[76347-09-6]  · C6H13BO2  · Crotyldimethoxyborane  · (MW 127.98) (Z)


(stereoselective aldehyde crotylborating agents;1 precursors of other crotylboronic esters via hydrolysis and esterification with diols2)

Alternate Name: dimethyl crotylboronate.

Physical Data: the title reagents are generated and used in situ.3 The analogous diisopropyl (E)- and (Z)-crotylboronates have been isolated and characterized:4 diisopropyl (E)-crotylboronate, bp 49-60 °C/3-4 mmHg; diisopropyl (Z)-crotylboronate, bp 40-50 °C/2-4 mmHg.5

Solubility: crotylboronic esters are soluble in common organic solvents (Et2O, CH2Cl2, toluene, etc.). The title reagents are moisture sensitive and hydrolyze to the crotylboronic acids when exposed to water; they undergo transesterification reactions with alcohols.

Form Supplied in: not commercially available.

Analysis of Reagent Purity: in general, allylboronic esters may be purified by distillation and characterized by 1H, 13C, or 11B NMR.3a,6,7 Chemical and isomeric purity has been determined in many cases by capillary GC analysis.3a,7

Preparative Methods: the title reagents have been generated and used in situ (see below).

Handling, Storage, and Precautions: allylboronates that are purified by distillation may be stored, often for months, in a refrigerator either neat or as a solution in an inert solvent such as CH2Cl2 or toluene.7 Allylboronic esters are moisture sensitive and are readily hydrolyzed by water to the allylboronic acids (which readily undergo aerial oxidation). The most stable allylboronic esters are the pinacol esters; however, these are also the least reactive members of the group.1,8 In general, the reactions of allylboronic esters with carbonyl compounds should be performed in a well ventilated hood in a dry solvent under an inert atmosphere.

Reagent Preparation.

The title reagents are prepared in situ by metalation of (E)- or (Z)-2-butene with n-Butyllithium-Potassium t-Butoxide followed by treatment of the resulting (E)- or (Z)-crotylpotassiums with Fluorodimethoxyborane Diethyl Etherate diethyl etherate ((MeO)2BF.Et2O; typically two equiv; (eqs 1 and 2)).3 Erratic yields and stereoselectivity are reported for reactions of the dimethyl (E)- or (Z)-crotylboronates (1) and (2) with aldehydes if two equiv of (MeO)2BF.Et2O are not used; the second equiv is added to trap t-BuOLi which is generated in the metalation step.3c Related procedures have been used to synthesize a range of substituted allylboronic esters, including g-alkoxyallylboronates (3) and (4).9

Acid hydrolysis of THF solutions of (1) and (2) provides the corresponding (E)- and (Z)-crotylboronic acids (note: air sensitive) that are readily esterified when treated with diols in the presence of a drying agent (typically MgSO4). Eqs 3 and 4 illustrate the application of this procedure for the synthesis of pinacol crotylboronates (5) and (6).2a The procedure was fully optimized for the synthesis of the tartrate ester modified crotylboronates (7) and (8) (eqs 5 and 6).7 It was found that the yield and isomeric purity of the crotylboronates decreased as the scale increased when (MeO)2BF was used to functionalize the crotylpotassium intermediates. For example, on scales up to 100 mmol using (MeO)2BF as the borylating agent, (7) and (8) were obtained in 70-88% yield following distillation with isomeric purities of 96-97% for (7) and 97-98% for (8). However, the yields of (7) and (8) fell to 14-35% on scales larger than 200 mmol with isomeric purity of 94-96% and 92-95% for (7) and (8), respectively. It is believed that these problems result from competitive formation of tricrotylborane.7 A far superior procedure involves use of Triisopropyl Borate as the electrophilic borylating agent.10 The (i-PrO)3B procedure has been performed on 100-400 mmol scales with excellent results: 70-75% yields of (7) (&egt;98% E) and (8) (&egt;99% Z) have been obtained consistently.7 Kabalka has adopted this procedure for the preparation of the diisopropyl crotylboronates (9) and (10) (43-46% yield following distillation).4,5

Diastereoselective Reactions with Aldehydes.

