WO2016196514A1

WO2016196514A1 - Thiourea catalysts

Info

Publication number: WO2016196514A1
Application number: PCT/US2016/035099
Authority: WO
Inventors: Steven KASS; Yang FAN; Masoud SAMET
Original assignee: Regents Of The University Of Minnesota
Priority date: 2015-06-01
Filing date: 2016-05-31
Publication date: 2016-12-08

Abstract

The invention provides thiourea catalysts of formula I: wherein A and B have any of the values defined in the specification. The catalysts are useful for carrying out new chemical bond forming reactions (e.g., Friedel-Crafts reactions).

Description

THIOUREA CATALYSTS

Priority of Invention

This application claims priority to U.S. Provisional Patent Application No. 62/169,371, filed on June 1, 2015, the entirety of which is incorporated herein by reference.

Government Funding

This invention was made with government support under CHE- 1462014 and CHE- 1361766 awarded by the National Science Foundation. The government has certain rights in the invention.

Background of the Invention

Currently there is a need for catalysts that can be used in forming new chemical bonds (e.g., carbon-carbon bond, carbon-nitrogen bond, and carbon-sulfur bond).

Summary of the Invention

A new and powerful thiourea catalyst has been developed that is more active than existing thiourea catalysts. The higher activity is beneficial because it allows for lower catalyst loadings, lower reaction temperatures, higher selectivities, and/or the ability to induce transformations that less reactive catalysts cannot. The catalysts of the invention are metal-free, non-corrosive, and air/water stable.

Accordingly in one embodiment the invention provides a catalyst that is a compound of formula I:

H H (I)

wherein:

A is a 5-15 membered heteroaryl comprising one or more nitrogen atoms in an aromatic ring, wherein the 5-15 membered heteroaryl is optionally substituted with one or more groups

independently selected from H, halo, hydroxyl, nitro, cyano, trifluoromethoxy, (C₁-Ci2)alkyl, (C₃- C₈)cycloalkyl, (C₃-C₆)cycloalkyl(Ci-C₆)alkyl, (C_rC₆)alkoxy, (C C₆)alkanoyl,

(C₁-C6)alkoxycarbonyl, and (C2-C₆)alkanoyloxy, wherein each (Cj-Ci2)alkyl, (C₃-C8)cycloalkyl, (C₃- C6)cycloalkyl(C]-C6)alkyl, (Ci-C6)alkanoyl, (C C₆)alkoxycarbonyl, and (C₂-C6)alkanoyloxy is optionally substituted with one or more groups independently selected from halo and wherein one or more of the nitrogen atoms in an aromatic ring is a positively charged tetravalent nitrogen associated with an anion; B is a 6-10 membered aryl or a 5-15 membered heteroaryl comprising one or more nitrogen atoms in an aromatic ring, wherein 6-10 membered aryl and the 5-15 membered heteroaryl are optionally substituted with one or more groups independently selected from H, halo, hydroxyl, nitro, cyano, trifluoromethoxy, (Ci-C₁₂)alkyl, (C3-C₈)cycloalkyl, (C3-C6)cycloalkyl(C]-C6)alkyl, (Q- Ce)alkoxy, (C₁-C₆)alkanoyl, (C₁-C6)alkoxycarbonyl, and (C₂-C6)alkanoyloxy, wherein each (Ci-

Ci₂)alkyl, (C₃-C₈)cycloalkyl, (C3-C₆)cycloalkyl(C_rC₆)alkyl, (Ci-C₆)alkanoyl, (C₁-C₆)alkoxycarbonyl, and (C2-C₆)alkanoyloxy is optionally substituted with one or more groups independently selected from halo and wherein one or more of the nitrogen atoms in an aromatic ring, if present, is optionally a positively charged tetravalent nitrogen associated with an anion.

The invention also provides a method for forming a carbon-carbon bond, comprising reacting a first reactant with a second reactant in the presence of a compound (e.g., a catalyst) as described herein under conditions such that a carbon-carbon bond forms between the first compound and the second compound.

The invention also provides processes and intermediates disclosed herein that are useful for preparing a compound of formula I or a salt thereof.

Detailed Description

The following definitions are used, unless otherwise described: halo is fluoro, chloro, bromo, or iodo. Alkyl, alkoxy, etc. denote both straight and branched groups; but reference to an individual radical such as propyl embraces only the straight chain radical, a branched chain isomer such as isopropyl being specifically referred to. Aryl denotes a phenyl radical or an ortho-fused bicyclic carbocyclic radical having about nine to ten ring atoms in which at least one ring is aromatic.

Heteroaryl encompasses a radical of a monocyclic aromatic ring containing five or six ring atoms consisting of carbon and one to four heteroatoms each selected from the group consisting of non- peroxide oxygen, sulfur, and N(X) wherein X is absent or is H, O, (C₁-C4)alkyl, phenyl or benzyl, as well as a radical of monocyclic or polycyclic (e.g., 2 or 3 rings) heterocycle such as a heteroaryl of about 5 to 15 ring atoms comprising one to four heteroatoms each selected from the group consisting of non-peroxide oxygen, sulfur, and N(X), as well as a radical of an ortho-fused bicyclic heterocycle such as a heteroaryl of about eight to ten ring atoms comprising one to four heteroatoms each selected from the group consisting of non-peroxide oxygen, sulfur, and N(X). Specific values listed below for radicals, substituents, and ranges, are for illustration only; they do not exclude other defined values or other values within defined ranges for the radicals and substituents

Specifically, (Ci-Ci₂)alkyl can be methyl, ethyl, propyl, isopropyl, butyl, iso-butyl, sec-butyl, pentyl, 3-pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, or dodecyl; (C3-Cg)cycloalkyl can be cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; (C₃-C6)cycloalkyl(Ci- C6)alkyl can be cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, 2- cyclopropylethyl, 2-cyclobutylethyl, 2-cyclopentylethyl, or 2-cyclohexylethyl; (C₁-C₆)alkoxy can be methoxy, ethoxy, propoxy, isopropoxy, butoxy, iso-butoxy, sec-butoxy, pentoxy, 3-pentoxy, or hexyloxy; (Ci-C6)alkanoyl can be acetyl, propanoyl or butanoyl; (Cj-C6)alkoxycarbonyl can be methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, pentoxycarbonyl, or hexyloxycarbonyl; (C₂-C6)alkanoyloxy can be acetoxy, propanoyloxy, butanoyloxy, isobutanoyloxy, pentanoyloxy, or hexanoyloxy; aryl can be phenyl, indenyl, or naphthyl; and heteroaryl can be furyl, imidazolyl, triazolyl, triazinyl, oxazoyl, isoxazoyl, thiazolyl, isothiazoyl, pyrazolyl, pyrrolyl, pyrazinyl, tetrazolyl, pyridyl, (or its N-oxide), thienyl, pyrimidinyl (or its N-oxide), pyridazyl (or its N-oxide), pyrazinyl (or its N-oxide), indolyl, isoquinolyl (or its N- oxide) or quinolyl (or its N-oxide).

