Recent advances in efficient and selective synthesis of di-, tri-, and tetrasubstituted alkenes via Pd-catalyzed alkenylation-carbonyl olefination synergy.
Although generally considered competitive, the alkenylation and carbonyl olefination routes to alkenes are also complementary. In this Account, we focus on these approaches for the synthesis of regio- and stereodefined di- and trisubstituted alkenes and a few examples of tetrasubstituted alkenes. We also discuss the subset of regio- and stereodefined dienes and oligoenes that are conjugated. Pd-catalyzed cross-coupling using alkenyl metals containing Zn, Al, Zr, and B (Negishi coupling and Suzuki coupling) or alkenyl halides and related alkenyl electrophiles provides a method of alkenylation with the widest applicability and predictability, with high stereo- and regioselectivity. The requisite alkenyl metals or alkenyl electrophiles are most commonly prepared through highly selective alkyne addition reactions including (i) conventional polar additions, (ii) hydrometalation, (iii) carbometalation, (iv) halometalation, and (v) other heteroatom-metal additions. Although much more limited in applicability, the Heck alkenylation offers an operationally simpler, viable alternative when it is highly selective and satisfactory. A wide variety of carbonyl olefination reactions, especially the Wittig olefination and its modifications represented by the E-selective HWE olefination and the Z-selective Still-Gennari olefination, collectively offer the major alternative to the Pd-catalyzed alkenylation. However, the carbonyl olefination method fundamentally suffers from more limited stereochemical options and generally lower stereoselectivity levels than the Pd-catalyzed alkenylation. In a number of cases, however, very high (>98%) stereoselectivity levels have been attained in the syntheses of both E and Z isomers. The complementarity of the alkenylation and carbonyl olefination routes provide synthetic chemists with valuable options. While the alkenylation involves formation of a C-C single bond to a CC bond, the carbonyl olefination converts a CO bond to a CC bond. When a precursor to the desired alkene is readily available as an aldehyde, the carbonyl olefination is generally the more convenient of the two. This is a particularly important factor in many cases where the desired alkene contains an allylic asymmetric carbon center, since alpha-chiral aldehydes can be prepared by a variety of known asymmetric methods and readily converted to allylically chiral alkenes via carbonyl olefination. On the other hand, a homoallylically carbon-branched asymmetric center can be readily installed by either Pd-catalyzed isoalkyl-alkenyl coupling or Zr-catalyzed asymmetric carboalumination (ZACA reaction) of 1,4-dienes. In short, it takes all kinds to make alkenes, just as it takes all kinds to make the world.
Negishi
Ei-ichi
E
H. C. Brown Laboratories of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907-2084, USA. negishi@purdue.edu
Huang
Zhihong
Z
Wang
Guangwei
G
Mohan
Swathi
S
Wang
Chao
C
Hattori
Hatsuhiko
H
D000475:Alkenes / Q000138:chemical synthesis* / Q000737:chemistry; D002255:Carbonic Acid / Q000737:chemistry*; D002384:Catalysis; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry; D018942:Macrolides / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D011753:Pyrones / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry
D000475:Alkenes; D005231:Fatty Acids, Unsaturated; D007783:Lactones; D018942:Macrolides; D011753:Pyrones; D013844:Thiazoles; C519727:archazolid A; C519728:archazolid B; C421091:callystatin A; C451488:mycolactone A; C429103:ratjadone; D002255:Carbonic Acid; D010165:Palladium