A Highly Diastereoselective TiCl4-Mediated Reduction of β-Hydroxy Ketones with BH3·py — A Very Efficient and General Synthesis of syn-1,3-Diols

TiCl4-Catalyzed Hydroboration of Ketones with Ammonia Borane

“…Converting a carbonyl to a hydroxyl group is a fundamental reaction in organic chemistry, and metal-catalyzed hydroboration-hydrolysis (reduction) with dioxaborolane reagents to achieve this transformation has recently received considerable attention. , The more reactive oxo- and thia-complexes of borane [borane tetrahydrofuran (BTHF) and borane dimethyl sulfide, respectively) are routinely used for oxazaborolidine-catalyzed asymmetric reductions . In contrast, though examined for over 6 decades, carbonyl reduction with aza-complexes (amine-boranes) has not become prevalent. − The air and moisture stability of amine-boranes make them convenient to use but require longer reaction times. The disproportional cost of amine-boranes may also be a significant contributor to their underutilization .…”

“…The transition-metal-catalyzed dehydrogenation of amine-boranes, particularly ammonia borane, , was an initial concern. However, the literature revealed superstoichiometric TiCl 4 (1.2 equiv) accelerated, diastereoselective reductions of 1,3-diketones and β-hydroxy ketones with 4 equiv of pyridine-borane and diastereoselective reductions of β-alkoxy ketones and β-keto esters with amine-boranes, including t -butylamine-borane . Surprisingly, there has been no report of TiCl 4 -mediated hydroboration-hydrolysis of simple aldehydes, ketones, acids, or esters with amine-boranes.…”

Total Asymmetric Syntheses of β-Hydroxy-δ-lactones via Umpolung with Sulfur Dioxide

“…This generated the stereotriads (+)- 24 and (+)- 25 with diastereoselectivities of 6:1 and 3:1, respectively . Treatment of 24 with TiCl 4 in CH 2 Cl 2 at −78 °C afforded titanium alkoxide 26 which was reacted directly with BH 3 ·Me 2 S to give stereotetrad (+)- 27 in 90% yield. Ozonolysis of the enol ester of (+)- 27 followed by workup with Me 2 S provided lactone (+) 3 (78%).…”

Highly Stereoselective Synthesis of syn‐1,3‐Diols through a Sequential Titanium‐Mediated Aldol Reaction and LiBH4 Reduction

“…DiMare first uncovered the diastereoselective reduction of TiCl 4 ‐chelates from chiral β‐alkoxy15a and β‐hydroxy15b ketones with several borane complexes. Later, Bartoli studied in detail this transformation with BH 3 · py16a,16b and the addition of other boron reducing agents to β‐hydroxy ketone titanium alcoholates prepared by transmetallation of the corresponding lithium alcoholates with TiCl 4 16c. Remarkably, this procedure did not afford the desired 1,3‐diols but the related cyclic boronates, which had to be treated with H 2 O 2 in a basic medium to obtain the syn ‐1,3‐diols.…”