Enantio- and Diastereoselective Synthesis of syn-β-Hydroxy-α-vinyl Carboxylic Esters via Reductive Aldol Reactions of Ethyl Allenecarboxylate with 10-TMS-9-Borabicyclo[3.3.2]decane and DFT Analysis of the Hydroboration Pathway

Abstract

An enantio- and diastereoselective synthesis of syn-β-hydroxy-α-vinyl carboxylate esters 3 via the reductive aldol reaction of ethyl allenecarboxylate (2) with 10-trimethylsilyl-9-borabicyclo[3.3.2]decane (1R, Soderquist’s borane) has been developed. Density functional theory calculations suggest that the allene hydroboration involves the 1,4-reduction of 2 with the chiral borane 1R, leading directly to dienolborinate Z-(O)-8a.

Allenes and computational chemistry: from bonding situations to reaction mechanisms

“…DFT calculations (M06-2X/ 6-31G(d,p)) and NMR evidence support the proposed pathway and confirm that the 10-TMS group provides large kinetic stability to intermediate Z-(O)-133 with 420 kcal mol À1 free energy barriers for 1,3-and 1,5-rearrangement pathways. 163 Finally, to end this section we briefly cite some recent computational studies on the reaction pathways followed by these boranes in the synthesis of more complex derivatives to account for experimental results. Thus, for instance, it is wellknown that chiral allyl-and crotylboron are useful reagents for the stereoselective conversion of aldehydes into homoallylic alcohols.…”

Metal‐Free Reductive Aldol Reactions

“…Roush group was also involved in developing an enantioand diastereoselective reductive aldol reaction of aldehydes and in situ formed (Z)-dienolborinates 16 for the synthesis of syn-β-hydroxy-α-vinyl carboxylic esters 17, Scheme 8. [18] The 1,4hydroboration of allenecarboxylates 14 with Soderquist borane 15 facilitated the in situ generation of (Z)-dienolborinates 16. Under the optimized conditions, allenyl esters 14 furnished reductive aldol adducts 17 in moderate to good yields and good to excellent enantio-and diastereoselectivities on a wide range of aliphatic, aromatic, and heteroaromatic aldehydes.…”

“…Roush group was also involved in developing an enantio‐ and diastereoselective reductive aldol reaction of aldehydes and in situ formed ( Z )‐dienolborinates 16 for the synthesis of syn ‐ β ‐hydroxy‐ α ‐vinyl carboxylic esters 17 , Scheme 8 [18] . The 1,4‐hydroboration of allenecarboxylates 14 with Soderquist borane 15 facilitated the in situ generation of ( Z )‐dienolborinates 16 .…”

Enantio- and diastereoselective synthesis of syn -β-hydroxy-α-alkenyl carboxamides via reductive aldol reactions of morpholine 4-methyl-2,3-pentadienoic carboxamide with diisopinocampheylborane

“…9 Specifically, we anticipated that if trisubstituted allenyl carboxamide 8 was used as the hydroboration substrate, steric interactions between the boryl diisopinocamphenyl groups and the gem dimethyl substituents at the C4 carbon would destabilize allylborane Z-10 relative to the desired enolborinate Z-(O)-9. 6 In this way, we expected that syn aldol 11 would be obtained with excellent diastereo-and enantioselectivity via aldol reactions of Z-(O)-9. The successful development of this procedure is described herein.…”

“…NMR studies of the hydroboration product mixture and density functional theory calculations of possible reaction pathways led to the conclusion that the kinetically formed enolborinate Z-(O)-5 undergoes rapid, reversible equilibration [via a 1,5-shift] with allylborane Z-6, which is the precursor of the anti diastereomer 7a. 6 In anticipation that the equilibration of enolborinate Z-(O)-5 and allylborane Z-6 could be perturbed in favor of Z-(O)-5 by using 4,4-disubstituted allenylcarboxylate derivatives as the hydroboration substrate, and in view of the exceptional enantioselectivity achieved in (Ipc) 2 BH-mediated reductive aldol reactions of a,b-unsaturated morpholine carboxamides, 8 we elected to use allenylcarboxamide 8 as the substrate for the reductive aldol reaction (Fig. 2).…”