As used herein the term "anion" refers to any anion such as but not limited to a negatively charged element or compound. The term anion as used herein when associated with a heteroaryl which contains a positively charged tetravalent ring nitrogen, refers to an anion that is a counterion to the positively charged tetravalent ring nitrogen atom of the heteroaryl. Non-limiting examples of anions include (a) halo anions such as F^" CI^", Br^", and Γ; (b) ^~B(Ar)₄, anions wherein each Ar is independently selected from the group consisting of 6-10 membered aryl and 5-10 membered heteroaryl, wherein each 6-10 membered aryl and 5-10 membered heteroaryl is optionally substituted with one or more groups independently selected from halo, hydroxyl, nitro, cyano, trifluoromethoxy (Ci-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(Ci-C₆)alkyl, (d-C^alkoxy, (Ci-C₆)alkanoyl, (Ci-C₆)alkoxycarbonyl, and (C₂-C6)alkanoyloxy, wherein any (CrC₆)alkyl, (C₃-C6)cycloalkyl, (C₃- C6)cycloalkyl(Ci-C6)alkyl, (C₁-C6)alkoxy, (C₁-C₆)alkanoyl, (Ci-C6)alkoxycarbonyl, and (C₂- C6)alkanoyloxy is optionally substituted with one or more groups independently selected from halo; and (c) other anions such as BF₄ ^~, PF₆ ^~, Al(OC(CF₃)₃)₄ ^~, and carboranes such as HCBnMesB^ and It is to be understood that the following embodiments provided include values for compounds of formula I and all subformulas thereof (e.g., compounds of formula la, lb, Ic) and for methods using said compounds. It is to be understood that two or more of the embodiments may be combined.

-15 membered heteroaryl selected from:

wherein the 5-15 membered heteroaryl is optionally substituted with one or more groups independently selected from H, halo, hydroxyl, nitro, cyano, trifluoromethoxy, (Ci-Ci₂)alkyl, (C₃- C₈)cycloalkyl, (C3-C₆)cycloalkyl(C₁-C₆)alkyl, (Ci-C₆)alkoxy, (C_rC₆)alkanoyl,

(Ci-C₆)alkoxycarbonyl, and (C₂-C₆)alkanoyloxy, wherein each (Ci-Ci₂)alkyl, (C₃-C₈)cycloalkyl, (C₃- C6)cycloalkyl(C₁-C₆)alkyl, (C₁-C₆)alkanoyl, (Ci-C₆)alkoxycarbonyl, and (C₂-C₆)alkanoyloxy is optionally substituted with one or more groups independently selected from halo and wherein one or more of the nitrogen atoms in an aromatic ring is a positively charged tetravalent nitrogen associated with an anion.

In one embodiment B is a 6-10 membered aryl or a 5-15 membered heteroaryl selected from:

wherein the 6-10 membered aryl and the 5-15 membered heteroaryl are optionally substituted with one or more groups independently selected from H, halo, hydroxyl, nitro, cyano,

trifluoromethoxy, (C₁-C₁₂)alkyl, (C₃-C₈)cycloalkyl, (C₃-C₆)cycloalkyl(Ci-C₆)alkyl, (Ci-C₆)alkoxy, (Ci-C₆)alkanoyl, (CrC^alkoxycarbonyl, and (C₂-C6)alkanoyloxy, wherein each (Ci-C₁₂)alkyl, (C₃- Cg)cycloalkyl, (C₃-C6)cycloalkyl(C₁-C6)alkyl, (C₁-C6)alkanoyl, (Ci-C₆)alkoxycarbonyl, and (C₂- C₆)alkanoyloxy is optionally substituted with one or more groups independently selected from halo and wherein one or more of the nitrogen atoms in an aromatic ring, if present, is optionally a positively charged tetravalent nitrogen associated with an anion.

In one embodiment A is selected from:

wherein one or more of the nitrogen atoms in an aromatic ring is further substituted with a group selected from H, (Ci-Ci₂)alkyl, (C₃-C₈)cycloalkyl, or (C₃-C₆)cycloalkyl(C _rC6)alkyl, wherein each (Ci-Ci2)alkyl, (C₃-C8)cycloalkyl, and (C3-C6)cycloalkyl(Ci-C₈)alkyl is optionally substituted with one or more groups independently selected from halo, providing one or more positively charged tetravalent nitrogen atoms associated with an anion. In one embodiment A is selected from:

wherein the nitrogen atom in an aromatic ring is further substituted with a group selected from H, (C_rCi₂)alkyl, (C₃-C₈)cycloalkyl, or (C₃-C₆)cycloalkyl(Ci-C₆)alkyl, wherein each (Ci-Ci₂)alkyl, (C₃- Cg)cycloalkyl, and (C3-C6)cycloalkyl(Ci-C₈)alkyl is optionally substituted with one or more groups independently selected from halo, providing the positively charged tetravalent nitrogen atoms associated with an anion.

In one embodiment A is selected from:

wherein the nitrogen atom in an aromatic ring is further substituted with (Ci-Ci2)alkyl, optionally substituted with one or more groups independently selected from halo, providing the positively charged tetravalent nitrogen atoms associated with an anion.

In one embodiment A is selected from:

and is associated with an anion.

In one embodiment B is selected from:

wherein one or more of the nitrogen atoms in an aromatic ring is optionally further substituted with a group selected from H, (Ci-C)2)alkyl, (C3-C₈)cycloalkyl, or (C₃-C6)cycloalkyl(CrC6)alkyl, wherein each (Ci-C₁₂)alkyl, (C₃-C₈)cycloalkyl, and (C3-C6)cycloalkyl(Ci-C₈)alkyl is optionally substituted with one or more groups independently selected from halo, optionally providing one or more positively charged tetravalent ring nitrogen atoms associated with an anion.

In one embodiment B is selected from:

wherein one or more of the nitrogen atoms in an aromatic ring is optionally further substituted with a group selected from H, (C₁-C₁₂)alkyl, (C3-C8)cycloalkyl, or (C3-C6)cycloalkyl(Ci-C₆)alkyl, wherein each (Ci-C₁2)alkyl, (C₃-Cg)cycloalkyl, and (C3-C6)cycloalkyl(Ci-Cg)alkyl is optionally substituted with one or more groups independently selected from halo, optionally providing one or more positively charged tetravalent ring nitrogen atoms associated with an anion.

In one embodiment B is selected from:

wherein the nitrogen atoms in an aromatic ring is optionally further substituted with a group selected from H, (Ci-C_]2)alkyl, (C₃-C₈)cycloalkyl, or (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, wherein each (Cj- C₁₂)alkyl, (C3-Cg)cycloalkyl, and (C₃-C6)cycloalkyl(Ci-Cg)alkyl is optionally substituted with one or more groups independently selected from halo, optionally providing the positively charged tetravalent ring nitrogen atoms associated with an anion.

In one embodiment B is selected from:

wherein the nitrogen atoms in an aromatic ring is optionally further substituted with (Ci-Ci₂)alkyl, optionally substituted with one or more groups independently selected from halo, providing the positively charged tetravalent ring nitrogen atoms associated with an anion.

In one embodiment B is selected from:

providing the positively charged tetravalent ring nitrogen atoms associated with an anion.

In one embodiment the compound of formula I is a com ound of formula la:

wherein: Y is ⁺N-R¹ T ^a;

Z is CH or ^-R^{2 ~}X^b;

R¹ is H, (Ci-Ci₂)alkyl, (C₃-C₈)cycloalkyl, or (C₃-C₆)cycloalkyl(Ci-C₆)alkyl, wherein each (d C₁₂)alkyl, (C₃-C₈)cycloalkyl, and (C₃-C6)cycloalkyl(CrC )alkyl is optionally substituted with one or more groups independently selected from halo;

R² is H, (Ci-C₎₂)alkyl, (C₃-C₈)cycloalkyl, or (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, wherein each (Ci Ci₂)alkyl, (C₃-Cg)cycloalkyl, and (C₃-C6)cycloalkyl(C₁-C₈)alkyl is optionally substituted with one or more groups independently selected from halo;

X^a is an anion; and

X^b is an anion.

