Synthesis of a Nonracemic C-Symmetric Tetrahydro-1,4-azaborine and Evaluation of Hydroboration Enantioselectivity.

Tetrahydro-1,4-azaborines were accessed by hydroboration of N,N-diprenyltoluenesulfonamide 4. Conversion to the methylborinates 11 and 12 followed by heating with l-alanine and crystallization afforded (R,R,S)-13 (27%). Reduction of borinic acid (R,R)-18 with Soderquist's KH* gave (R,R)-19, and hydride abstraction by TMSCl in the presence of alkenes resulted in hydroboration, 84-86% ee for (Z)-alkenes, but (E)-alkenes or 1,1-disubstituted alkenes gave <5% ee.

Development of a Chiral DMAP Catalyst for the Dynamic Kinetic Resolution of Azole Hemiaminals.

A new catalyst for the dynamic kinetic resolution of azole hemiaminals has been developed using late-stage structural modifications of the tert-leucinol-derived chiral subunit of DMAP species.

Enantiocontrolled synthesis of a tetracyclic aminal corresponding to the core subunit of diazonamide A.

A chiral benzylic ether serves as an auxiliary for oxindole carboxylation (dr 5.2:1.0) that sets C10 configuration in a potential diazonamide precursor.

Stereoselective synthesis of the diazonamide a macrocyclic core.

Stereoselective synthesis of the right-hand heteroaromatic macrocycle of diazonamide A features C16-C18 bond formation in the Suzuki-Miyaura cross-coupling and atropodiastereoselective Dieckmann-type macrocyclization as key steps. The Suzuki-Miyaura cross-coupling gave the best yields when it was catalyzed by a palladium-dioxygen complex.

Electrophilic C-H Borylation and Related Reactions of B-H Boron Cations.

Catalytic procedures are described for aminedirected borylation of aliphatic and aromatic tertiary amine boranes. Sequential double borylation is observed in cases where two or more C-H bonds are available that allow 5-center or 6-center intramolecular borylation. The HNTf catalyzed borylation of benzylamine boranes provides a practical means for the synthesis of ortho-substituted arylboronic acid derivatives, suitable for Suzuki-Miyaura cross-coupling applications.

Weakly stabilized primary borenium cations and their dicationic dimers.

Hydride abstraction from monocationic hydride bridged salts [H(H2B-L)2](+) [B(C6F5)4]¯ (L = Lewis base) generates an observable primary borenium cation for L = iPr2NEt, but with L = Me3N, Me2NPr, or several N-heterocyclic carbenes, highly reactive dicationic dimers are formed.

P-directed borylation of phenols.

Internal borylation occurs upon activation of aryl di-isopropylphosphinite boranes with HNTf(2) to give heterocyclic intermediates that can be reductively quenched to afford 6 or treated with KHF(2) to give the phenolic potassium aryl trifluoroborate salts 10. The latter salts are useful for Pd-catalyzed coupling with aryl iodides under Molander conditions, provided that precautions are taken to remove the KNTf(2) byproduct from the preceding KHF(2) step.

Borenium ion catalyzed hydroboration of alkenes with N-heterocyclic carbene-boranes.

Treatment of alkenes such as 3-hexene, 3-octene, and 1-cyclohexyl-1-butene with the N-heterocyclic carbene (NHC)-derived borane 2 and catalytic HNTf(2) (Tf = trifluoromethanesulfonyl (CF(3)SO(2))) effects hydroboration at room temperature. With 3-hexene, surprisingly facile migration of the boron atom from C(3) of the hexyl group to C(2) was observed over a time scale of minutes to hours. Oxidative workup gave a mixture of alcohols containing 2-hexanol as the major product.

Mechanistic variations in ionic hydrogenation of unsaturated phosphine and amine boranes.

Internal hydride transfer occurs when tethered carbocations are generated from unsaturated phosphine or phosphinite boranes. 3-Methylenecyclohexyl-derived boranes 12 or 18 react with MsOH to give ionic hydrogenation products with high syn-selectivity. With unsaturated amine boranes, initial hydrogen evolution gives BH(2)(OMs) complexes, but IH occurs using excess MsOH in a slower second stage.

Reactivity of aziridinomitosene derivatives related to FK317 in the presence of protic nucleophiles.

The syntheses and reactivity of N-TBDPS and N-trityl protected derivatives of an aziridinomitosene corresponding to FK317 are described. New reactivity patterns were observed for these highly sensitive and functionally dense heterocycles under mild nucleophilic conditions approaching the threshold for degradation. Thus, the silyl or trityl protected aziridinomitosene reacted with Cs(2)CO(3)/CD(3)OD to give isomeric products where substitution occurred at C(10) and C(9a) (mitomycin numbering) providing a CD(3) ether and a CD(3) hemiaminal, respectively.

