Asymmetric Synthesis of Isomerically Pure Allenyl Boranes from Alkynyl Boranes through a 1,2‐Insertion–1,3‐Borotropic Rearrangement

Abstract

Very recently, we described a variety of new 10-trimethylsilyl-9-borabicyclo[3.3.2]decane (10-TMS-9-BBD) reagents for the asymmetric allyl-, crotyl-, allenyl-, and propargylboration of aldehydes.[1] Prepared through adaptations of known organoborane transformations, these rigid and robust trialkyl borane systems are exceptionally stable and selective. Moreover, the related 10-Ph-9-BBD reagents, which are quite effective for the related addition reactions to ketones and ketimines, can also be prepared readily. [2] Simple Grignard procedures can be used to prepare many of these reagents, including the B-alkynyl 10-TMS-9-BBDs (2), the asymmetric Michael addition of which to N-acyl aldimines provides nonracemic N-propargyl amides.[3] On the basis of modeling studies with 2, we envisaged the highly stereoselective insertion of TMSCHN 2 into the alkynyl BÀC bond of 2 to give 4 via 3 (Scheme 1). An antiperiplanar 1,2-alkynyl migration (Matteson-type homologation) [4a] followed by a sterically driven suprafacial 1,3-borotropic rearrangement were expected to proceed with a minimum of TMS-TMS repulsions and ultimately convert the propargyl borane 4 into the novel chiral allenyl borane 1. [1c, 2a, 4b] The thermally stable, optically pure alkynyl boranes 2 (a: R = Me; b: R = (CH 2 ) 4 Cl; c: R = c-Pr; c-Pr = cyclopropyl) are readily prepared in either enantiomeric form through the reaction of the corresponding alkynyl Grignard reagents with the pseudoephedrine complexes 6 (96-99 %). At room temperature, TMSCHN 2 reacts cleanly with 2 with the evolution of nitrogen to form 1 ( 11 B NMR: d = 78 ppm) in 3 h. We view this process as occurring through the reversible addition of TMSCHN 2 to the least hindered side of 2, followed by the insertion of CHTMS into 2 with inversion. The chiral a-borylallenes 1 are then produced in enantiomerically and diastereomerically pure form in essentially quantitative yield by a suprafacial 1,3-borotropic rearrangement (Scheme 1).Asymmetric allenylboration [1b, 2c, 5] is a highly useful organoborane transformation. Compound 1 was tested as an asymmetric allenylboration reagent with representative aldehydes (Scheme 2). The addition was rapid at À78 8C (3 h), and the intermediate borinic esters 5 produced were either oxidized or converted into the pseudoephedrine complexes 6 for recycling back to 2 by the Grignard methodology. The syn b-TMS homopropargylic alcohols 7 were isolated in 80-96 % yield with d.r. 99:1 and 94-99 % ee (Table 1). This process is more enantioselective than allenylboration with the parent B-allenyl system (93-95 % ee).[1b] The enhanced enantioselectivity can be attributed to the additional a substituent Scheme 1. The preparation of 1 from 2 through insertion-borotropic rearrangement. TMS = trimethylsilyl.Scheme 2. Asymmetric allenylboration with 1.

Enantioselective Synthesis of (Z)- and (E)-2-Methyl-1,5-anti-Pentenediols via an Allene Hydroboration–Double-Allylboration Reaction Sequence

“…As anticipated in Figure 2, the kinetic hydroboration adduct ( Z )- 2 can undergo reversible 1,3-borotropic shifts 11 at elevated temperatures to give ( E )- γ –boryl-allylborane ( E )- 2 . 4b We were intrigued by the possible stereochemical outcome of double allylboration of aldehydes with bifunctional allylboranes such as ( E )- 2 .…”

Enantioselective Syntheses of syn- and anti-β-Hydroxyallylsilanes Via Allene Hydroboration-Aldehyde Allylboration Reactions

“…6c However, compared to the methods available to prepare anti - β -hydroxyallylsilanes, stereoselective synthesis of the diastereomeric syn - β -hydroxyallylsilane isomers, and especially enantioselective syntheses of the syn isomers, 5e, 7f largely remains an unsolved problem due to the facile isomerization of ( Z )- and ( E )- γ -silylallylmetal reagents. 4, 9, 10 Therefore, development of a stereocontrolled method for synthesis of chiral, nonracemic ( Z )- γ -silylallylmetal reagents and the corresponding syn - β -hydroxyallylsilanes via enantioselective aldehyde allylation remains an important goal. Accordingly, we have developed and report herein a simple, one step, diastereo- and enantioselective synthesis of syn - β -hydroxyallylsilanes via a highly stereoselective allene hydroboration-aldehyde allylboration reaction sequence.…”

“…Most ( Z )-crotylboranes are configurationally unstable at temperatures above −60 °C. 9b, 11 Allylboranes incorporating the Soderquist borane (10-TMS-9-borabicyclo[3.3.2]decanyl) auxiliary constitute the only general exception. 10 …”

“…As shown in Scheme 1, the kinetic adduct 9 Z can isomerize to the more stable allylborane 9 E through a reversible 1,3-boratropic shift 9 at temperatures above −40 °C, presumably via the intermediacy of 10 . Subsequent allylboration of aldehydes with 9E should allow access to the diastereomeric anti - β -hydroxyallylsilanes 8 (which we have previously demonstrated by an alternative method).…”

Reprint of: Enantiodivergent hydroboration reactions of a racemic allenylsilane with diisopinocampheylborane and Curtin–Hammett controlled double asymmetric crotylboration reactions of (S)-E-α-phenyldimethylsilyl(ddiisopinocampheyl)-crotylborane

“…Although it is expected that ( S )- E - 5 can equilibrate with ( S )- E - 15 via a reversible 1,3-boratropic shift. 16 1 H NMR studies on the hydroboration of single enantiomer allenylsilanes ( P )- 4 and ( M )- 4 indicate that the amount of ( S )- E - 15 in the equilibrium mixture is negligible (not observed). Hence, these data suggest that: (1) the rate of the mismatched double asymmetric crotylboration of aldehydes 20a – c with ( S )- E - 15 (Scheme 7) is much faster than the rate of crotylboration with ( S )- E - 5 ; and (2) the rate of equilibration between ( S )- E - 5 and ( S )- E - 15 is much faster than the rates of the mismatched double asymmetric crotylboration of aldehydes 20 with these crotylboranes.…”