Protecting‐Group‐Free Diastereoselective CC Coupling of 1,3‐Glycols and Allyl Acetate through Site‐Selective Primary Alcohol Dehydrogenation

Abstract

The ability to discriminate between like functional groups, so as to transform organic molecules in a site-selective or chemoselective manner, [1] precludes the requirement of protecting groups and, hence, carries the potential to dramatically enhance synthetic efficiency. [2] Though an exceptionally daunting challenge, systematic efforts toward catalytic methods for the site-selective transformation of polyfunctional molecules have begun to emerge. For example, the groups of Miller [3] and Taylor [4] report catalytic methods for the site-selective manipulation of diols and higher polyols. Site-selective metal-catalyzed cross-couplings have been catalogued. [5] Further, in what is perhaps the most formidable theatre for site selectivity, impressive advances in catalytic methods for CÀH functionalization have been achieved, as illustrated in the seminal work of Barton, [6b] Murai and Kakiuchi, [6a] and in more recent studies by the groups of Davies, [6c] Sanford, [6d] Yu, [6e] Daugulis, [6f] Baran, [6g] and others.

Chemoselective conversion of biologically sourced polyols into chiral synthons

“…The number of products that could be accessed from ring-opened or ring-closed sugars by controlling the positional selectivity of a deoxygenation process is significant, and such products would have the properties of a fine or specialty chemical. The possibility of synthesizing multiple high-value materials by controlling the deoxygenation of a small number of base carbohydrate feedstocks is appealing but poorly supported by the literature, although the chemoselective functionalization of complex polyols is an emerging field of considerable importance [13][14][15][16][17][18] .…”

Catalyst‐Directed Diastereo‐ and Site‐Selectivity in Successive Nucleophilic and Electrophilic Allylations of Chiral 1,3‐Diols: Protecting‐Group‐Free Synthesis of Substituted Pyrans

“…[6h] While use of an isolable, single component catalyst offers certain advantages, for example, allowing reactions to be conducted at lower temperatures, [6f] generation of the catalyst in situ from commercial components enables rapid evaluation of structurally diverse complexes. To identify an efficient in situ generated catalyst for the diastereo- and site-selectivity in the C -allylation chiral 1,3-diols, the commercially available malic acid derived diol 1a was exposed to allyl acetate in the presence of [Ir(cod)Cl] 2 , various 4-substituted-3-nitro-benzoic acids, and assorted axially chiral chelating phosphine ligands.…”

“…Most importantly, the diastereoselectivities observed in connection with the present protocol for in situ catalyst generation are uniformly better than the diastereoselectivities previously observed using related chromatographically purified catalysts. [6h] …”

“…[6,7] Remarkably, the cyclometalated π-allyliridium C,O -benzoate catalysts used in such alcohol C -allylations display a pronounced kinetic preference for primary alcohol dehydrogenation, [8,9] enabling site-selective allylation of unprotected diols and triols with high levels of catalyst-directed diastereoselectivity. [6h,10] …”

Alkynes as Electrophilic or Nucleophilic Allylmetal Precursors in Transition‐Metal Catalysis

“…To date, this mode of reactivity has only been observed in hydrogen transfer-mediated carbonyl allylations of alcohol proelectrophiles. [2j,33] In 2009, following reports by Krische on related allylative processes involving allenes, [6] dienes [8] and allylic carboxylates, [34] Obora and Ishii reported the first examples of alkyne-alcohol C-C coupling to form products of carbonyl allylation. [20a,b] Specifically, using the iridium catalyst derived from [Ir(OH)(cod)] 2 and P( n Oct) 3 primary alcohols react with aryl propynes to provide racemic products of (α-aryl)allylation with complete levels of anti -diastereoselectivity.…”