In one embodiment the compound of formula I is a compound of formula lb:

(ft).

In one embodiment the compound of formula I is a compound of formula Ic:

In one embodiment Z is CH.

In one embodiment Z is ^-R^{2 ~}X^b.

In one embodiment R¹ is H.

In one embodiment R¹ is (C₁-Ci₂)alkyl, optionally substituted with one or more groups independently selected from halo.

In one embodiment R¹ is methyl or octyl.

In one embodiment R¹ is methyl.

In one embodiment R¹ is octyl.

In one embodiment R² is H.

In one embodiment R is (Ci-Ci₂)alkyl optionally substituted with one or more groups independently selected from halo.

In one embodiment R is methyl or octyl.

In one embodiment R² is methyl. In one embodiment R² is octyl.

In one embodiment a formula I is a compound of formula Id:

(Id)

wherein:

Y is ¾-R' ^~X^a;

R¹ is H, (Q-C^alkyl, (C₃-C₈)cycloalkyl, or (C₃-C₆)cycloalkyl(Ci-C₆)alkyl, wherein each (Ci- Ci₂)alkyl, (C₃-C₈)cycloalkyl, and (C₃-C6)cycloalkyl(Ci-C8)alkyl is optionally substituted with one or more groups independently selected from halo; and

X^a is an anion.

In one embodiment a formula I is a compound of formula le:

wherein:

Y is ⁺N-R^{1 ~}X^a;

R¹ is H, (Q-C^alkyl, (C₃-C₈)cycloalkyl, or (C₃-C₆)cycloalkyl(Ci-C6)alkyl, wherein each (d- Cn)alkyl, (C3-C₈)cycloalkyl, and (C₃-C6)cycloalkyl(Ci-C₈)alkyl is optionally substituted with one or more groups independently selected from halo; and

X^a is an anion.

In one embodiment R¹ is H.

In one embodiment R¹ is (Ci-C]₂)alkyl, optionally substituted with one or more groups independently selected from halo.

In one embodiment R¹ is methyl or octyl.

In one embodiment R¹ is methyl.

In one embodiment R¹ is octyl.

In one embodiment X^a is CI^", Br^", or Γ.

In one embodiment X^a is Γ. In one embodiment X^a is T¾(Ar)4, wherein each Ar is independently selected from the group consisting of 6-10 membered aryl and 5-10 membered heteroaryl, wherein each 6-10 membered aryl and 5-10 membered heteroaryl is optionally substituted with one or more groups independently selected from halo, hydroxyl, nitro, cyano, trifluoromethoxy (C Ce^lkyl, (C3-C₆)cycloalkyl, (C₃- C6)cycloalkyl(Ci-C6)alkyl, (Ci-C6)alkoxy, (Ci-C6)alkanoyl, (Ci-C6)alkoxycarbonyl, and (C₂-

C6)alkanoyloxy, wherein any (Ci-C6)alkyl, (C₃-C6)cycloalkyl, (C₃-C₆)cycloalkyl(Ci-C₆)alkyl, (Q- C₆)alkoxy, (Ci-C6)alkanoyl, (CrC₆)alkoxycarbonyl, and (C₂-Ce)alkanoyloxy is optionally substituted with one or more groups independently selected from halo.

In one embodiment X^a is TB(3,5-bis(trifluoromethyl)phenyl)4.

In one embodiment X^b is CI^", Br^", or Γ.

In one embodiment X^b is Γ.

In one embodiment X^b is ^~B(Ar)₄, wherein each Ar is independently selected from the group consisting of 6-10 membered aryl and 5-10 membered heteroaryl, wherein each 6-10 membered aryl and 5-10 membered heteroaryl is optionally substituted with one or more groups independently selected from halo, hydroxyl, nitro, cyano, trifluoromethoxy (Ci-C₆)alkyl, (C₃-C6)cycloalkyl, (C₃- C6)cycloalkyl(Ci-C₆)alkyl, (Ci-Ce)alkoxy, (CrC₆)alkanoyl, (C₁-C6)alkoxycarbonyl, and (C₂- C₆)alkanoyloxy, wherein any (C]-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, (C C₆)alkoxy, (Ci-C₆)alkanoyl, (CrC₆)alkoxycarbonyl, and (C₂-C6)alkanoyloxy is optionally substituted with one or more groups independently selected from halo.

In one embodiment X^b is ^~ B(3,5-bis(trifluoromethyl)phenyl)₄.

In one embodiment the anion is CI^", Br^", or Γ.

In one embodiment the anion is Γ.

In one embodiment the anion is ^~B(Ar)₄, wherein each Ar is independently selected from the group consisting of 6-10 membered aryl and 5-10 membered heteroaryl, wherein each 6-10 membered aryl and 5-10 membered heteroaryl is optionally substituted with one or more groups independently selected from halo, hydroxyl, nitro, cyano, trifluoromethoxy (Ci-C₆)alkyl, (C₃- C₆)cycloalkyl, (C₃-C₆)cycloalkyl(Ci-C₆)alkyl, (C_rC₆)alkoxy, (Q-C_f alkanoyl,

(C₁-C6)alkoxycarbonyl, and (C₂-C6)alkanoyloxy, wherein any (Ci-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃- C₆)cycloalkyl(C]-C₆)alkyl, (Ci-C₆)alkoxy, (C₁-C₆)alkanoyl,

and (C₂- C6)alkanoyloxy is optionally substituted with one or more groups independently selected from halo. In one embodiment the method for forming a carbon-carbon bond, comprising reacting a first reactant with a second reactant in the presence of a compound as described herein (e.g., a catalyst of formula I, la, lb, Ic) under conditions such that a carbon-carbon bond forms between the first compound and the second compound.

In one embodiment the com ound of formula I is selected from:

wherein each Ar is 3,5-bis(trifluoromethyl)phenyl. In one embodiment the compound of formula I is selected from:

4

wherein each Ar is 3,5-bis(trifluoromethyl)phenyl.

In one embodiment of the method described herein the formed carbon-carbon bond described herein has an enantiomeric excess greater than 50%.

In one embodiment of the method described herein the formed carbon-carbon bond described herein has an enantiomeric excess greater than 80%.

In one embodiment of the method described herein the formed carbon-carbon bond described herein has an enantiomeric excess greater than 85%.

In one embodiment of the method described herein the compound described herein is selected from:

In one embodiment of the method described herein the compound as described herein (e.g., a catalyst of formula I, la, lb, Ic, Id, le) is present in a catalytic amount.

In one embodiment of the method described herein the compound as described herein (e.g., a catalyst of formula I, la, lb, Ic, Id, le) is present in an amount of less than about 15 mole percent with respect to the first reagent. In one embodiment of the method described herein the compound as described herein (e.g., a catalyst of formula I, la, lb, Ic, Id, le) is present in an amount of less than about 5 mole percent with respect to the first reagent.

In one embodiment of the method described herein the compound as described herein (e.g., a catalyst of formula I, la, lb, Ic, Id, le) is present in an amount of less than about 1 mole percent with respect to the first reagent.

