Enantioselective Synthesis of α- and β-Substituted Ketones by Kinetic Resolution

The potential utility of transition-metal-catalysed alkene and alkyne hydroacylation reactions—readily available substrates, synthetically useful products and inherently atom economic processes—has resulted in considerable interest in these transformations over the last decade. During this time one of the main goals has been to develop efficient intermolecular variants that do not suffer decarbonylation. Stabilisation of key reaction intermediates by the use of chelating substrates has proven to be one successful approach, albeit with certain substrate constraints remaining. In addition, a number of methods that avoid the need for chelation control have also been described. Recently, attention has turned to the development of enantioselective variants of these processes, and although a number of intramolecular reactions are known, examples of intermolecular transformations remain scarce. The enantioselective intermolecular reactions that have been reported all require specific substrate combinations: Bolm and Stemmler were the first to report an enantioselective intermolecular reaction; they employed norbornene-type alkenes in combination with salicylaldehyde derivatives to obtain varied selectivities and yields. Suemune et al. have combined salicylaldehyde derivatives with dienes in a process that proceeds with moderate to good enantioselectivities but mixed regiocontrol. Tanaka and Shibata have developed a highly enantioselective intermolecular process that requires the use of 1,1-substituted acrylamide derivatives as the alkene component. Our own laboratory has also been active in this area and reported an enantioselective allene hydroacylation process that employed b-S-substituted aldehydes. It follows that the need to employ specific substrate classes results in the formation of products with only limited substitution patterns. The constraints in substrate choice needed to achieve an enantioselective intermolecular hydroacylation reaction result mainly from the relatively poor reactivity of disubstituted alkenes in these types of processes. We postulated that the greater reactivity of alkyne substrates could result in a more general asymmetric process; however, to deliver products incorporating a stereogenic centre the reactions would need to operate as kinetic resolutions, employing appropriately substituted, and racemic, aldehydes (Scheme 1). In addition to the greater reactivity we hoped to achieve by employing alkyne substrates, the proposed kinetic resolutions would also deliver more complex enonecontaining products (compare 1!2 with 3!4 and 5!6, Scheme 1). Although enantioselective intramolecular alkyne

Tandem Brønsted Acid Promoted and Nazarov Carbocyclizations of Enyne Acetals to Hydroazulenones

NOTICE: This is the peer reviewed version of the following article:Escalante, L., Gonzalez-Rodriguez, C., Varela, J. A., Saa, C. (2012). Tandem Bronsted Acid Promoted and Nazarov Carbocyclizations of Enyneacetals to Hydroazulenones. Angew. Chem. Int. Ed., 51, 49, 12316-12320. [doi: 10.1002/anie.201205823]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for self-archiving.