N-Directed aliphatic C-H borylation using borenium cation equivalents.

Highly electrophilic boron cations derived from hindered amine borane complexes have been shown to undergo intramolecular aliphatic C-H borylation.

Metalated aziridines for cross-coupling with aryl and alkenyl halides via palladium catalysis.

The palladium-catalyzed coupling of an aziridinylzinc chloride intermediate with alkenyl and aryl halides has been demonstrated. The method provides products with retention of aziridine stereochemistry. The utility of the coupling procedure is illustrated in the synthesis of structures related to l-furanomycin.

Aziridinomitosanes via lactam cyclization.

Aziridinomitosane ketones 4 and 24 are accessed by internal acyl anion equivalent-lactam cyclization of 29 in a convergent route. The key aziridinolactam 6 is prepared by tin-lithium exchange via the lithiated aziridine 11.

Catalytic parallel kinetic resolution under homogeneous conditions.

Two complementary chiral catalysts, the phosphine 8d and the DMAP-derived ent-23b, are used simultaneously to selectively activate a mixture of two different achiral anhydrides as acyl donors under homogeneous conditions. The resulting activated intermediates 25 and 26 react with the racemic benzylic alcohol 5 to form enantioenriched esters (R)-24 and (S)-17 by fully catalytic parallel kinetic resolution (PKR). The aroyl ester (R)-24 is obtained with near-ideal enantioselectivity for the PKR process, but (S)-17 is contaminated by ca.

Superelectrophilic intermediates in nitrogen-directed aromatic borylation.

The first examples of borylation under conditions of borenium ion generation from hydrogen-bridged boron cations are described. The observable H-bridged cations are generated by hydride abstraction from N,N-dimethylamine boranes Ar(CH(2))(n)NMe(2)BH(3) using Ph(3)C(+) (C(6)F(5))(4)B(-) (TrTPFPB) as the hydride acceptor. In the presence of excess TrTPFPB, the hydrogen-bridged cations undergo internal borylation to afford cyclic amine borane derivatives with n = 1-3.

Stereocontrol in N-directed hydroboration: synthesis of amino alcohols related to the piperidine alkaloids.

Treatment of 2-(2'-alkenyl)-piperidine boranes with iodine or triflic acid induces internal hydroboration with high regiocontrol, even with a terminal alkene (R = H). Good stereocontrol is possible for the N-benzyl substrates. Comparisons with acyclic model structures show that the source of regiocontrol with the terminal alkene is due to a steric effect of the axial piperidine C(3,5) hydrogens that destabilize the competing bridged bicyclic transition state.

AcOLeDMAP and BnOLeDMAP: conformationally restricted nucleophilic catalysts for enantioselective rearrangement of indolyl acetates and carbonates.

The rate of indolyl O- to C-acetyl or carboxyl rearrangement is accelerated by the electron-withdrawing N-diphenylacetyl group (DPA) using the conformationally restricted chiral catalysts AcOLeDMAP (12b) and BnOLeDMAP (13b). Highly enantioselective conversion to quaternary C-acetylated and C-carboxylated oxindoles is observed, even for substrates containing branched substituents. The rearrangement of the carboxylate substrates 19 occurs with complementary enantiofacial selectivity using catalyst 13b compared to the acetyl migrations of 16 catalyzed by 12b.

Formation of pinacol boronate esters via pyridine iodoborane hydroboration.

Hydroboration of alkenes with pyridine iodoborane followed by treatment with pinacol/NaOH affords monoalkyl pinacol boronates in moderate to good yield. Dialkylborinic acid derivatives are formed competitively, especially in the case of terminal alkenes. This side reaction can be minimized by using excess of pyridine iodoborane.

Oxygen-directed intramolecular hydroboration.

Metal-free homoallylic oxygen-directed intramolecular hydroboration is reported. Regioselectivities from 20:1 to 82:1 favoring the 1,3-dioxy-substituted products have been achieved using Me2S.BH3/TfOH followed by standard oxidative workup.

Amine-directed hydroboration: scope and limitations.

Iodine activation induces intramolecular hydroboration of homoallylic and bis-homoallylic amine boranes with good to excellent control of regiochemistry compared to control experiments using excess THF*BH 3. Deuterium labeling and other evidence confirm that the iodine-induced hydroboration reaction of homoallylic amine boranes occurs via an intramolecular mechanism equivalent to the classical 4-center process and without competing retro-hydroboration. Longer carbon chain tethers result in lower regioselectivity, whereas the shorter tether in allylic amines results in a switch to dominant intermolecular hydroboration.