In one embodiment of the method described herein the compound as described herein (e.g., a catalyst of formula I, la, lb, Ic, Id, le) is present in an amount of less than about 0.1 mole percent with respect to the first reagent.

In one embodiment of the method the reacting is carried out in a solvent.

In one embodiment of solvent comprises a halocarbon solvent or toluene.

Thiourea catalysts (3 and 4 below) were synthesized as illustrated in Schemes 1 and 2.

Catalysts 5-11 were prepared in an analogous way.

Ar = 3,5-bis(trifluoromethyl)phenyl Scheme 1

Ar = 3,5-bis(trifluoromethyi)phenyl

Scheme 2

The ability of a compound of the invention to act as a catalyst was determined in new chemical bond forming reactions, such as Friedel-Crafts reaction, Diels-Alder reaction and aminolysis of styrene oxide. The reactivity of thiourea catalysts 3-11 was compared to previously reported and commercially available compounds 1 and 2. The latter compound 2 is often referred to as Schreiner's thiourea and is typically considered to be the most active thiourea available.

The invention will now be illustrated by the following non-limiting examples. Example 1. Preparation of Catalys

Scheme 1

Ar = 3,5-bis(trifluoromethyl)phenyl

Step 1. Preparation of V-methyI-3-isothiocyanatopyridinium

3-Isothiocyanatopyridine (0.20 g, 1.47 mmol) was dissolved in 2 mL of ethyl acetate in a vial under argon and iodomethane (0.18 mL, 2.89 mmol) was added dropwise at room temperature with stirring. The resulting precipitate that formed overnight was filtered and washed with 5 mL of ethyl acetate to afford 0.25 g (61%) of N-methyl-3-isothiocyanatopyridinium iodide as a pale yellow solid. Ή NMR (300 MHz, DMSO-d₆) δ 9.32 (s, 1H), 8.93 (d, J= 6.0 Hz, 1H), 8.62 (d, J= 9.0 Hz, 1H), 8.17 (dd, J= 6.0 and 9.0 Hz, 1H), 4.32 (s, 3H).

Step 2. Preparation of l-methyl-3- -phenylthioureido)pyridinium iodide

N-Methyl-3-isothiocyanatopyridinium iodide (0.15 g, 0.54 mmol) was dissolved in 3 mL of acetonitrile under argon in a vial and aniline (55 μΐ , 0.60 mmol) was added dropwise at room temperature with stirring. The resulting precipitate that formed overnight was filtered and washed with 5 mL of acetonitrile to give 0.14 g (70%) of the product as a pale yellow solid. 'H NMR (300 MHz, DMSO-d₆) δ 10.57 (s, 1H), 10.43 (s, 1H), 9.25 (s, 1H), 8.69 (d, J= 5.9 Hz, 1H), 8.55 (d, J= 9.5 Hz, 1H), 8.05 (dd, J= 6.2 and 8.8 Hz, 1H), 7.43 (m, 4H), 7.23 (t, J= 7.5 Hz, 1H), 4.34 (s, 3H).

Step 3. Preparation of 3

3

Sodium tetrakis(3,5-bis(trifluoromethyl)phenyl)borate (24 mg, 27 μιηοΐ) and 10 mg (27 μηιοΐ) of l -methyl-3-(3-phenylthioureido)pyridinium iodide were transferred to a vial and 1 mL of dichloromethane was added. This mixture was stirred under argon at room temperature until the solids dissolved and a cloudy suspension resulted. Stirring was then stopped and the solution was left undisturbed until a white solid precipitated and a clear solution formed. Filtration of the reaction mixture and removal of the solvent under reduced pressure afforded 25 mg (84%) of 3 as a yellow solid. ^JH NMR (500 MHz, CD₂C1₂) δ 9.91 (s, 1H), 8.40 (br s, 1H), 8.1 1 (m, 2H), 8.03 (br s, 1H), 7.83 (t, J= 6.5 Hz, 1H), 7.73 (s, 8H), 7.56 (s, 4H), 7.54 (t, J= 7.5 Hz, 2H), 7.46 (t, J= 7.5 Hz, 1H), 7.37 (d, J= 8.0 Hz, 2H), 4.35 (s, 3H).

Example 2. Preparation of Catalyst 4

Scheme 2

Ar = 3,5-bi

4

Step 1. Preparation of l,3-bis-3- -methylpyridylium)thiourea iodide

N-Methyl-3-isothiocyanatopyridinium iodide (0.10 g, 0.36 mmol) was dissolved in 3 mL of acetonitrile under argon in a vial and N-methyl-3-aminopyridinium iodide (85 mg, 0.36 mmol) was added with stirring at room temperature. The resulting precipitate that formed overnight was filtered and washed with 5 mL of acetonitrile to give 0.10 g (52%) of the product as a pale yellow solid. *H NMR (300 MHz, DMSO-d₆) 5 1 1.09 (br s, 2H), 9.23 (s, 2H), 8.79 (d, J= 6.0 Hz, 2H), 8.60 (d, J = 8.7 Hz, 2H), 8.13 (dd J= 6.0 and 8.7 Hz, 2H), 4.38 (s, 6H).

Step 2. Preparation of 4

4

Sodium tetrakis(3,5-bis(trifluoromethyl)phenyl)borate (34 mg, 39 μιηοΐ) and 10 mg (19 μπιοΐ) of l,3-bis-3-(l-methylpyridylium)thiourea iodide were transferred to a vial and 1 mL of dichloromethane was added. This mixture was stirred at room temperature under argon until the solids dissolved and a cloudy suspension formed. Stirring was then stopped and the solution was left undisturbed until a white solid precipitated and a clear solution resulted. Filtration of the reaction mixture and removal of the solvent under reduced pressure afforded 32 mg (85%) of 4 as a yellow solid. Ή NMR (300 MHz, CD₂C1₂) δ 10.00 (br s, 2H), 9.69 (s, 2H), 8.35 (d, J= 8.7 Hz, 2H), 8.19 (d, J= 6.3 Hz, 2H), 7.89 (dd, J= 5.9 and 8.5 Hz, 2H), 7.72 (s, 16H), 7.55 (s, 8H), 4.34 (s, 6H).

Example 3. Preparation of Catalyst 6

6

Step 1. Preparation of 3-isothiocyanato-l-(l-octyl)pyridinium triflate

OTf

In a 6 dram vial, 0.10 g (0.73 mmol) of 3-isothiocyanatopyridine was dissolved in 1 mL of ethyl acetate and 0.39 g (1.47 mmol) of 1-octyl triflate (S. Kyasa et al. J. Org. Chem. 2015, 80, 12100-121 14) was added at room temperature under argon. The reaction mixture was allowed to stir overnight and 2 mL of pentane was added. Stirring was then stopped and the solution was left undisturbed until two organic layers were formed. The lower layer was isolated and dried under vacuum to afford 0.25 g (86%) of product as a brown oil.

