In one aspect, phosphine compounds comprising three adamantyl moieties (PAd.sub.3) and associated synthetic routes are described herein. Each adamantyl moiety may be the same or different. For example, each adamantyl moiety (Ad) attached to the phosphorus atom can be independently selected from the group consisting of adamantane, diamantane, triamantane and derivatives thereof. Transition metal complexes comprising PAd.sub.3 ligands are also provided for catalytic synthesis including catalytic cross-coupling reactions.

The invention discloses a mixed Ni(II) complex containing bisoxazoline-derived nitrogen heterocyclic carbene ligand and phosphite ligand and application thereof; the chemical formula of the mixed Ni(II) complex is Ni(NHC)[P(OR).sub.3]X.sub.2, wherein R is ethyl or isopropyl, X is bromine or chlorine, and NHC is a bisoxazoline-derived nitrogen heterocyclic carbene ligand. In the presence of magnesium shavings, the mixed Ni(II) complex containing bisoxazoline-derived nitrogen heterocyclic carbene ligand and phosphite ligand of the present invention can catalyze low-activity chlorinated aromatic hydrocarbons and fluorinated aromatic hydrocarbons with chlorinated benzyl compounds, respectively, reductive cross-coupling reaction at a single temperature, generating a diarylmethane compound in one step, providing a new method for the synthesis of diarylmethane compounds.

Provided herein is a process for synthesis of intermediates for ipatasertib related to large scale manufacture of (R)-5-methyl-4-(piperazin-1-yl)-5,6-dihydro-7H-cyclopenta[d]pyrimidin-7-one.

In one aspect, phosphine compounds comprising three adamantyl moieties (PAd.sub.3) and associated synthetic routes are described herein. Each adamantyl moiety may be the same or different. For example, each adamantyl moiety (Ad) attached to the phosphorus atom can be independently selected from the group consisting of adamantane, diamantane, triamantane and derivatives thereof. Transition metal complexes comprising PAd.sub.3 ligands are also provided for catalytic synthesis including catalytic cross-coupling reactions.

A method includes: providing a mixture including at least one alkyl tosylate and a Grignard reagent; and reacting the at least one alkyl tosylate with the Grignard reagent in a C—C coupling reaction mechanism to form a branched aliphatic alcohol.

The invention provides compounds of general structure I: (Ar.sup.1—Ar.sup.2—Ar.sup.3-E-P(=D)R.sub.2-).sub.nM.sub.mX.sub.nL.sub.n″. In this structure: •Ar.sup.1, Ar.sup.2 and Ar.sup.3 are aromatic groups wherein: —Ar.sup.1 and Ar.sup.3 are in a 1,3 relationship on Ar.sup.2, —each of Ar.sup.1, Ar.sup.2 and Ar.sup.3 optionally comprises one or more ring substituents of formula YR′.sub.r wherein each Y independently is absent or is O, S, B, N or Si and each R′ is independently H, halogen, alkyl, cycloalkyl, aryl or heteroaryl and r is 1, 2 or 3, where r is 1 if Y is absent or is O or S, 2 if Y is B or N and 3 if Y is Si, —Ar.sup.1, Ar.sup.2 and Ar.sup.3 are each independently carbocyclic or heterocyclic and each is independently monocyclic, bicyclic or polycyclic and each ring of each of Ar.sup.1, Ar.sup.2 and Ar.sup.3 independently has 5, 6 or 7 ring atoms; •E is absent or is selected from the group consisting of O, S, NR″, SiR″.sub.2, AsR″.sub.2 and CR″.sub.2; •M is a complexing metal; •X is selected from the group consisting of H, F, Br, CI, I, OTf, dba (dibenzylidene acetone), OC(═O)CF.sub.3 and OAc; •L is selected from the group consisting of PR″.sub.2, NR″.sub.2, OR″, SR″, SiR″.sub.3, AsR″.sub.3, alkene, alkyne, aryl and heteroaryl, each of said alkene, alkyne, aryl and heteroaryl being optionally substituted, for example with one or more halogens and/or with one or more R groups as defined herein; •each R is independently alkyl, cycloalkyl, heterocyclyl, heterocycloalkyl, aryl or -, heteroaryl; •D is absent or is ═S or —O or —Z-linker-Z—, where each Z independently is O or NH or N-alkyl and linker is an alkyl chain of 2-5 carbon atoms in length; •each R″ is independently H, alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl, each other than H being optionally substituted, or R″.sub.2 is —Z-linker-Z— as defined above; and •m is 0 or 1 or 2; wherein if m is 0, n is 1, n′ and n″ are 0 and -- is absent; and if m is 1 or 2, n is 1 or 2 and n′ and n″ are integers such that the coordination sphere of M is filled, and D is absent.

In one aspect, phosphine compounds comprising three adamantyl moieties (PAd.sub.3) and associated synthetic routes are described herein. Each adamantyl moiety may be the same or different. For example, each adamantyl moiety (Ad) attached to the phosphorus atom can be independently selected from the group consisting of adamantane, diamantane, triamantane and derivatives thereof. Transition metal complexes comprising PAd.sub.3 ligands are also provided for catalytic synthesis including catalytic cross-coupling reactions.

The invention discloses a mixed Ni(II) complex containing bisoxazoline-derived nitrogen heterocyclic carbene ligand and phosphite ligand and application thereof; the chemical formula of the mixed Ni(II) complex is Ni(NHC)[P(OR).sub.3]X.sub.2, wherein R is ethyl or isopropyl, X is bromine or chlorine, and NHC is a bisoxazoline-derived nitrogen heterocyclic carbene ligand. In the presence of magnesium shavings, the mixed Ni(II) complex containing bisoxazoline-derived nitrogen heterocyclic carbene ligand and phosphite ligand of the present invention can catalyze low-activity chlorinated aromatic hydrocarbons and fluorinated aromatic hydrocarbons with chlorinated benzyl compounds, respectively, reductive cross-coupling reaction at a single temperature, generating a diarylmethane compound in one step, providing a new method for the synthesis of diarylmethane compounds.

A method includes: providing a mixture including at least one alkyl tosylate and a Grignard reagent; and reacting the at least one alkyl tosylate with the Grignard reagent in a C—C coupling reaction mechanism to form a branched aliphatic alcohol.

In one aspect, phosphine compounds comprising three adamantyl moieties (PAd.sub.3) and associated synthetic routes are described herein. Each adamantyl moiety may be the same or different. For example, each adamantyl moiety (Ad) attached to the phosphorus atom can be independently selected from the group consisting of adamantane, diamantane, triamantane and derivatives thereof. Transition metal complexes comprising PAd.sub.3 ligands are also provided for catalytic synthesis including catalytic cross-coupling reactions.