Recent Developments in the Chiral Brønsted Acid‐catalyzed Allylboration Reaction with Polyfunctionalized Substrates

Abstract

Asymmetric allylboration has played a central role in organic synthesis ever since the pioneering work by Hoffman and Brown, having found applications in the total synthesis of many natural products. A new dawn for this 40 year-old reaction occurred with the beginning of the new century when the first catalytic asymmetric methods came into play. In less than one decade, several methodologies, able to achieve the desired homoallylic alcohols with ee ranges in the high 90s, were developed. Among them, in the present account, we will disclose our contribution to the development of the chiral binolphosphoric-derived Brønsted acid-catalyzed allylboration of aldehydes originally reported by Antilla in 2010. Our contribution to this field lies in its application to polyfunctionalized systems, both on the aldehyde and the allylboronate in question, which enables the rapid construction of molecular diversity and complexity. Parts of the work described herein have been carried out in collaboration with the groups of Profs. Akiyama and Houk.

A Versatile Bis‐Allylboron Reagent for the Stereoselective Synthesis of Chiral Diols

“…Axially chiral phosphoric acids have shown to be effective in activating allyl, allenyl, and propargyl boronates in their reactions with aldehydes . Indeed, commercially available TRIP (Table ) exhibited asymmetric induction in the allyl transfer and the best reactivity profile among all examined catalysts (see Supporting Information for reaction optimization).…”

“…After oxidative deboronation, 1,5-diol 2j was formed in 71 %yield and with ad.r. [20][21][22][23][24][25] Indeed, commercially available TRIP (Table 1) exhibited asymmetric induction in the allyl Scheme 2. We observed that addition of Sc(OTf) 3 or In(OTf) 3 led to decomposition of 1, while trifluoroacetic acid and AlCl 3 were viable catalysts.…”

“…[18,19] Axially chiral phosphoric acids have shown to be effective in activating allyl, allenyl, and propargyl boronates in their reactions with aldehydes. [20][21][22][23][24][25] Indeed, commercially available TRIP (Table 1) exhibited asymmetric induction in the allyl Scheme 2. Synthesis of (Z,Z)-hexadienyl bis-boronate 1.a )n-BuLi, TMEDA, hexane, À20 8 8Ctoroom temperature (RT);then add i-PrOBPin, Et 2 O, À78 8 8CtoRT( 61 %a fter recrystallization from pentane).…”

C-Glycosylcrotylboronates for the Synthesis of Glycomimetics

“…These data may represent matched/mismatched diastereoselectivity, wherein the influence of the ( S ) catalyst is matched to directing effects from the substrates, and the opposite bias of the ( R ) catalyst is mismatched and dominated by substrate factors . Taken together these observations suggest that these TRIP catalysts may be more effective when the intrinsic selectivity of the substrates is low and illustrate the challenges in applying stereochemical trends for relatively simple, achiral substrates to highly substituted, chiral variants, particularly polyhydroxylated frameworks with multiple, potentially ligating sites. , …”

Recent Advances in the Preparation and Application of Allylboron Species in Organic Synthesis

“…75a The exact geometry of the catalyst in the stereoinduction step has been investigated computationally by the Houk group 77 and the groups of Goodman and Pellegrinet. 78 The utility of this reaction has been thoroughly explored by the Fustero group 79 toward more complex products, including (1) relay allylation− RCM reactions for the synthesis of cyclic benzo-fused homoallylic alcohols; 80 (2) utilization of E-γ-silyl-allylBpin reagents for the synthesis of chiral allylic silanes; 81 and (3) use of aldehydes bearing tethered alkynes providing chiral ene-yne products, primed for various transition-metal-catalyzed cyclization reactions. 82 Another important advance within this realm is that of formal α-allylation reactions pioneered by the Kobayashi group.…”