Step 2. Preparation of l-(l-octyl)-3-(3-phenylthioureido)pyridinium triflate (6)

6

In a 6-dram vial, 0.10 g (0.25 mmol) of 3-isothiocyanato-l-(l-octyl)pyridinium triflate was dissolved in 1 mL of ethyl acetate under argon. Aniline (24

0.26 mmol) was added and the reaction mixture was allowed to stir overnight at room temperature. A minimal amount of pentane was subsequently added (~ 2mL) and the resulting precipitated oil was isolated and dried under vacuum to afford 85 mg (69%) of product as a brown oil. Example 4. Preparation of Catalyst 5

5

To a 6 dram vial, 0.15 g (0.17 mmol) of sodium tetrakis(3,5- bis(trifluoromethyl)phenyl)borate, 85 mg (0.17 mmol) of l-(l-octyl)-3-(3- phenylthioureido)pyridinium triflate and 2 mL of CH₂CI₂ were added. This mixture was stirred at room temperature under an argon atmosphere until the solid material was totally dissolved and a cloudy suspension formed. Stirring was then stopped and the solution was left undisturbed until a white solid precipitated and a clear solution formed. The reaction mixture was then filtered and concentrated under reduced pressure to afford 0.18 g (88%) of product as a brown oil.

Example 5. Preparation of Catalyst 7

Scheme 3

Ar = 3

Step 1. Preparatio -bis-3-(l-(l-octyI)pyridylium)thiourea tosylate

In a 6 dram vial, 0.10 g (0.73 mmol) of 3-isothiocyanatopyridine was dissolved in 2 mL of ethyl acetate and 0.42 g (1.47 mmol) of 1-octyl tosylate (Y. Liu et al. J Am. Chem. Soc. 2014, J 36, 11212-11215) was added and the reaction mixture was allowed to stir at 60 °C for 72 h. The resulting precipitate was filtered, washed with 1 mL of cold ethyl acetate and dried under vaccum to afford 0.10 g (34%) of product as a white solid.

Step 2. Prepara

7

To a 6 dram vial, 67 mg (75 μηιοΐ) of sodium tetrakis(3,5-bis(trifluoromethyl)phenyl)borate, 30 mg (38 μιηοΐ) of l,3-bis-3-(l-(l-octyl)pyridylium)thiourea tosylate and 1 mL of CH₂C1₂ were added. This mixture was stirred at room temperature under an argon atmosphere until the solid material was totally dissolved and a cloudy suspension formed. Stirring was then stopped and the solution was left undisturbed until a white solid precipitated and a clear solution formed. The reaction mixture was then filtered and concentrated under reduced pressure to afford 50 mg (60%) of product as a brown oil. ^lU NMR (500 MHz, CD₂C1₂) δ 10.14 (br s, 2H), 9.76 (s, 2H), 8.17 (d, J = 6.0 Hz, 2H), 8.16 (d, J = 8.5 Hz, 2H), 7.80 (dd, J = 6.0 and 8.5 Hz, 2H), 7.72 (s, 16H), 7.55 (s, 8H), 4.45 (t, J = 7.0 Hz, 4H), 2.02 (pentet, J = 7.0 Hz, 4H), 1.41-1.13 (m, 20H), 0.85 (t, J = 7.0 Hz, 6H).

Compound 7 could also be prepared by converting the diiodide salt. The dipyridinium diiodide salt of 7 was prepared when 1 -iodooctane was used in lieu of octyl tosylate in step 1.

Example 6. Preparation of Catalyst 8

Step 1. Preparation of l-methyl-3-(3-((lR,2S)-2-hydroxy-2,3-dihydro-lH-inden-l- yl)thioureido)pyridinium iodide

In a 6-dram vial, 50 mg (0.18 mmol) of 3-isothiocyanato-l-methylpyridinium iodide was dissolved in 2 mL of C¾CN under argon. (lR,2S)-cis-l-amino-2-indanol (27 mg, 0.18 mmol) was added and the reaction mixture was allowed to stir overnight at room temperature. A minimal amount of a 1 : 1 mixture of ethyl acetate and pentane was subsequently added (~ 3 mL) and the resulting precipitate was filtered, washed with 2 mL of pentane and dried under vacuum to afford 70 mg (90%) of product as a pale yellow solid. Step 2. Preparation of 8

8

To a 6 dram vial, 21 mg (23 μιηοΐ) of sodium tetrakis(3,5-bis(trifluoromethyl)phenyl)borate, 10 mg (23 μιηοΐ) of l-methyl-3-(3-((lR,2S)-2-hydroxy-2,3-dihydro-lH-inden-l- yl)thioureido)pyridinium iodide and 1 mL of CH₂CI₂ were added. This mixture was stirred at room temperature under an argon atmosphere until the solid material was totaBy dissolved and a cloudy suspension formed. Stirring was then stopped and the solution was left undisturbed until a white solid precipitated and a clear solution formed. The reaction mixture was then filtered and

concentrated under reduced pressure to afford 23 mg (86%) of product as a pale yellow solid.

Example 7. Preparation of Catalyst 9

Step 1. Preparation of l-(l-octyl)-3-(3-((lR,2S)-2-hydroxy-2,3-dihydro-lH-inden-l- yl)thioureido)pyridmium

In a 6-dram vial, 50 mg (0.13 mmol) of 3-isothiocyanato-l-(l-octyl)pyridinium triflate was dissolved in 2 mL of CH₂CI₂ under argon. (lR,2S)-cis-l-amino-2-indanol (19 mg, 0.13 mmol) was added and the reaction mixture was allowed to stir overnight at room temperature. A minimal amount of pentane was subsequently added (~ 3 mL) and the resulting precipitated oil was isolated and dried under vacuum to afford 50 mg (72%) of product as a brown oil. Step 2. Preparation of 9

To a 6 dram vial, 39 mg (44 μηιοΐ) of sodium tetrakis(3,5-bis(trifluoromethyl)phenyl)borate, 24 mg (44 μηιοΐ) of l-(l-octyl)-3-(3-((lR,2S)-2-hydroxy-2,3-dihydro-lH-inden-l-yl)mioureido)pyridinium triflate and 1 mL of CH2CI2 were added. This mixture was stirred at room temperature under an argon atmosphere until the solid material was totally dissolved and a cloudy suspension formed. Stirring was then stopped and the solution was left undisturbed until a white solid precipitated and a clear solution formed. The reaction mixture was then filtered and concentrated under reduced pressure to afford 45 mg (81%) of product as a brown oil.

Example 8. Preparation of Catalyst 10

Step 1. Preparation of 3-isothiocyanatoisoquinoIine (M. Sawa et al., Patent: US2013/317218 Al, 2013)

To a mixture of isoquinolin-3-amine (1.0 g, 6.9 mmol) in water (25 mL) was added CSC1₂ (0.5 mL, 7.6 mmol) slowly for a period of 5 min at 0° C, and the mixture was stirred for 2 h at room temperature. The reaction mixture was diluted with water and extracted with ethyl acetate (3 x25 mL). The combined organic layer was dried over Na₂S0₄ and concentrated under reduced pressure with a rotary evaporator. Medium pressure liquid chromatography of the residue (10 : 90 to 20 : 80 ethyl acetate/hexanes) afforded 0.83 g (64%) of product as a white solid. Step 2. Preparation of 3-isothiocyanato- -methylisoquinoIinium iodide

In a 6 dram vial, 40 mg (0.22 mmol) of 3-isothiocyanatoisoquinoline was dissolved in 1 mL of ethyl acetate and 0.23 mL (3.7 mmol) of methyl iodide was added at 40 °C under argon. The reaction mixture was allowed to stir for 72 h and the resulting precipitate was filtered, washed with 1 mL of hexane and dried under vacuum to afford 30 mg (42%) of product as a white solid.

