A highly efficient method for the synthesis of stereochemically pure (>/=99% ee and >50/1 dr) alpha,omega-diheterofunctional reduced polypropionates has been developed. The essential features of the method are represented by the conversion of inexpensive styrene into 2-methyl-4-phenyl-1-pentanol (1) in 50% yield over two steps from styrene via Zr-catalyzed asymmetric carboalumination (ZACA) reaction in the presence of (NMI)2ZrCl2 and Pd-catalyzed vinylation of the in situ generated isoalkylalanes in the presence of Zn(OTf)2 and a catalytic amount of Pd(DPEphos)Cl2. This ZACA-Pd-catalyzed vinylation may be repeated as needed without purification. After the final ZACA reaction, oxidation with O2 provides alpha-hydroxy-omega-phenyl reduced polypropionates, which can be fully or partially purified by chromatography. After acetylation, Ru-catalyzed oxidative cleavage of the Ph ring, and reduction with BH3.THF, the second chromatographic purification provides stereoisomerically pure alpha,omega-diheterofunctional reduced polypropionates (e.g., 9 and 11) that can be further converted to key intermediates 6 and 7 for the synthesis of ionomycin (4) and borrelidin (5), respectively, by known reactions.

A Pd-catalyzed decarboxylative coupling of thiazoles and benzoxazole with various substituted benzoic acids is developed. The reaction is compatible with both electron-rich and electron-poor benzoic acids. It can also be extended to the synthesis of polyfluoro-substituted biaryls using polyfluorobenzenes as the starting materials.

An efficient and general method for the synthesis of reduced polypropionates has been developed through the application of asymmetric carboalumination of alkenes catalyzed by dichlorobis(1-neomenthylindenyl)zirconium [(NMI) 2ZrCl2]. In this investigation, attention has been focused on those reduced polypropionates that are ␣-monoheterofunctional and either -ethyl or -n-propyl. The reaction of 3-buten-1-ol with triethylaluminum (Et 3 Al) or tripropylaluminum ( n Pr3Al) in the presence of (NMI)2ZrCl2 and isobutylaluminoxane gave, after protonolysis, (R)-3-methyl-1-pentanol as well as (R)-and (S)-3-methyl-1-hexanols in 88 -92% yield in 90 -92% enantiomeric excess in one step. These 3-monomethyl-1-alkanols were then converted to two stereoisomers each of 2,4-dimethyl-1-hexanols and 2,4-dimethyl-1-heptanols via methylalumination catalyzed by (NMI) 2ZrCl2 and methylaluminoxane followed by oxidation with O 2. The four-step (or three-isolation-step) protocol provided syn-2,4-dimethyl-1-alkanols of >98% stereoisomeric purity in Ϸ50% overall yields, whereas (2S,4R)-2,4-dimethyl-1-hexanol of comparable purity was obtained in 40% overall yield. Commercial availability of (S)-2-methyl-1-butanol as a relatively inexpensive material suggested its use in the synthesis of (2S,4S)-and (2R,4S)-2,4-dimethyl-1-hexanols via a three-step protocol consisting of (i) iodination, (ii) zincation followed by Pd-catalyzed vinylation, and (iii) Zr-catalyzed methylalumination followed by oxidation with O 2. This three-step protocol is iterative and applicable to the synthesis of reduced polypropionates containing three or more branching methyl groups, rendering this method for the synthesis of reduced polypropionates generally applicable. Its synthetic utility has been demonstrated by preparing the side chain of zaragozic acid A and the C11-C20 fragment of antibiotics TMC-151 A-F. O ligo-and poly(alkene)s with methyl groups bonded to alternating carbon atoms in the main chain (compound 1 in Fig. 1) are important structural units in both polymer materials chemistry (1) and natural products chemistry. The latter includes those reduced polypropionates that contain (i) two methylbranched asymmetric carbon centers, such as zaragozic acid A (compound 2 in Fig. 1) (2), and (ii) three methyl-branched asymmetric carbon centers, such as antibiotics TMC-151 A-F (compound 3 in Fig. 1) (3). The degree of polymerization of poly(propylene) usually exceeds 10 3 . As a consequence, most of the methyl-branched carbon centers may be considered to be ''virtually achiral,'' rendering their absolute configuration practically insignificant. On the other hand, their relative stereochemistry, termed tacticity, is of crucial importance in various respects. In the cases of reduced polypropionates, where the degree of polymerization is mostly Ͻ10, typically 2-4, both absolute and relative configurations of compound 1 (Fig. 1) are critically important. It is therefore essential to construct each methyl-bearing asymmetric carbon center with the correct absolute configurati...

Copper salts, which are abundant, relatively inexpensive and possess low toxicity,h ave long been useda sv ersatile catalysts for various reactions in organic synthesis.R ecently,t he development of Cu-catalyzed or -mediated C À Hf unctionalization reactions has gaineds ignificant attention. Since the pioneering work of Daugulis on the introduction of 8-aminoquinoline and picolinic acid auxiliariesa sr emovable directing groups in transitionm etal-catalyzed C À Hb onda ctivations,t he combination of copper saltsw ith these bidentated irecting groups has emerged as an innovatives trategyf or the construction of carbon-carbon or carbon-heteroatom bonds through C À Hb ond cleavage.I na ddition to the 8-aminoquinoline and picolinamides ystems,s everal other bidentate directing groups including the 2-aminophenyloxazoline group by Yu andD ai andt he PIP systemb yS hi, have been developeda sw ell. This review intends to cover most of the recent advances on copper-catalyzed or -mediatedd irect sp 2 and sp 3 C À Hb ondf unctionalizations assisted by these bidentate directing groups.T he major achievements in this area are discussed and catalogued by the type of bonds formed (C À C, C À O, C À N, C À S, C À Pe tc.). Special attention is paid to the reaction mechanisms.S electede xamples of substrates are listed as well. In addition, apersonal outlook is given at the end.1I ntroduction 2C À CB ond Formation 3C À OB ond Formation 4C À NBond Formation 5C À SBond Formation 6C À PBondF ormation 7C À X(X= F, Cl, Br,I )BondF ormation 8I ntermolecularC À HA ctivation-Cyclization Tandem Reactions 9S ummary andOutlook

An efficient, syn-selective, all catalytic asymmetric protocol for the synthesis of alpha,omega-diheterofunctional deoxypolypropionates via Zr-catalyzed asymmetric carboalumination (ZACA reaction) was developed. The success of the method critically hinges on the one-pot conversion of unprotected allyl alcohol into TBS-protected (R)- or (S)-3-iodo-2-methyl-1-propanol (1) of 91% enantiomeric purity in 82% yield via (i) Zr-catalyzed asymmetric methylalumination, (ii) iodination, and (iii) protection with TBSCl. After zincation of 1, its Pd-catalyzed cross-coupling with various organic halides can give various organic derivatives, including 3 and 4, which can serve as key intermediates for efficient and selective syntheses of deoxypolypropionates, such as doliculide and 2,4,6,8-tetramethyldecanoic acid, and other chiral compounds, such as callystatin A. Selective monocarboalumination of 1,4-pentadiene (5 equiv) gave, after oxidation, the expected product 5, but it was 0% ee. A plausible mechanism for racemization has been proposed and experimentally supported.