Asymmetric Organocatalytic Homologation: Access to Diverse Chiral Trifluoromethyl Organoboron Species

Abstract

A broad range of aliphatic, aromatic, and heterocyclic boronic acids were successfully homologated using trifluorodiazoethane in the presence of BINOL derivatives to provide the corresponding chiral trifluoromethyl containing boronic acid derivatives in high yields and excellent enantioselectivity. The in situ conversion of the chiral transient boronic acids to the corresponding alcohols or β‐CF3 carboxylates are also demonstrated.

Three-Component Approach to Densely Functionalized Trifluoromethyl Allenols by Asymmetric Organocatalysis

“…This reactive chiral boron ester 12 forms an ate complex with trifluoromethyl diazomethane 2 , which undergoes 1,2-borotropic rearrangement to give chiral α-CF 3 propargylboronate 13 . Similar reactions for synthesis of α-CF 3 organoboronates have been reported in the literature. ,,, Isolation of propargylboronate 8 (Figure b) indicates that the reactions proceeded via intermediate 14 . According to our results (Table , entries 1, 4, 5), the C–X bond length of the 3,3′-substituents of BINOL is particularly important for the stereoinduction, and application of the iodo derivative 4 gives the highest selectivity for the reaction.…”

“…The product was air sensitive, and therefore the boron was protected by diamino-naphthalene to give 8 , which could be purified by silica gel chromatography. Propargyl boronate 8 is much less stable , than its alkyl, benzyl, or allyl analogs. Nevertheless, we determined the structure and optical purity (85% ee) of 8 .…”

“…Nevertheless, we determined the structure and optical purity (85% ee) of 8 . The absolute configuration of 8 was tentatively assigned to be S based on the X-ray structures obtained for the allyl, benzyl, and methyl-cyclopropyl analogs, which all have S configuration. Unfortunately, the low stability and resistance to crystallization prevented the X-ray analysis of 8 .…”

“…The presence of the BINOL moiety and the CF 3 substituent probably increases the Lewis acidity of the boron. The reaction with ketones, similarly to aldehydes, is supposed to proceed via a Zimmerman–Traxler-type TS. ,, Based on previous studies the enantioselectivity is determined in the 12 → 14 process, while ,, the diastereoselectivity is controlled by the chirality transfer in the allenylboration step 14 → 15 . Finally, ethanolysis of 15 leads to formation of the boric ester of product 5 ( 16 ) and regeneration of the catalyst.…”

“…The coupling of 6 with various alkenyl boronate substrates 1 (R 1 = 4-CF 3 C 6 H 4 , C 4 H 9 ) and ketones (R 2 = 4-NO 2 C 6 H 4 , 4-CF 3 C 6 H 4 , 3-BrC 6 H 4 , R 3 = CH 3 , CH 2 Br) proceeded with high selectivity (95–98% ee) formation of a single diastereomer for allenols 7a – d . Stabilized diazo-carbonyl, -ester, or -cyano precursors (instead of 2 or 6 ) cannot be used in asymmetric homologation, as with these types of diazo compounds and organoboronates the Hooz reaction − takes place, which occurs without formation of a C–B stereocenter.…”