Step 3. Preparation of l-methyl-3-(3-((lR,2S)-2-hydroxy-2,3-dihydro-lH-inden-l- yl)thioureido)isoquinolinium iodide

In a 6-dram vial, 10 mg (30 μιηοΐ) of 3-isothiocyanato-l-methylisoquinolinium iodide was dissolved in 1 mL of CH₃CN under argon. (lR,2S)-cis-l-amino-2-indanol (5 mg, 34 μηιοΐ) was added and the reaction mixture was allowed to stir overnight at room temperature. A minimal amount of a 1 : 1 mixture of ethyl acetate and pentane was subsequently added (~ 3mL) and the resulting precipitate was filtered, washed with 2 mL of pentane and dried under vacuum to afford 10 mg (67%) of product as a yellow solid.

Step 4. Preparation of 10

10

To a 6 dram vial, 19 mg (21 μιηοΐ) of sodium tetrakis(3,5-bis(trifluoromethyl)phenyl)borate, 10 mg (21 umol) of l-methyl-3-(3-((lR,2S)-2-hydroxy-2,3-dihydro-lH-inden-l- yl)thioureido)isoquinolinium iodide and 1 mL of CH2CI2 were added. This mixture was stirred at room temperature under an argon atmosphere until the solid material was totally dissolved and a cloudy suspension formed. Stirring was then stopped and the solution was left undisturbed until a white solid precipitated and a clear solution formed. The reaction mixture was then filtered and concentrated under reduced pressure to afford 22 mg (86%) of product as a yellow solid.

Example 9. Preparation of Catalyst 11

Step 1. Preparation of 3-isothio m triflate

In a 6 dram vial, 67 mg (0.36 mmol) of 3-isothiocyanatoisoquinoline was dissolved in 1 mL of ethyl acetate and 0.19 g (0.72 mmol) of 1-octyl triflate was added at room temperature under argon. The reaction mixture was allowed to stir overnight and 2 mL of pentane was added. Stirring was then stopped and the solution was left undisturbed until two organic layers were formed. The lower layer was isolated and dried under vacuum to afford 0.15 g (93%) of product as a yellow oil.

Step 2. Preparation of l-(l-octyl)-3-(3-((lR,2S)-2-hydroxy-2,3-dihydro-lH-inden-l- yI)thioureido)isoquinolinium triflate

In a 6-dram vial, 50 mg (0.11 mmol) of 3-isothiocyanato-l-(l-octyl)isoquinolinium triflate was dissolved in 2 mL of CH2CI2 under argon. (lR,2S)-cis-l-amino-2-indanol (17 mg, 0.11 mmol) was added and the reaction mixture was allowed to stir overnight at room temperature. A minimal amount of pentane was subsequently added (~ 3 mL) and the resulting precipitated oil was isolated and dried under vacuum to afford 43 mg (64%) of product as a yellow oil. Step 3. Preparation of 11

To a 6 dram vial, 22 mg (25 μηιοΐ) of sodium tetrakis(3,5-bis(trifluoromethyl)phenyl)borate, 15 mg (25 μηιοΐ) of l-(l-octyl)-3-(3-((lR,2S)-2-hydroxy-2,3-dihydro-lH-inden-l- yl)thioureido)isoquinolinium triflate and 1 mL of CH2CI2 were added. This mixture was stirred at room temperature under an argon atmosphere until the solid material was totally dissolved and a cloudy suspension formed. Stirring was then stopped and the solution was left undisturbed until a white solid precipitated and a clear solution formed. The reaction mixture was then filtered and concentrated under reduced pressure to afford 22 mg (67%) of product as a yellow oil. Example 10. Catalytic Friedel-Crafts Reaction

(1) Accelerated Friedel-Crafts Reaction

Oven dried NMR tubes were charged with 83 mM β-nitrostyrene, 250 mM of N-methylindole and 10 mol% (8.3 mM) of the indicated thiourea catalysts 1-7 in CDC1₃ at room temperature under an inert atmosphere. Reaction progress was monitored by 'H NMR using signals at 8.04 and 5.23 ppm corresponding to β-nitrostyrene and the Friedel-Crafts product, respectively. Second-order rate constants and the first half-lifes of the limiting reagent were obtained from the resulting data using the integrated rate law (i.e., ln([N-methylindole][P-nitrostyrene]o/[ -nitrostyrene][N-methylindole]o) = ¾[N-methylindole]o - [β-nitrostyrenejo), where [A]o and [A] are the initial concentrations and those at a given time, respectively) (Table 1). The catalysts of this invention correspond to rate accelerations of up to 360 with respect to Schreiner's thiourea. Equivalently, the above reaction was >96% complete in 25 minutes with compound 4 whereas it took 121 hours to obtain a 92% conversion with compound 2.

Table 1. Second-order rate constant and first half-life of the reactions catalyzed by 1-7.

(2) Enantio

Oven dried NMR tubes were charged with 83 mM β-nitrostyrene, 250 mM of N-methylindole and 10 mol% (8.3 mM) of the indicated thiourea catalysts 8-11 in CDC1₃ at -35°C under an inert atmosphere. Reaction progress was monitored by 1H NMR using signals at 8.04 and 5.23 ppm corresponding to β-nitrostyrene and the Friedel-Crafts product, respectively. Second-order rate constants and the first half-lifes of the limiting reagent and enantiomeric excess of the product were obtained from the resulting data using the integrated rate law (i.e., ln([N-methylindole][P- nitrostyrene]o/[ -nitrostyrene][N-methylindole]o) = A([N-methylindole]₀ - [P-nitrostyrene]o), where [A]o and [A] are the initial concentrations and those at a given time, respectively) (Table 2). Table 2. Second-order rate constant, first half-life enantiomeric excess of the reactions catalyzed by 8-11.

Example 11. Catalytic Aminolvsis of Styrene Oxide

A solution of 0.093 g (1.0 mmol) aniline, 0.12 g (1.0 mmol) styrene oxide and 0.1 or 1 mol% of the desired catalyst (0.001 or 0.01 mmol) in a 3 dram vial was stirred under argon at 60 °C.

Reaction progress can be monitored by TLC (6: 1 hexanes/ethyl acetate) on 250 mm 60 F-254 silica gel plates, and either at 0.5 or 2.33 hr 1 ml of CDCI₃ was added and a Ή NMR spectrum of the resulting solution was obtained.

The reaction catalyzed by compound 2 went to 39% conversion in 2.33 hours while the reaction catalyzed by compound 4 went to 93% conversion in 0.5 hours (i.e., there is ~2 orders of magnitude difference). Example 12. Catalytic Diels-Alder Reaction

Freshly prepared CDCI₃ solutions of cyclopentadiene (0.50 M), vinyl methyl ketone (0.17 M) and 1 mol% (1.7 mM) of thiourea catalyst 2, 3 or 4 were placed in dry NMR tubes at room temperature under an inert atmosphere. The progress of the Diels-Alder reaction was monitored by ^JH NMR, and second-order rate constants and the first half-life for the limiting reagent were determined as described for the Friedel-Crafts reaction.

Schreiner's thiourea (2) is a poor catalyst in that it decreases the reaction half-life from 2.2 hours (no catalyst) to 1.6 hours. In contrast, compound 3 decreases the half-life to 15 min (a 20-fold acceleration relative to Schreiner's thiourea when corrected for the uncatalyzed rate) and compound 4 lowers the half-life to 1.8 min (a 180-fold enhancement relative to Schreiner's thiourea when corrected for the uncatalyzed rate). All publications, patents, and patent documents are incorporated by reference herein, as though individually incorporated by reference. The invention has been described with reference to various specific and preferred embodiments and techniques. However, it should be understood that many variations and modifications may be made while remaining within the spirit and scope of the invention.

