Organoboranes. 53. A high-field variable-temperature proton and boron-11 NMR study of the effects of solvent and structure on reactivity in allylboration

Abstract

In order to evaluate the importance of solvent, temperature, and structural effects on the rates of allylboration, the reactions of benzaldehyde with structurally representative allylboron reagents were examined under a variety of conditions by high-field variable-temperature and UB NMR spectroscopy. In general, polar solvents which are poorly coordinating enhance the rate of allylboration while solvents capable of relatively stronger coordination retard the rate. -Trisubstituted aldehydes undergo allylboration relatively slowly compared to the less substituted aldehydes. Among cyclic allylboronates, the 1,3,2-dioxaborolane derivatives, 14-17, undergo allylboration more rapidly compared to the B-allyl-l,3,2-dioxaborinane (11). In contrast to the cyclic allylboronates 14-16 which exhibit resistance to allylboration at -78 °C, the B-allyl-1,3,2-dioxabenzoborole (17) undergoes exceptionally rapid allylboration (100%, <30 s, -50 °C). While the reactivity of B-allyl-1,3,2-oxazaborolidines 18 and 19 is comparable to that of B-allyl-1,3,2-dioxaborolane ( 16), the B-allyl-3-(p-tolylsulfonyl)-l,3,2-oxazaborolidine (20) undergoes allylboration remarkably rapidly, even at -78 °C. The acyclic allylboronates 21-25 undergo, without exception, more rapid allylboration at 0 °C compared to allyl-l,3,2-dioxaborinane (11). Moreover, the B-allylbis(benzyloxy)borane ( 24) and allylboronic acid (25) undergo allylborations relatively rapidly, even at -50 °C. While the tartramide reagent 26 undergoes allylboration at -78 °C relatively slowly, the tartrate ester derivative 3 (Roush's reagent) undergoes effortless allylboration under identical conditions. These individual variations in the rates of allylboration of the boronate derivatives can be rationalized essentially in terms of the relative availability of the lone pairs of electrons on the atoms attached to boron. The B-allyldiisopinocampheylborane ( 7) and B-allyldi(4-isocaranyl)borane ( 8) undergo instantaneous allylborations at -78 °C and have thus proven to be among the most reactive of the allylboron reagents presently known.The importance of allyl-and crotylboron reagents in acyclic stereoselection has been amply demonstrated by many research groups over the past few years. Required to support applications in natural product syntheses,3 efforts are constantly made toward the development of new reagents that can generate contiguous diastereomeric relationships with exceptional selectivity.4 Interestingly, although many reagents 1-9 have gained prominence,22 a systematic understanding of the factors controlling reactivity in allylboration, such as the solvent, temperature, the structures of the aldehyde, and that of the chiral auxiliary, is still lacking. Further, it is often very difficult to ascertain from the published reports just how reactive a particular reagent is and at what temperature the allylboration might actually be occurring.5 Indeed, we be-(1) Visiting Research Scientist on Grant GM-10937 from the National Institutes of Health.

Allylation of Aldehyde and Imine Substrates with in situ Generated Allylboronates — A Simple Route to Enantioenriched Homoallyl Alcohols.

“…On the other hand, we were not able to stabilize the palladium(0) catalyst in these solvents by addition of phosphanes [e.g. PPh 3 , P(OPh) 3 ] or activated alkenes (e.g. maleic anhydride and COD), as these additives strongly inhibited the catalytic process.…”

“…In a typical reaction the diboronate 1, the allylacetate 2, the appropriate electrophile (3 or 4) and catalytic amounts of Pd 2 (dba) 3 [dba = (dibenzylidene)acetone] were mixed in DMSO and after the allotted reaction time (Table 1) the corresponding product (5 or 6) was isolated. Using 1a as diboronate reagent the typical reaction temperature was room temperature or 40°C, however the crotyl substrate (Entry 2) required a somewhat higher reaction temperature (60°C).…”

“…Other strongly coordinating ligands, such as halide salts also retarded or completely inhibited the catalytic formation of the transient allylboranes. Therefore, employment of Pd 2 (dba) 3 as catalyst source and DMSO as solvent or co-solvent (vide infra) seems to be indispensable for the catalytic generation of allylboronates from diboronate precursors.…”

“…The corresponding electrophile 3-4 (0.3 mmol) and Pd 2 (dba) 3 (0.009 mmol) were dissolved in DMSO (3 mL) followed by addition of the allylic substrate 2a-g (0.36 mmol). This reaction mixture was stirred for 10 min at room temperature under Ar.…”

“…regio-and stereodefined products. [1][2][3][4][5] Furthermore, tartrate based chiral allylboronates react with aldehydes with good to high level of enantioselectivity. [4,6,7] Although, the parent allylboronate and its alkyl-substituted analogs are easily available reagents, the limited access to properly functionalized and/or chiral allylboronates often limit the synthetic scope of the allylation reactions.…”