Diisopropyl 2-Crotyl-1,3,2-dioxaborolane-4,5-dicarboxylate1,2

(1) L-(R,R)-tartrate (E)-crotyl

[99745-86-5]  · C14H23BO6  · Diisopropyl 2-Crotyl-1,3,2-dioxaborolane-4,5-dicarboxylate  · (MW 298.14) D-(S,S), (Z)

[99687-40-8] L-(R,R), (Z)

[106357-20-4] (2) D-(S,S), (E)


(reagents for the asymmetric crotylboration of aldehydes to produce either syn or anti b-methylhomoallylic alcohols)2

Physical Data: bp 80 °C/0.1 mmHg.

Solubility: sol toluene, THF, ether, or CH2Cl2.

Analysis of Reagent Purity: 11B NMR, data for (E)-crotyl: (d 34.8, C6D6);2b the purity of the reagent is best determined by capillary GC;2b solutions of the reagent can be standardized using cyclohexanecarbaldehyde.2b

Preparative Method: prepared by treatment of (E)- or (Z)-crotylpotassium with Triisopropyl Borate followed by acidic extractive workup and direct esterification with diisopropyl tartrate (DIPT) (eqs 1 and 2).2

Handling, Storage, and Precautions: typically the reagents are handled as solutions in toluene (0.5-1M) and transferred by syringe under an inert atmosphere; stored neat or as a solution in toluene over 4Å molecular sieves under an argon atmosphere in a refrigerator (-20 °C), the reagent is stable for many months. In the presence of water, (1) rapidly hydrolyzes to achiral crotylboronic acid, the presence of which leads to reduced enantioselectivity in reactions with aldehydes.

Reactions with Achiral Aldehydes.

The tartrate ester modified (E)- and (Z)-crotylboronates undergo rapid additions to aldehydes at -78 °C. The enantioselectivities obtained for aliphatic linear or a-monobranched aldehydes range from 72 to 91% ee.2 When cyclohexanecarbaldehyde is treated with the (E)-crotylboronate reagent at -95 °C in toluene, the homoallylic alcohol is obtained in 98% yield and 91% ee (eq 3). The (Z)-crotylboronate reagent gives slightly lower selectivity (83% ee, eq 4). The anti:syn/syn:anti ratios obtained are also excellent for this reagent (typically greater than 98:2 and 2:98 for (1) and (2), respectively).

As with the corresponding allylboronate, the enantioselectivity of reactions with b-alkoxy and conjugated aldehydes are lower (55-74% ee). In the case of benzaldehyde (91%, 66% ee), selectivity can be improved by the use of the derived chromium tricarbonyl complex. The homoallylic alcohol is obtained after oxidative decomplexation in high yield and 92% enantiomeric purity (eq 5).3

Reactions with Chiral Aldehydes.

Addition of the (E)- or (Z)-crotylboronate reagent to optically active b-alkoxy-a-methylpropionaldehydes gives the corresponding polypropionate structures with good to excellent diastereoselection (eqs 6 and 7).4 Three of the four stereochemical triads can be prepared in high yield with useful levels of selectivity. The all-syn stereoisomer of eq 7 is best prepared using other methods, such as the crotyltin methodology developed by Keck and co-workers.5 The polypropionate structures with 1,3-anti relationships between branching methyl groups are prepared with excellent diastereoselection (via matched double asymmetric reactions). Those with a 1,3-syn relationship are more difficult to prepare. The relative diastereoselectivity of the reaction of a-methyl chiral aldehydes with (E)- and (Z)-crotylboronates can be predicted by use of the gauche pentane model.6

Both (E)- and (Z)-crotylboronates have been used in several applications in natural product synthesis.4b,7 One application of both the allylboronate and (E)-crotylboronate reagents is found in the synthesis of the C(19)-C(29) segment of rifamycin S. The desired stereochemistry at C(25)-C(26) of the rifamycin ansa chain is set with excellent stereocontrol (>95:5) and high yield (87%) (eq 8).4b,7a

The (E)- and (Z)-crotylboronates provide selectivity in the best cases comparable to that obtained with other crotylboration procedures. Combining ease of preparation, stability, and selectivity the tartrate-modified (E)- and (Z)-crotylboronates are highly useful propionate enolate equivalents.

Related Reagents.

B-Allyldiisocaranylborane; B-Crotyldiisopinocampheylborane; (R,R)-2,5-Dimethylborolane.

1. Roush, W. R. COS 1991, 2, 1.
2. (a) Roush, W. R.; Halterman, R. L. JACS 1986, 108, 294. (b) Roush, W. R.; Ando, K.; Powers, D. B.; Palkowitz, A. D.; Halterman, R. L. JACS 1990, 112, 6339; JACS 1991, 114, 5133.
3. Roush, W. R.; Park, J. C. JOC 1990, 55, 1143.
4. (a) Roush, W. R.; Palkowitz, A. D.; Palmer, M. A. J. JOC 1987, 52, 316. (b) Roush, W. R.; Palkowitz, A. D.; Ando, K. JACS 1990, 112, 6348.
5. Keck, G. E.; Abbott, D. E. TL 1984, 25, 1883.
6. (a) Evans, D. A.; Nelson, J. V.; Taber, T. R. Top. Stereochem. 1982, 13, 1. (b) Roush, W. R. JOC 1991, 56, 4151.
7. (a) Roush, W. R.; Palkowitz, A. D. JACS 1987, 109, 953. (b) Danishefsky, S. J.; Armistead, D. M.; Wincott, F. E.; Selnick, H. G.; Hungate, R. JACS 1987, 109, 8117. (c) Coe, J. W.; Roush, W. R. JOC 1989, 54, 915. (d) Roush, W. R.; Palkowitz, A. D. JOC 1989, 54, 3009. (e) Tatsuta, K.; Ishiyama, T.; Tajima, S.; Koguchi, Y.; Gunji, H. TL 1990, 31, 709. (f) Akita, H.; Yamada, H.; Matsukura, H.; Nakata, T.; Oishi, T. TL 1990, 31, 1735. (g) White, J. D.; Johnson, A. T. JOC 1990, 55, 5938. (h) Fisher, M. J.; Myers, C. D.; Joglar, J.; Chen, S.-H.; Danishefsky, S. J. JOC 1991, 56, 5826. (i) Roush, W. R.; Bannister, T. D. TL 1992, 33, 3587. (j) Roush, W. R.; Brown, B. B. JACS 1993, 115, 2268. (k) White, J. D.; Porter, W. J.; Tiller, T. SL 1993, 535.

David J. Madar

Indiana University, Bloomington, IN, USA

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