(E)- and (Z)-crotylboronates react with aldehydes generally with excellent diastereoselectivity.1,6 As shown in eqs 7 and 8, the reaction of propanal and (E)-crotylboronate (1) provides the anti homoallyl alcohol with 96:4 selectivity, while the reaction with the (Z)-crotylboronate (2) gives the syn diastereomer with 97% selectivity.3c The stereochemical outcome of the reactions of allylboronates and aldehydes is best rationalized by way of cyclic, chair-like transition states (11).1a Numerous examples of reactions of substituted allylboronates and aldehydes have been documented in the literature, and in most cases the diastereoselectivity parallels the isomeric purity of the reagent.1a Chiral reagents (7) and (8) can be used to perform these reactions enantioselectively (65-90% ee for most aldehydes).7

Diastereoselective Reactions with a-Hydroxy Ketones and a-Oxocarboxylic Acids.

The addition reaction of allylboronates to ketones is very slow; for example, the reactions of ketones of (E)- and (Z)-pentenylboronates requires 4-5 day reaction times at elevated pressure.11 However, Kabalka has demonstrated that the diisopropyl crotylboronates (9) and (10) react readily with a-hydroxy ketones (eq 9).4 The reaction presumably involves transesterification of the a-hydroxy ketone with the reagent and then crotyl transfer by way of the chair-like transition state (12). Allylboronates also react with a-oxocarboxylic acids, presumably by way of a similar transition state.12

Related Reagents.

B-Allyldiisocaranylborane; B-Crotyldiisopinocampheylborane; Crotyltrichlorosilane; Crotyltrifluorosilane; Diisopropyl 2-Allyl-1,3,2-dioxaborolane-4,5-dicarboxylate; Triethylammonium Bis(catecholato)allylsiliconate.

1. (a) Roush, W. R. COS 1991, 2, 1. (b) Yamamoto, Y.; Asao, N. CR 1993, 93, 2207.
2. (a) Roush, W. R.; Adam, M. A.; Walts, A. E.; Harris, D. J. JACS 1986, 108, 3422. (b) Roush, W. R.; Halterman, R. L. JACS 1986, 108, 294.
3. (a) Rauchschwalbe, G.; Schlosser, M. HCA 1975, 58, 1094. (b) Schlosser, M.; Fujita, K. AG(E) 1982, 21, 309. (c) Fujita, K.; Schlosser, M. HCA 1982, 65, 1258.
4. Wang, Z.; Meng, X.-J.; Kabalka, G. W. TL 1991, 32, 1945.
5. We thank Prof. Kabalka for providing experimental procedures for the synthesis of diisopropyl (E)- and (Z)-crotylboronates prior to publication.
6. Hoffmann, R. W.; Zeiss, H.-J. JOC 1981, 46, 1309.
7. Roush, W. R.; Ando, K.; Powers, D. B.; Palkowitz, A. D.; Halterman, R. L. JACS 1990, 112, 6339.
8. (a) Roush, W. R.; Banfi, L.; Park, J.-C.; Hoong, L. K. TL 1989, 30, 6457. (b) Brown, H. C.; Racherla, U. S.; Pellechia, P. J. JOC 1990, 55, 1868.
9. (a) Wuts, P. G.; Bigelow, S. S. JOC 1982, 47, 2498. (b) Roush, W. R.; Michaelides, M. R. TL 1986, 27, 3353. (c) Roush, W. R.; Michaelides, M. R.; Tai, D. F.; Lesur, B. M.; Chong, W. K. M.; Harris, D. J. JACS 1989, 111, 2984.
10. Brown, H. C.; Cole, T. E. OM 1983, 2, 1316.
11. Hoffmann, R. W.; Sander, T. CB 1990, 123, 145.
12. Wang, Z.; Meng, X.-J.; Kabalka, G. W. TL 1991, 32, 4619.

William R. Roush

Indiana University, Bloomington, IN, USA

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