Claims

What is claimed is:

1. A compound of formula I:

wherein:

independently selected from H, halo, hydroxyl, nitro, cyano, trifluoromethoxy, (Ci-Ci₂)alkyl, (C₃- C₈)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, (Ci-C₆)alkoxy, (Cj-C₆)alkanoyl,

(C]-C₆)alkoxycarbonyl, and (C₂-C₆)alkanoyloxy, wherein each (Ci-C₁₂)alkyl, (C₃-C₈)cycloalkyl, (C₃- C6)cycloalkyl(Ci-C6)alkyl, (Ci-C6)alkanoyl, (Ci-C6)alkoxycarbonyl, and (C₂-C6)alkanoyloxy is optionally substituted with one or more groups independently selected from halo and wherein one or more of the nitrogen atoms in an aromatic ring is a positively charged tetravalent nitrogen associated with an anion;

B is a 6-10 membered aryl or a 5-15 membered heteroaryl comprising one or more nitrogen atoms in an aromatic ring, wherein 6-10 membered aryl and the 5-15 membered heteroaryl are optionally substituted with one or more groups independently selected from H, halo, hydroxyl, nitro, cyano, trifluoromethoxy, (Ci-C₁₂)alkyl, (C₃-Cg)cycloalkyl, (C₃-C6)cycloalkyl(C₁-C₆)alkyl, (C_\- C₆)alkoxy, (Ci-C₆)alkanoyl, (C₁-C₆)alkoxycarbonyl, and (C₂-C₆)alkanoyloxy, wherein each (Ci- Ci₂)alkyl, (C₃-C₈)cycloalkyl, (C3-C₆)cycloalkyl(C₁-C6)alkyl, (C C₆)alkanoyl, (Ci-C₆)alkoxycarbonyl, and (C₂-C6)alkanoyloxy is optionally substituted with one or more groups independently selected from halo and wherein one or more of the nitrogen atoms in an aromatic ring, if present, is optionally a positively charged tetravalent nitrogen associated with an anion.

2. The compound of claim 1 wherein A is selected from:

wherein one or more of the nitrogen atoms in an aromatic ring is further substituted with a group selected from H, (Ci-C₁₂)alkyl, (C₃-C₈)cycloalkyl, or (C3-C₆)cycloalkyl(Ci-C₆)alkyl, wherein each (Ci-C₁₂)alkyl, (C₃-C₈)cycloalkyl, and (C₃-C6)cycloalkyl(Ci-C₈)alkyl is optionally substituted with one or more groups independently selected from halo, providing one or more positively charged tetravalent nitrogen atoms associated with an anion.

3. The compound of claim 1 wherein A is selected from:

wherein the nitrogen atom in an aromatic ring is further substituted with a group selected from H, (C Ci₂)alkyl, (C₃-C₈)cycloalkyl, or (C₃-C₆)cycloalkyl(Ci-C₆)alkyl, wherein each (C,-C₁₂)alkyl, (C₃- C₈)cycloalkyl, and (C₃-C6)cycloalkyl(C₁-C₈)alkyl is optionally substituted with one or more groups independently selected from halo, providing the positively charged tetravalent nitrogen atoms associated with an anion. compound of claim 1 wherein A is selected from:

wherein the nitrogen atom in an aromatic ring is further substituted with (C₁-C₁₂)alkyl, optionally substituted with one or more groups independently selected from halo, providing the positively charged tetravalent nitrogen atoms associated with an anion.

5. The compound of claim 1 wherein A is selected from:

and is associated with an anion.

6. The compound of claim 1 wherein B is selected from:

wherein one or more of the nitrogen atoms in an aromatic ring is optionally further substituted with a group selected from H, (Ci-Ci₂)alkyl, (C₃-C₈)cycloalkyl, or (C₃-C₆)cycloalkyl(Ci-C₆)alkyl, wherein each (Ci-C₁₂)alkyl, (C₃-Cg)cycloalkyl, and (C₃-C₆)cycloalkyl(Ci-C₈)alkyl is optionally substituted with one or more groups independently selected from halo, optionally providing one or more positively charged tetravalent ring nitrogen atoms associated with an anion.

7. The compound of claim 1 wherein B is selected from:

wherein one or more of the nitrogen atoms in an aromatic ring is optionally further substituted with a group selected from H, (Ci-Ci₂)alkyl, (C3-C₈)cycloalkyl, or (C3-C6)cycloalkyl(Ci-C6)alkyl, wherein each (CrC₁₂)alkyl, (C3-C₈)cycloalkyl, and (C3-C6)cycloalkyl(C₁-C₈)alkyl is optionally substituted with one or more groups independently selected from halo, optionally providing one or more positively charged tetravalent ring nitrogen atoms associated with an anion.

8. The compound of claim 1 wherein B is selected from:

wherein the nitrogen atoms in an aromatic ring is optionally further substituted with a group selected from H, (Ci-C₁₂)alkyl, (C₃-C₈)cycloalkyl, or (C₃-C₆)cycloalkyl(Ci-C₆)alkyl, wherein each (d- Ci₂)alkyl, (C₃-C₈)cycloalkyl, and (C3-C₆)cycloalkyl(Ci-C₈)alkyl is optionally substituted with one or more groups independently selected from halo, optionally providing the positively charged tetravalent ring nitrogen atoms associated with an anion.

9. The compound of claim 1 wherein B is selected from:

wherein the nitrogen atoms in an aromatic ring is optionally further substituted with (Ci-C₁₂)alkyl, optionally substituted with one or more groups independently selected from halo, providing the positively charged tetravalent ring nitrogen atoms associated with an anion.

10. The compound of claim 1 wherein B is selected from:

11. The compound of claim 1 formula la:

(la)

wherein:

Y is ^J-R^{1 ~}X^a;

Z is CH or ⁺N-R² ^;

R¹ is H, (C₁-C₁₂)alkyl, (C₃-C₈)cycloalkyl, or (C₃-C₆)cycloalkyl(Ci-C₆)alkyl, wherein each (C,- Ci₂)alkyl, (C₃-C₈)cycloalkyl, and (C3-C₆)cycloalkyl(Ci-C₈)alkyl is optionally substituted with one or more groups independently selected from halo;

R² is H, (C_rC₁₂)alkyl, (C₃-C₈)cycloalkyl, or (C₃-C₆)cycloalkyl(Ci-C₆)alkyl, wherein each (d- C₁₂)alkyl, (C₃-C₈)cycloalkyl, and (C₃-C6)cycloalkyl(Ci-C₈)alkyl is optionally substituted with one or more groups independently selected from halo;

X^a is an anion; and

X^b is an anion.

12. The compound of claim 11 which is a compound of formula lb:

13. The compound of claim 11 which is a compound of formula Ic:

14. The compound of any one of claims 11-13 wherein Z is CH.

15. The compound of any one of claims 11-13 wherein Z is ^TN-R^{2 "}X^b.

16. The compound of any one of claims 11-15 wherein R¹ is H.

17. The compound of any one of claims 11-15 wherein R^! is (Ci-Ci₂)alkyl, optionally substituted with one or more groups independently selected from halo.

