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Chiral Phosphoric Acid Catalysts for Asymmetric Synthesis

BINOL- and SPINOL Derived Phosphates Serve as Powerful Instruments for Enantioselective Organic Transformations

Binaphthyl (BINOL) and dispiroindane (SPIROL) core structured phosphoric acids represent a very important class of asymmetric organocatalysts that can efficiently catalyze various organic reactions under mild and environmentally friendly conditions. [1]  Catalytic activity of the chiral phosphates is very much dependent on the acidity (pKa) and geometry of the phosphates.

Chiral phosphates mainly act as Brønsted acid catalysts performing enantioselective protonation.[2,3] However, since Brønsted acid lacks the acidity, it is sometimes used as a pre-catalyst and transformed, in situ, into a Lewis acid to catalyze a reaction.[2]  To increase the application range of the organocatalysts, limitations related to the molecular structure are overcome by fine-tuning of BINOL and SPIROL cores mainly at 3,3' and 7,7' positions respectively by different organic radicals. The acidity is adjusted by the introduction of strong electron acceptor groups (e.g. bistriflimide derivatives) in to the phosphoric acid group.[3]

Although they are frequently used as pure organocatalysts, chiral phosphates are often implemented in  combination with transition metal complexes.  In this case metal interacts with phosphate anion to form transitional RO2POOMn+ complex (where RO2 is the chiral group) and acts as a Lewis acid catalyst.[1, 4]  In addition, the oxygen-double bonded to the phosphorus is able to donate lone electron pair and acts as a Lewis base.

The basic BINOL-derived phosphoric acids are binaphthyl-2,2'-diyl hydrogenphosphates (15-0052 (R); 15-0053 (S)).  In addition to these, Strem Chemicals offers other organocatalysts with a wide variety of bulky substituents at 3,3' position, which are summarized on Fig. 1.

 1.1                                             1.2

R=H

15-0052

(R)

 

R=H

15-1371

(R)

R=H

15-0053

(S)

 

R=H

15-1370

(S)

R=SiPh3

15-0340

(R)

 

R=Ph(3,5-CF3)2

15-1376

(R)

R=SiPh3

15-0341

(S)

 

R=Ph(3,5-CF3)2

15-1377

(S)

R=Ph(3,5-CF3)2

15-1366

(R)

 

R=Ph(3,5-Me)2

15-1373

(R)

R=Ph(3,5-CF3)2

15-1367

(S)

 

R=Ph(3,5-Me)2

15-1374

(S)

R=Ph(3,5-Me)2

15-1368

(R)

 

R=2-naphtyl

15-1378

(R)

R=Ph(3,5-Me)2

15-1369

(S)

 

R=2-naphtyl

15-1379

(S)

R=Ph(2,4,6-iPr)3

15-1381

(R)

 

R=1-naphtyl

15-1383

(R)

R=Ph(2,4,6-iPr)3

15-1382

(S)

 

R=1-naphtyl

15-1384

(S)

R=Ph

15-1386

(R)

 

R=Ph(2,4,6-iPr)3

15-1394

(S)

R=Ph

15-1387

(S)

 

R=Ph(2,4,6-iPr)3

15-1395

(R)

R=1-naphtyl

15-1388

(R)

 

R=Ph

15-1396

(R)

R=1-naphtyl

15-1389

(S)

 

R=Ph

15-1397

(S)

R=2-naphtyl

15-1390

(R)

 

 

 

 

R=2-naphtyl

15-1391

(S)

 

 

 

 

R=Ph(4=CF3)

15-1392

(R)

 

 

 

 

R=Ph(4=CF3)

15-1393

(S)

 

 

 

 

Figure 1. BINOL-derived phosphoric acids

 

BINOL-derived phosphoric acids are capable of catalyzing a wide range of reactions including reductive amination, Pictet-Spengler Reactions, aza-Diels–Alder addition reactions, cascade reactions and many others.[1,2]

Although BINOL-phosphate related catalytic processes have been intensively studied during the last 10 years, application of SPIROL-derived phosphoric acids are relatively new and less explored, therefore research is more prospective. A majority of the research groups studied the (R)- stereoisomer of the spiro-catalysts.  Strem also offers (R)-enantiomer of chiral spiro phosphoric acid for enantioselective synthesis[5-6] (Fig. 2.).

15-0542

Figure 2. Chiral spiro phosphoric acid. Catalog # 15-0542

 

There are many examples of the SPIROL-phosphate catalyzed reactions such as: asymmetric amination reaction, which is co-catalyzed by Rhodium(II) trifluoroacetate dimer ([Ru2(TFA)4] 45-1960)[7]; asymmetric cyclization of quinone monoimides with olefins[8]; asymmetric arylation of diazo compounds with aniline derivatives which is also co-catalyzed by an achiral dirhodium complex[9]; Friedel-Crafts reactions[10, 11]; catalytic asymmetric Fischer indolization[12, 13]; asymmetric protonation of silyl ketene imines[14]; enantioselective N–H insertion reaction [15] and others[16]..

Transformations catalyzed by BINOL and SPIROL phosphates are all efficient with high yields and excellent enantioselectivities.  For a more detailed description of each catalytic process please review the corresponding technical notes on our website.  A broader review can also be found in the comprehensive contributions [1,2], which describe all aspects of the asymmetric synthesis performed by chiral phosphates in great detail.

 

References:

  1.    Chem. Rev., 2014, 114, 9047−9153
  2.    Chem. Rev., 2015, 115, 9277-9306
  3.    J. Am. Che,m. Soc. 2006, 128, 9626-9627
  4.    Coord. Chem. Rev., 2016, 308, 131-190
  5.    J. Org. Chem., 2011, 76, 4125
  6.    Angew. Chem. Int. Ed., 2011, 50, 11483
  7.    Chem. Commun., 2014, 50, 14639-14642
  8.    Chem. Commun., 2016, 52, 2968-2971
  9.    J. Am. Chem. Soc., 2015, 137, 8700-8703
  10.    J. Org. Chem., 2010, 75, 8677-8680
  11.    J. Org. Chem., 2011, 76, 4125-4131
  12.    Angew. Chem. Int. Ed., 2013, 52, 9486-9490
  13.    Angew. Chem. Int. Ed., 2014, 53, 5202-5205
  14.    J. Am. Chem. Soc., 2013, 135, 2100-2103
  15.    Angew. Chem. Int. Ed., 2014, 53, 3913-3916
  16.    J. Am. Chem. Soc., 2016, 138, 16561

 

Products mentioned in this blog and related products:

15-0052: (R)-(-)-1,1'-Binaphthyl-2,2'-diyl hydrogenphosphate, min. 98% [39648-67-4]

15-0053: (S)-(+)-1,1'-Binaphthyl-2,2'-diyl hydrogenphosphate, min. 98% [35193-64-7]

15-0542: (11aR)-3,7-Bis(3,5-dimethylphenyl)-10,11,12,13-tetrahydro-5-hydroxy-5-oxide-diindeno[7,1-de:1',7'-fg][1,3,2]dioxaphosphocin, min. 98% [1297613-75-2]

45-1960: Rhodium(II) trifluoroacetate dimer, min. 95% [31126-95-1]

 

For additional resources please visit the links below:

Chiral Phosphoric Acids Literature Sheet

Chiral Phosphoric Acids Product Listing

 

 

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