Direct Synthesis of B-Allyl and B-Allenyldiisopinocampheylborane Reagents Using Allyl or Propargyl Halides and Indium Metal Under Barbier-Type Conditions

Abstract

We report the first one-pot process for the asymmetric addition of allyl, methallyl, and propargyl groups to aldehydes and ketones using B-chlorodiisopinocampheylborane ((d)DIP-Cl) and indium metal. Under Barbier-type conditions, indium metal was used to generate allyl- and allenylindium intermediates, and subsequent reaction with (d)DIP-Cl successfully promoted the transfer of these groups to boron forming the corresponding chiral borane reagents. The newly formed borane reagents were reacted with aldehydes and ketones to produce the corresponding alcohol products in high yields and up to excellent enantioselectivity (98% ee). This method produced excellent enantioenriched secondary homoallylic alcohols from the allylation and methallylation of benzaldehyde. Using this method, the methallylation and cinnamylation of ketones afforded the highest enantioselectivities, while the propargylation of both aldehydes and ketones provided low enantiomeric excesses. In addition, this procedure provided the first synthesis of B-allenyldiisopinocampheylborane, which was characterized by (1)H and (11)B NMR spectroscopy. This is the first example of the direct synthesis of allylboranes that contained substitutions from the corresponding allyl bromide and indium, thereby expanding the utility of the DIP-Cl reagent. Hence, a general and straightforward route to these chiral organoborane reagents in one-pot has been developed along with the asymmetric Barbier-type allylation and propargylation of aldehyde and ketone substrates using these chiral organoborane reagents in subsequent coupling reactions.

Importance of a 4-Alkyl Substituent for Activity in the Englerin Series

“…We were able to favor the desired homoallylic alcohol 11 by employing the B-allyldiisopinocampheylborane reagent prepared according to Singaram. 20 Treatment with carbonyl diimidazole then gave the metathesis substrate.…”

“…Regioselective opening of the epoxide ring gave the 1,2-diol 9 and oxidation gave the expected aldehyde 10 . We were able to favor the desired homoallylic alcohol 11 by employing the B-allyldiisopinocampheylborane reagent prepared according to Singaram . Treatment with carbonyl diimidazole then gave the metathesis substrate.…”

Total Synthesis of Laingolide B Stereoisomers and Assignment of Absolute Configuration

“…In conclusion, we have completed the first total synthesis of two stereoisomers of laingolide B, (−)-(2 R ,9 S )- 6a and (+)-(2 S ,9 S )- 6b , in a 12-step longest linear sequence from the known ( S )- 12 in 9–10% overall yields. The RCM–alkene isomerization strategy has been demonstrated as a powerful tool in the construction of this unique 15-membered N -Me-enamide-containing macrolide.…”

“…Two ( Z )-trisubstituted silylated alkenyl iodides rac - 10 and 15 were prepared from rac - 12 and homopropargylic alcohol, respectively, via Pd-catalyzed silylstannylation , using n -Bu 3 Sn–TMS to form the silylated alkenylstannanes rac - 13 and 14 followed by selective tin–iodine exchange (Scheme ). The alkyl borane 11 was readily prepared from the chiral 4-acyloxazolidinone 16 via methylation to give 17 (92%) followed by hydroboration of 17 with dimeric 9-BBN.…”

“…Similarly, 9 was coupled with rac - 10 and 15 in THF to afford the products 24b and 24c , respectively, in 77% and 79% yields. The chiral ( Z )-silylated alkenyl iodide ( S )- 10 was prepared from ( S )- 12 in 74% overall yield as described for rac - 10 in Scheme . Silylation of ( S )- 10 gave the TBS ether ( S )- 23a (97%); the latter was coupled with 9 to give 24d in 77% yield.…”