(R)- and (S)-5-trimethylsilyl-2-cyclohexenone: a versatile chiral source for the synthesis of optically active cyclohexanone derivatives

Asaoka, Morio; Shima, Kunihisa; Takei, Hisashi

doi:10.1016/s0040-4039(00)96809-6

Cited by 60 publications

(15 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These conclusions are supported by the use of diastereomeric product ratios as “fingerprints” to track the involvement of the CIP and SIP species. Reactions of phenylthio(3-methyl)benzyllithium ( 7 ), which is similar to 3 in its ion pair behavior, with 5-trimethylsilyl-2-cyclohexen-1-one ( 8 ) were performed in Et 2 O with incremental amounts of THF added, followed by incremental amounts of HMPA. The total amount of 1,4 addition and the diastereomer distribution within the 1,4 products are shown in Figure .…”

mentioning

confidence: 60%

Regioselectivity of Addition of Organolithium Reagents to Enones: The Role of HMPA

Reich

Sikorski

1998

J. Org. Chem.

View full text Add to dashboard Cite

mentioning

confidence: 60%

Regioselectivity of Addition of Organolithium Reagents to Enones: The Role of HMPA

Reich

Sikorski

1998

J. Org. Chem.

View full text Add to dashboard Cite

“…To our surprise a more bulky isopropyl group ( 1 b ) led to a slight decrease in the selectivity ( s =39; Table 1, entry 10), and substrate 1 c containing a phenyl group at the 5‐position also gave a lower selectivity ( s =19; Table 1, entry 11) than 1 a . Resolution of the synthetically important 5‐trimethylsilyl‐2‐cyclohexenone ( 1 d ) was also successful, providing 86 % ee at 56 % conversion ( s =14, Table 1, entry 12) 3a, 16b, 17…”

Section: Methodsmentioning

confidence: 99%

Highly Enantioselective Copper-Phosphoramidite Catalyzed Kinetic Resolution of Chiral 2-Cyclohexenones

et al. 2001

View full text Add to dashboard Cite

Chiral 2-cyclohexenones are attractive building blocks for the synthesis of a variety of natural products. A limited number of naturally occurring optically active cyclohexenones such as pulegone, piperitone, and carvone are cheap, readily available, and widely used for this purpose. [1] The development of routes to other optically active 2-cyclohexenones includes the preparation of nonnatural cyclohexenones from naturally occurring ones; for example, 4-methyland 5-methylcyclohexenone can be derived from pulegone and carvone. [2] Recently the groups of Corey and Sato introduced elegant methods for the synthesis of enantiomerically pure 2-cyclohexenones which can easily be converted into a variety of other chiral 2-cyclohexenones. [3] Although both methods are widely applicable they consist of multistep syntheses to obtain the desired 2-cyclohexenone synthons. On the other hand a variety of racemic 2-cyclohexenones is readily accessible. This encouraged us to develop a general method towards optically active 2-cyclohexenones by kinetic resolution of racemic 2-cyclohexenones based on the copper ± phosphoramidite catalyzed 1,4-addition to enones [Eq. (1)]. [4] It was anticipated that the high enantioselectivity obtained with these catalysts in the 1,4-addition of diethylzinc to 2-cyclohexenone (b 98 % ee, [Eq. (1)]), [4] combined with the high trans-diastereoselectivity generally found in the addition of organometallic reagents to, for example, 5-alkyl-substituted 2-cyclohexenones, [5] should provide high selectivity in the kinetic resolution of such compounds [Eq. (2)]. [6,7] To check the viability of this new approach we tested the ligands L1 ± L5 in the kinetic resolution of racemic 5-substituted 2-cyclohexenones 1 a ± d under the conditions typical for the asymmetric 1,4-addition as shown in Scheme 1. By using [Cu(OTf) 2 ] (1 mol %), (S,R,R)-L1 (2 mol %), and Et 2 Zn (0.8 equiv) in toluene at À 40 8C for the resolution of (AE)-5methyl-2-cyclohexenone (1 a) on a 1 mmol scale, an ee of 88 % Scheme 1. Kinetic resolution of racemic 5-substituted 2-cyclohexenones 1 a ± d under the conditions typical for asymmetric 1,4-addition.was reached at 48 % conversion indicating a selectivity (s) of 120 (Table 1, entry 1). [8±10] Accordingly after 20 min 53 % conversion had taken place and unreacted 1 a with 99 % ee was found. This high selectivity makes the resolution synthetically applicable. [11] Based on the expected trans-diastereoselectivity and the fact that the 1,4-addition of Et 2 Zn to 2-cyclohexenone in the presence of L1 produces (S)-3-ethylcyclohexanone we predicted the unreacted enantiomer to be (R)-1 a which turned out to be correct. [4d, 5, 12] A good correlation was observed between the results with the ligands L1 ± L5 in the 1,4-addition of diethylzinc to 2-cyclohexenone and the results in the kinetic resolution (Table 1, entries 1 ± 9). The most successful ligands in the 1,4addition, namely (S,R,R)-L1, (S,R)-and (S,S)-L2 (Table 1, entries 3 and 4), and (S,R,R)-L3 (Table 1, entry 5), also give the highest ...