18. The compound of any one of claims 11-15 and 17 wherein R¹ is methyl or octyl.

19. The compound of any one of claims 11-15 and 17-18 wherein R¹ is methyl.

20. The compound of any one of claims 11-15 and 17-18 wherein R¹ is octyl.

21. The compound of any one of claims 11-13 and 15-20 wherein R² is H.

22. The compound of any one of claims 11-13 and 15-20 wherein R² is (C_rC₁₂)alkyl, optionally substituted with one or more groups independently selected from halo.

23. The compound of any one of claims 11-13, 15-20 and 22 wherein R² is methyl or octyl. The compound of any one of claims 11-13, 15-20 and 22-23 wherein R is methyl.

25. The compound of any one of claims 11-13, 15-20 and 22-23 wherein R² is octyl.

wherein:

Y is ⁺N-R^{1 ~}X^a;

R¹ is H, (d-C₁₂)alkyl, (C₃-C₈)cycloalkyl, or (C₃-C₆)cycloalkyl(C_rC₆)alkyl, wherein each (C Ci₂)alkyl, (C₃-C₈)cycloalkyl, and (C₃-C6)cycloalkyl(Ci-Cg)alkyl is optionally substituted with one or more groups independently selected from halo; and

X^a is an anion.

27. The compound of claim 1 which is a compound of formula Ie:

wherein:

Y is ^TSi-R^{1 ~}X^a;

R¹ is H, (C₁-Ci₂)alkyl, (C₃-C₈)cycloalkyl, or (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, wherein each (Ci-

Ci₂)alkyl, (C₃-C₈)cycloalkyl, and (C₃-C₆)cycloalkyl(Ci-C₈)alkyl is optionally substituted with one or more groups independently selected from halo; and

X^a is an anion.

28. The compound of any one of claims 26-27 wherein R¹ is H.

29. The compound of any one of claims 26-27 wherein R¹ is (Ci-Ci2)alkyl, optionally substituted with one or more groups independently selected from halo.

30. The compound of any one of claims 26-27 and 29 wherein R¹ is methyl or octyl.

31. The compound of any one of claims 26-27 and 29-30 wherein R¹ is methyl.

32. The compound of any one of claims 26-27 and 29-30 wherein R¹ is octyl.

33. The compound of any one of claims 11-32 wherein X^a is CI^", Br^", or Γ.

34. The compound of any one of claims 1 1-33 wherein X^a is Γ.

35. The compound of any one of claims 11-32 wherein X^a is ^~B(Ar)₄, wherein each Ar is independently selected from the group consisting of 6-10 membered aryl and 5-10 membered heteroaryl, wherein each 6-10 membered aryl and 5-10 membered heteroaryl is optionally substituted with one or more groups independently selected from halo, hydroxyl, nitro, cyano, trifluoromethoxy (Ci-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(Ci-C₆)alkyl, (Ci-C₆)alkoxy, (C₁-C₆)alkanoyl, (Ci-C₆)alkoxycarbonyl, and (C₂-C₆)alkanoyloxy, wherein any (Ci-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃- C₆)cycloalkyl(Ci-C₆)alkyl, (CrC₆)alkoxy, (CrC₆)alkanoyl, (C]-C₆)alkoxycarbonyl, and (C₂- C6)alkanoyloxy is optionally substituted with one or more groups independently selected from halo.

36. The compound of any one of claims 11 -32 and 35 wherein X^a is -B(3,5- bis(trifluoromethyl)phenyl)₄.

37. The compound of any one of claims 11 -25 wherein X^b is CI^", Br^", or Γ.

38. The compound of any one of claims 11-25 amd 37 wherein X^b is Γ.

39. The compound of any one of claims 11-25 wherein X^b is B(Ar)₄, wherein each Ar is independently selected from the group consisting of 6-10 membered aryl and 5-10 membered heteroaryl, wherein each 6-10 membered aryl and 5-10 membered heteroaryl is optionally substituted with one or more groups independently selected from halo, hydroxyl, nitro, cyano, trifluoromethoxy (C,-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(Ci-C₆)alkyl, (Ci-C₆)alkoxy, (C₁-C₆)alkanoyl, (Ci-C6)alkoxycarbonyl, and (C₂-C6)alkanoyloxy, wherein any (Ci-C6)alkyl, (C₃-C6)cycloalkyl, (C₃- C₆)cycloalkyl(Ci-C₆)alkyl, (Ci-C₆)alkoxy, (C₁-C₆)alkanoyl, (Ci-C₆)alkoxycarbonyl, and (C₂- C6)alkanoyloxy is optionally substituted with one or more groups independently selected from halo.

40. The compound of any one of claims 11-25 and 39 wherein X^b is

^ B(3,5-bis(trifluoromethyl)phenyl)4.

41. The compound of any one of claims 1-10 wherein the anion is CI^", Br^", or Γ.

42. The compound of any one of claims 1-10 wherein the anion is Γ.

43. The compound of any one of claims 1-10 wherein the anion is ^~B(Ar)4, wherein each Ar is independently selected from the group consisting of 6-10 membered aryl and 5-10 membered heteroaryl, wherein each 6-10 membered aryl and 5-10 membered heteroaryl is optionally substituted with one or more groups independently selected from halo, hydroxyl, nitro, cyano, trifluoromethoxy (Ci-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C,-C₆)alkyl, (Ci-C₆)alkoxy, (C C₆)alkanoyl, (Ci-C6)alkoxycarbonyl, and (C₂-C6)alkanoyloxy, wherein any (Cj-C6)alkyl, (C₃-C6)cycloalkyl, (C₃- C6)cycloalkyl(Ci-C₆)alkyl, (Ci-C₆)alkoxy, (Q-C^alkanoyl, (Ci-C₆)alkoxycarbonyl, and (C₂- C6)alkanoyloxy is optionally substituted with one or more groups independently selected from halo.

44. The compound of claim 1 that is selected from:

40

46. A method for forming a carbon-carbon bond, comprising reacting a first reactant with a second reactant in the presence of a compound as described in any one of claims 1-45 under conditions such that a carbon-carbon bond forms between the first reactant and the second reactant.

47. The method of claim 46 wherein the com ound is selected from:

4

wherein each Ar is 3,5-bis(trifluoromethyl)phenyl. The method of claim 46 wherein the compound is selected from:

4

wherein each Ar is 3,5-bis(trifluoromethyl)phenyl.

49. The method of claim 46, wherein the formed carbon-carbon bond has an enantiomeric excess greater than 50%.

50. The method of claim 46, wherein the formed carbon-carbon bond has an enantiomeric excess greater than 75%.

51. The method of claim 46, wherein the formed carbon-carbon bond has an enantiomeric excess greater than 85%.

The method of any one of claims 49-51 wherein the compound is selected from

wherein each Ar is 3,5-bis(trifluoromethyl)phenyl.

53. The method of any one of claims 46-52 wherein the compound is present in a catalytic amount.

54. The method of claim 53 wherein the compound is present in an amount of less than about 15 mole percent with respect to the first reagent.

55. The method of claim 53 wherein the compound is present in an amount of less than about 5 mole percent with respect to the first reagent.

56. The method of claim 53 wherein the compound is present in an amount of less than about 1 mole percent with respect to the first reagent.

57. The method of claim 53 wherein the compound is present in an amount of less than about 0.1 mole percent with respect to the first reagent.

58. The method of any one of claims 46-57 wherein the reacting is carried out in a solvent.

59. The method of claim 58 wherein the solvent comprises a halocarbon solvent or toluene.