Enantioselective Syntheses of 1,4-Pentadien-3-yl Carbinols via Brønsted Acid Catalysis

Abstract

An asymmetric addition of substituted 1,3-pentadienylboronates to aldehydes via Brønsted acid catalysis is reported. Under the developed conditions, a variety of synthetically useful 1,4-pentadien-3-yl carbinols were obtained in good yields with high enantioselectivities in the presence of a catalytic amount of a chiral phosphoric acid.

Cobalt-Catalyzed Diastereo- and Enantioselective Reductive Allyl Additions to Aldehydes with Allylic Alcohol Derivatives via Allyl Radical Intermediates

“…Incorporation of allyl groups bearing a 1,4-diene unit will produce homoallylic alcohols, which widely exist in natural products and are building blocks that are commonly used in the synthesis of biologically active molecules and small-molecule probes . Few examples of catalytic enantioselective allyl addition to generate homoallylic alcohols containing a 1,4-diene moiety have been reported, albeit with significant limitation of scope of allyls . We applied our reaction conditions to the allylic carbonates substituted with various alkenyl groups (Scheme ).…”

“…Although recently, catalytic enantioselective addition of allyl–Cr intermediates bearing tertiary and quaternary centers have been reported with limited scope of aldehydes and allyl groups, different catalysts, reaction conditions, and large excess amounts of additives were required . Moreover, enantioselective addition of allyl groups bearing a 1,4-diene moiety remained scarce with significant limitation on the allyl diversity. , In addition, different approaches for the introduction of allyl groups with various substitution patterns and functional groups normally required different reaction conditions, catalysts, and allyl precursors, many of which are air-sensitive, difficult to handle, and tedious to synthesize. Our goal is to develop a general catalytic platform for site-, diastereo-, and enantioselective addition of allyl groups in high diversity derived from common allyl precursors that are easily prepared and robust to a wide range of aldehydes promoted by a single inexpensive Co catalyst without the need of large excess amounts of other additives and costly cryogenic conditions, harnessing the unique nucleophilic reactivity of ambiphilic allyl–Co complexes.…”

An overview of the applications of chiral phosphoric acid organocatalysts in enantioselective additions to CO and CN bonds

“…One year later, Chen's group described the nucleophilic addition of 1,3-pentadienylboronates 412 (R 2 = CR = CHR; R 3 = Me or H; R 4 , R 5 , R 6 = H) to aldehydes 86 , using the same CPA-catalyst, obtaining 1,4-pentadien-3-yl carbinols 414 in excellent yields and enantiomeric excesses (71–98%, 91–99% ee) (Scheme 122b). 329 The reaction tolerates the use of many different aromatic, aliphatic and conjugated aldehydes 86 in combination with substituted 1,3-pentadienylboronates 412 holding or not different methyl substituents (in R 2 and R 3 ), obtaining compounds 414 as single anti diastereoisomers. Following an identical procedure, the Z -selective allylation of aldehydes 86 with α-vinyl allylboronates 412 (R 2 , R 3 , R 4 , R 6 = H; R 5 = CH = CH 2 ), affords homoallylic alcohols 415 in good yields (62–98%), high Z -selectivities (15 : 1 to >30 : 1 Z: E ) and excellent enantioselectivities (90–97% ee) (Scheme 122c).…”

Cobalt-Catalyzed Diastereo- and Enantioselective Allyl Addition to Aldehydes and α-Ketoesters through Allylic C–H Functionalization

“…However, very few enantioselective methods have been developed for addition of a 1,4-diene unit to carbonyls and the diversity of 1,4-diene groups that can be introduced is very limited. 55,56 We next applied the reaction conditions to the transformations of 1,4-dienes ( Figure 4). Unexpectedly, we found that a trisubstituted alkene moiety is required for high e ciency and stereoselectivity.…”