Cross‐Metathesis/Iridium(I)‐catalyzed Allylic Etherification Strategy: (Iterative) Catalytic Asymmetric Synthesis of syn‐ and anti‐1,2‐Diols

Abstract

1,2-Diol functional groups are common structures in many biologically active natural products [1] and "privileged" chiral catalysts/ligands. [2] Furthermore, 1,2-diols can serve as valuable synthetic precursors for the construction of a wide variety of other useful structures. 1,2-Diols can appear in many different forms depending on their protection state (diprotected, monoprotected, or free diol), as well as their absolute and relative stereochemistry (syn or anti). Thus, an ideal synthetic method/strategy for 1,2-diols would be one that can a) furnish any of the aforementioned 1,2-diol forms and b) control their absolute and relative stereochemistry by using a pair of enantiomeric ligands/catalysts, but such methodology is not currently available.Despite tremendous methodological advancements, literature inspection surprisingly revealed that almost all prior asymmetric methods for the synthesis of 1,2-diols focused on controlling relative stereochemistry of 1,2-diols, thus giving either syn-or anti-1,2-diols, and employed chiral reagents and auxiliaries for stereochemical control. [3][4][5][6][7][8] In addition, they often suffered from a narrow substrate scope, low yields, and low stereoselectivities. To our knowledge, the only catalytic asymmetric method that met the above two criteria was recently reported by the McQuade group, who employed the copper-catalyzed asymmetric allylic boronation/cross-metathesis (AAB/CM) strategy. [9] Although highly selective formation of differentiated syn-and anti-1,2-diols could be achieved by using a pair of enantiomeric ligands, the strategy required two extra steps for the in situ oxidation of the boronate product of the AAB reaction and the subsequent alcohol protection, and the AAB reaction did not occur with a TBS protecting group, thus considerably limiting the generality and practicality of the strategy.In recent years, iridium(I)-catalyzed allylic substitution reactions have emerged as a powerful tool for the enantioselective introduction of carbon-carbon and carbon-heteroatom bonds. [10] A distinct feature of iridium(I)-catalyzed allylic substitution reactions is the formation of chiral branched allylation products from achiral linear allyl sub-strates, which complements the more traditional palladiumcatalyzed allylic substitution reactions which typically give rise to linear allylation products. [11] Iridium-catalyzed allylic etherification reactions have been shown to generate a wide range of protected and free chiral allylic alcohols in high yields at synthetically useful levels of stereoselectivity [Eq. (1); PG = protecting group]. [12] We recently demonstrated that iridium(I)-catalyzed decarboxylative allylic etherification exhibited much broader substrate scope and higher reaction yield than the corresponding intermolecular version, and that stereoselection in iridium(I)-catalyzed diastereoselective decarboxylative allylic etherification was controlled by the ligands/catalysts used [Eq.(2); PMP = p-methoxyphenyl]. [13] Based on these results, we envision...

Enantioselective Functionalization of Allylic C–H Bonds Following a Strategy of Functionalization and Diversification

“…The N -allylamine product was subjected to the previously reported sequence of hydroboration, intramolecular Suzuki-Miyaura cross-coupling, and alkylation to provide (-)-angustureine. 8a The relative configuration of the product and iridium catalyst shows that the allylic substitution step of the functionalization sequence occurs with the same stereoselectivity as previously reported substitutions of allylic carbonates. 7c,15 Previously reported mechanistic studies from our group on iridium catalyzed allylic substitution reactions 7d,16 have shown that the reaction occurs by a highly diastereoselective oxidative addition of an allylic benzoate to an iridium complex 1 , followed by attack of the nucleophile onto the allyl ligand from the side opposite to the metal for all of the nucleophiles in the current study.…”

“…Because the iridium catalyst controls the configuration of the new stereocenter, 7e,8 the allylic substitution provides a method to control the diastereoselectivity of the amination of chiral, non-racemic alkenes. For example, the chiral alkene ( ee > 99%) containing a MOM-protected alcohol (MOM=methoxy methyl) reacted to form the substitution product 3p in 57% yield with 18:1 diastereoselectivity.…”

“…For example, both diastereomers of a silyl protected enantioenriched amino alcohol ( 7a and 7b ) were prepared using catalyst 1 and the enantiomer of 1 respectively, with dr values similar to the er values of the reactions of achiral alkenes. 8b,8c The chiral alkene prepared from malonate addition was further functionalized with the aromatic amine in high diastereoselectivity ( 7d ). A chiral 1,3 diamine containing different substituents at nitrogen also formed with high diastereoselectivity ( 7e ).…”

“…7 In this reaction many types of carbon, nitrogen, oxygen, and sulfur nucleophiles react with an allylic electrophile to form products in which the configuration of the new stereo-center is controlled by the catalyst, rather than existing stereogenic centers in the substrate. 7e,8 …”

Facile and Highly Diastereoselective Synthesis of syn‐ and cis‐1,2‐Diol Derivatives from Protected α‐Hydroxy Ketones

“…Prominent are organocatalyzed aldol reactions of protected α‐hydroxy ketones and aldehydes11a,21 or diastereodivergent, enantioselective glycolate aldol reactions 22 . syn ‐ or anti ‐Alkenyl‐1,2‐diols can be accessed by nucleophilic addition of 3‐oxy‐substituted allylic organometallic reagents to various aldehydes with moderate to good selectivity,23 whereas anti ‐alkenyl‐1,2‐diols have been prepared through Ni‐catalyzed reductive coupling of alkynes and α‐oxy aldehydes24 or by iterative sequences of olefin cross‐metathesis and iridium(I)‐catalyzed decarboxylative allylic etherifications 25…”