show abstract

“…The easily accessible naturally occurring 2-cyclohexenones used for this purpose are, however, restricted to only a few such as carvone and pulegone . Therefore, considerable efforts have been made to develop an efficient method to prepare chiral 2-cyclohexenones − as well as to introduce new 2-cyclohexenone chiral building blocks …”

Section: Introductionmentioning

confidence: 99%

Synthesis of Optically Active 5-(tert-Butyldimethylsiloxy)-2-cyclohexenone and Its 6-Substituted Derivatives as Useful Chiral Building Blocks for the Synthesis of Cyclohexane Rings. Syntheses of Carvone, Penienone, and Penihydrone

et al. 1999

View full text Add to dashboard Cite

Optically active 5-(tert-butyldimethylsiloxy)-2-cyclohexenone (1) and its 6-substituted derivatives 2a,b were synthesized from the readily available optically active ethyl 3-(tert-butyldimethylsiloxy)-5-hexenoate (4), where the Ti(II)-mediated intramolecular nucleophilic acyl substitution reaction and the FeCl3-mediated ring expansion reaction of a 1-hydroxybicyclo[3.1.0]hexane are the key reactions. The enone 1 reacted with higher-order cyanocuprates with excellent diastereoselectivity to afford the trans-addition products, trans- 13, in excellent yields. The reaction of 1 with lower-order cyanocuprates proceeded with moderate to excellent syn-selectivity to afford cis- 13. Treatment of trans- and cis- 13 with DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) or catalyst p-TSA (p-toluenesulfonic acid) resulted in a β-elimination reaction to furnish the corresponding optically active 5-substituted-2-cyclohexenones 14. The 1,4-addition reaction of 2a and 2b with organocyanocuprates followed by treatment of the resulting 20 with DBU provided the 2,5-disubstituted-2-cyclohexenones 19 with excellent ee. The conversion of 14 into the 3,5-disubstituted-2-cyclohexenone 22 has also been carried out via 1,2-addition of alkyllithium onto the carbonyl group and the following oxidation with PCC (pyridinium chlorochromate). Similarly, the conversion of 19 into 2,3,5-trisubstituted-2-cyclohexenones 24 has been carried out. A highly efficient, first total synthesis of penienone 25 and penihydrone 26 has been accomplished. Thus, the 1,4-addition reaction of 1 with the (E,E)-1,3-heptadienyl cyanocuprate and consecutive trap of the resulting copper enolate with formaldehyde gave 28, which upon treatment with DBU or Pyr·HF yielded 25 and 26, respectively. An efficient synthesis of both enantiomers of carvone starting from (S)- 20ab has been also accomplished.

show abstract

(R)- and (S)-5-trimethylsilyl-2-cyclohexenone: a versatile chiral source for the synthesis of optically active cyclohexanone derivatives

Cited by 60 publications

References 7 publications

Regioselectivity of Addition of Organolithium Reagents to Enones: The Role of HMPA

Regioselectivity of Addition of Organolithium Reagents to Enones: The Role of HMPA

Highly Enantioselective Copper-Phosphoramidite Catalyzed Kinetic Resolution of Chiral 2-Cyclohexenones

Synthesis of Optically Active 5-(tert-Butyldimethylsiloxy)-2-cyclohexenone and Its 6-Substituted Derivatives as Useful Chiral Building Blocks for the Synthesis of Cyclohexane Rings. Syntheses of Carvone, Penienone, and Penihydrone

Contact Info

Product

Resources

About